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Objective: The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. Background: Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. Methods: Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. Results: Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. Conclusions: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.

Poor diabetic control was found in nearly 50% of adolescents attending two paediatric clinics. Adolescents with well and poorly controlled diabetes differed in reported parental involvement in their diabetic regime. There was little association between glycaemic control and family functioning using the McMaster Family Assessment Device (FAD) whether rated by adolescent or a parent. Neither did sufferers with diabetes differ from families of matched community controls according to the FAD overall though the families of well controlled diabetics were more likely than the other two groups to score themselves in the unhealthy range on the subscale of global functioning.

The antimicrobial efficacy of four commercially available disinfectants (Haz-tabs, chlorhexidine, Virkon and CJ Algisept Spray) was investigated. It was shown that all were effective in decontaminating the impressions whilst those placed only in sterile water, used as a control, showed variable levels of bacterial growth. Moreover, alginate appeared to carry significantly higher numbers of bacteria than addition cured silicone rubber.

The murine multiple drug resistance (mdr) gene, mdr1a, encodes a 170-kDa transmembrane protein that is expressed in many tissues including intestinal epithelial cells, a subset of lymphoid cells and hematopoietic cells. We report that mdr1a knockout (mdr1a-/-) mice are susceptible to developing a severe, spontaneous intestinal inflammation when maintained under specific pathogen-free animal facility conditions. The intestinal inflammation seen in mdr1a-/- mice has a pathology similar to that of human inflammatory bowel disease (IBD) and is defined by dysregulated epithelial cell growth and leukocytic infiltration into the lamina propria of the large intestine. Treating mdr1a-/- mice with oral antibiotics can both prevent the development of disease and resolve active inflammation. Lymphoid cells isolated from mice with active colitis are functionally reactive to intestinal bacterial Ags, providing evidence that there is enhanced immunologic responsiveness to the normal bacterial flora during IBD. This study is the first description of spontaneous colitis in a gene knockout mouse with an apparently intact immune system. This novel model of spontaneous colitis may provide new insight into the pathogenesis of IBD, the nature of dysregulated immune reactivity to intestinal bacterial Ags, and the potential functional role of mdr genes expressed in the cells and tissues of the colonic microenvironment.

Analysis of statewide survey data revealed that 22.5% of individuals with mental retardation who were served by the Oklahoma mental retardation system were receiving antipsychotic medication. Anxiolytic medications were prescribed for 9.3%, and antidepressants were prescribed for 5.9%. Higher levels of medication use were found in institutional settings and Intermediate Care Facility settings.

In a 5-year prospective study, computed tomographic (CT) morphometry of the lumbosacral vertebral canal was performed on 42 large-breed dogs (21 controls and 21 dogs with lumbosacral stenosis). Dogs were allotted to 4 groups. Group 1 (n = 13) consisted of cadaver specimens obtained from dogs that died or were euthanatized for reasons unrelated to the spine; group 2 (n = 8) consisted of live dogs with no history of clinical signs related to the spine and with normal neurologic examination findings; group 3 (n = 10) consisted of dogs with surgically confirmed lumbosacral stenosis; and group 4 (n = 11) consisted of dogs with suspected lumbosacral stenosis that were managed conservatively. The CT scans were performed, using 5-mm contiguous slices obtained perpendicular to the vertebral canal, from the midbody of the 5th lumbar vertebra through the caudal endplate of the sacrum (L5-S3). Lumbosacral lordosis was minimized in all dogs by positioning them in dorsal recumbency with the hind limbs flexed. A tuberculin syringe calibration phantom was placed within the scanning field of view, parallel to the axis of the spine. In each dog, 11 CT slice locations within the lumbosacral spine were evaluated. At each slice location, sagittal plane diameter, dorsal plane diameter, and transverse area of the vertebral canal, vertebral body, and calibration phantom were measured, using the CT computer's software programs for distance and area calculation. Window/level settings were constant, and all measurements were made by the same operator (JCJ). Accuracy of calibration phantom CT measurements was 100% for sagittal and dorsal plane diameter and was 85% for transverse area.(ABSTRACT TRUNCATED AT 250 WORDS)

Although sphenoidal electrodes are widely used to detect epileptiform activity, there is no agreement on an optimal target to which electrodes should be aimed. The purpose of this study was to determine whether fluoroscopic guidance is a reliable method for placing electrodes directly below the foramen ovale and whether such positioning enhances their capacity to detect epileptiform activity when compared to similar electrodes placed blindly into the infratemporal fossa. We examined the surface/sphenoidal EEG recordings of 17 patients with intractable partial seizures of anterotemporal origin, after fluoroscopically placed sphenoidal electrodes (FPSE) had been inserted to lie just below the foramen ovale. A criterion for eligibility was a previous prolonged video/EEG monitoring with blindly placed sphenoidal electrodes (BPSE) that failed to detect seizures with a focal onset. No blindly placed electrode, for which there was radiographic documentation, reached the foramen ovale. Fluoroscopic guidance assured accurate targeting. FPSE detected a unilateral anterotemporal interictal focus in four patients in whom BPSE had failed to record any interictal spikes and detected bitemporal independent interictal foci in one patient in whom BPSE had identified only unilateral spikes. In nine other patients, the spike count obtained with FPSE recordings increased by100% when compared to that obtained with BPSE recordings. FPSE recorded seizures with an anterotemporal focal onset pattern in 10 patients in whom BPSE had recorded seizures with a regional, lateralized, or nonlocalized onset pattern. In nine of these 10 patients, this was adequate to recommend surgery and avoid invasive monitoring. Fluoroscopic guidance assures accurate targeting of the foramen ovale. When compared to BPSE, FPSE resulted in better detection of interictal and ictal epileptiform activity of mesial-basal-temporal origin.

We have used three methods to study the formation and repair of intrastrand adducts and interstrand cross-links in the DNA of Chinese hamster ovary cells induced by the anticancer drug cis-diamminedichloroplatinum II (cisplatin). Using atomic absorption spectroscopy, we found that 21% of the total genomic cisplatin adducts were removed at 8 h and 42% at 24 h. We used ABC excinuclease digestion, coupled with out previously reported methodology to quantify DNA in specific genomic regions. These adducts were removed faster in the transcribed dihydrofolate reductase and c-myc genes compared to a noncoding fragment, a region containