Tissue plasminogen activator mediated blood-brain barrier damage in transient focal cerebral ischemia in rats: relevance of interactions between thrombotic material and thrombolytic agent

Thrombolysis with tPA for acute ischemic stroke is associated with an increased risk of intracerebral hemorrhage. We investigated the impact of thrombolysis with tPA on the blood-brain barrier in a suture occlusion model in rats. Cerebral ischemia was performed for 2 h followed by 22 h of reperfusion. Treatment groups received either saline (A), 10 mg/kg bw rtPA (B) or "activated" rtPA (ArtPA, C, rtPA with in vitro clot contact). Blood-brain-barrier damage assessed by Evans blue extravasation as a permeability marker was significantly enhanced in basal ganglia of group C compared to groups A or B. Likewise was the upregulation of MMP-9. Interestingly, results of the rtPA and saline group showed only minor and not statistically significant differences. The results of the present study indicate a major role for thrombus-thrombolytic interaction in focal cerebral ischemia with subsequent increased BBB permeability.     

Acquired pendular nystagmus: its characteristics, localising value and pathophysiology

Investigations were made of 16 patients with acquired pendular nystagmus and a further 32 cases reported in the literature were reviewed. Amongst our own patients two thirds had multiple sclerosis, almost one third a cerebrovascular accident or angioma and two had optic atrophy with squint. The nystagmus took forms which could be monocular or binocular, conjugate or disconjugate and could involve movements about single or multiple axes. Spectral analysis was used to characterise the amplitude and frequency of the movements and to estimate the degree of relationship (coherence) between movements of the two eyes or between movements of one eye about several axes. The oscillations ranged in frequency from 2·5 Hz to 6 Hz, with typical amplitudes between 3° and 5°. In a given patient all oscillations, regardless of plane, were highly synchronised. Somatic tremors of the upper limb, face and palate associated with the nystagmus were often at similar frequencies to the eye movement. The other ocular signs common to all our patients were the presence of squint with failure of convergence. Most patients also had skew deviation or internuclear ophthalmoplegia or both. The major oculomotor systems, that is, saccades, pursuit, optokinetic and vestibulo-ocular reflexes could be intact. It is inferred that the mechanism responsible for the pendular nystagmus lies at a level which is close to the oculomotor nuclei so that it can have monocular effects but is not part of the primary motor pathways. It is possible that this mechanism normally subserves maintenance of conjugate movement and posture of the eyes. The periodicity of the nystagmus is likely to arise from instability in a certain type(s) of neurone, for the associated somatic tremors have similar characteristics and yet involve very different neuronal muscular circuitry. Prognosis for cessation of the nystagmus is poor. In five patients with multiple sclerosis it was suppressed by intravenous hyoscine with, however, unacceptable subsequent side effects.     

Sinonasal myxoma: a pediatric case

The authors report a case of a rare facial myxoma arising from the maxillary sinus in a 20-month-old child. The diagnosis was confirmed by a biopsy, and the patient underwent a partial maxillectomy to achieve a total resection of the mass due to the locally aggressive nature of the lesion. Myxomas should be differentiated from malignant sarcomas, in particular embryonal rhabdomyosarcoma, which can arise from the same location and require multimodality therapy consisting of surgery, irradiation, and chemotherapy.     

Evaluation of serum S100B as a surrogate marker for long-term outcome and infarct volume in acute middle cerebral artery infarction

BACKGROUND: An easily accessible and valid surrogate marker for interventional stroke trials is needed. OBJECTIVE: To investigate the usefulness of various S100B serum measures to predict long-term outcome and infarct volume in patients with acute stroke. DESIGN: Inception cohort study. SETTING: Tertiary care university hospital. PATIENTS: Thirty-nine patients (mean +/- SD age, 69.1 +/- 11.5 years) with acute nonlacunar middle cerebral artery infarction presenting less than 6 hours after symptom onset. MAIN OUTCOME MEASURES: Functional outcome 6 months after stroke (modified Rankin scale score) and final infarct volume on day 7 by means of standardized volumetry of brain images. Serum S100B level was determined at hospital admission and 24, 48, 72, 96, 120, and 144 hours after symptom onset. RESULTS: Single S100B measures obtained 48 and 72 hours after stroke onset demonstrated the highest Spearman rank correlations with modified Rankin scale scores (rho = 0.68 and rho = 0.67, respectively; P<.001) and infarct volume (rho = 0.95 and rho = 0.94, respectively; P<.001). A 48-hour S100B value of 0.37 microg/L or less revealed a sensitivity of 0.87 and a specificity of 0.78 in predicting an independent functional outcome. In a multivariate model, S100B emerged as an outcome predictor that was independent of age, sex, stroke severity, etiology, lesion side, and risk factors. CONCLUSIONS: Single S100B values obtained 48 and 72 hours after stroke onset provide the highest predictive values with respect to functional outcome and infarct volume in nonlacunar middle cerebral artery infarction. More complex measures of the S100B kinetic (ie, area under the curve or peak value) were not superior. Therefore, these single S100B measures appear to be useful surrogate end points in acute interventional stroke trials.     

The value of a noninvasive diagnostic approach to mediastinal masses

BACKGROUND: Mediastinal tumors show a wide variability, and therefore, a standardized diagnostic and therapeutic workup is instrumental. We subdivided mediastinal tumors into nonlymphatic mediastinal tumors (NLMTs), most of which require surgical resection without need of preoperative histology, and mediastinal lymphadenopathy (MLA), requiring surgical biopsy for exact histologic classification. We investigated the accuracy of noninvasive diagnostic studies distinguishing between the two groups of MLA and NLMT. METHODS: A retrospective analysis was performed on patients who had previously undergone surgery on mediastinal tumors. Their data were statistically analyzed (chi2 test, logistic regression analysis), and the values of medical history, physical examination, laboratory tests, and computerized tomography scan discriminating between MLA and NLMT were assessed. RESULTS: Out of 299 patients included in the study, 242 (80.9%) had MLA and 57 (19.1%) had NLMT. Sensitivity and specificity of noninvasive investigations for differentiation of MLA and NLMT were 98.2% and 86.0%, respectively. Whereas the prevalence of thoracic symptoms such as shortness of breath, cough, or chest pain was similar in both groups (MLA, 165 [69.3%]; NLMT, 41 [69.5%]; p = 0.98), systemic symptoms, including fever, night sweats, or weight loss (MLA, 110 [49.8%]; NLMT, 17 [29.3%]; p < 0.01), and signs of inflammation, such as c-reactive protein, erythrocyte sedimentation rate, and leukocytosis (MLA, 202 [85.6%]; NLMT, 34 [57.6%]; p < 0.001), were significantly more common in MLA. CONCLUSIONS: Noninvasive diagnostic procedures, including medical history, physical examination, laboratory tests, and computerized tomographic scan, are highly sensitive in detecting MLAs that should undergo surgical biopsy. Our data suggest confirming all suspected NLMTs by fine needle aspiration (FNA) biopsy before surgery.     

Prevention of heterocyclic amine-induced DNA damage in colon and liver of rats by different lactobacillus strains

The aim of the present study was to investigate the impact of four different lactobacillus (LB) strains, namely Lactobacillus bulgaricus 291, Streptococcus thermophilus F4, S.thermophilus V3 and Bifidobacterium longum BB536, which are used for the production of yogurt, on the DNA-damaging effects of heterocyclic aromatic amines (HCAs). Male F344 rats were treated orally with HCA mixtures containing 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline, 2-amino-9H-pyrido[2,3-b]indole and 2-amino-3-methyl-3H- imidazo[4,5-f]quinoline, which were representative of the HCA contents found in fried beef ('beef mix') and chicken ('chicken mix'). Suspensions of LB were given by gavage to the animals simultaneously with and at different time periods before administration of the HCAs. Subsequently, the extent of DNA migration was measured in colon and liver cells in single cell gel electrophoresis (SCGE) assays. All four strains caused complete inhibition of DNA damage induced with beef mix after administration of 1 x 1010 LB cells/animal, whereas with chicken mix only marginal (non-significant) effects were seen. The inhibition of beef-induced DNA damage was dose dependent and was still significant when 1 x 107 cells/animal were administered. Kinetics studies showed that the protective effects were still significant when LB was given 12 h before the beef mix. A comparison of the present results with chemical analytical data from in vitro experiments suggests that the strong reduction in DNA migration seen in the animals can be only partly explained by direct binding effects. The results of the present study show that LB are highly protective against the genotoxic effects of HCAs under conditions which are relevant for humans and provide a possible explanation for the reduced colon cancer rates observed in some studies in individuals with either high LB counts in their feces or with a high consumption of LB-containing foods.     

Radiology of the orbital apex

The orbital apex, formed by the superior orbital fissure and optic canal, is the cross-road between the orbit and the intracranial structures. Pathological processes may extend intracranially via the superior orbital fissure and vice versa. In addition to intrinsic soft tissue lesions, various pathological processes may involve the surrounding osseous anatomy. Malignant lesions arising from adjacent structures or from haematogeneous metastasis may also infiltrate this region.     

Optimal treatment for the technically resectable squamous cell carcinoma of the supraglottic larynx.

The charts of 431 patients with squamous cell carcinoma of the supraglottic larynx observed at the M. D. Anderson Hospital between January, 1954, and June, 1971, were analyzed. This study is concerned with those patients who had a technically resectable lesion. Emphasis is directed to the analysis of the effectiveness of primary irradiation instead of partial laryngectomy for those lesions which are technically suitable for a partial resection and to define the groups of patients which are best treated by combining surgery and planned postoperative irradiation. One hundred forty-seven patients with T₁ and T₂ lesions, selected exophytic T₃ lesions of the suprahyoid epiglottis and aryepiglottic folds and some selected exophytic T₄ lesions of the suprahyoid epiglottis received irradiation for their laryngeal lesion. A satisfactory control of the laryngeal disease has been obtained with preservation of a normal voice ranging from 88.5 percent for T¹ lesions to 60 percent for T₄ lesions. Comparing the groups of patients who had surgery alone or postoperative irradiation an NED rate of 63 percent was found in the latter group which is clearly superior to the 37 percent found in the surgery only group. There is no difference for the five-year NED rates, because the patients who had surgery and postoperative irradiation had more advanced neck disease which is a cause for distant metastases. The incidence of recurrences above the clavicles is clearly less in the patients having had surgery and postoperative irradiation than in those who had surgery alone. Correlating in the two groups, surgery only and surgery followed by planned irradiation, the surgical staging of the neck metastases with recurrences above the clavicles within 24 months after treatment, it was found that the planned combined treatment has reduced the recurrence rate from 45 percent to 15 percent in the N₂ and N₃ patients. Postoperative irradiation should be given routinely after resection for all T₄ lesions and for any T₃ lesion which extends to the pharyngeal wall(s), vallecula, base of tongue, and pyriform sinus. Postoperative irradiation should also be given for any patient whose nodal classification is greater than N₁. Irradiation should be given within six weeks (preferably three to four weeks) after the surgical procedure. To achieve this goal, the operation need only remove grossly detectable disease.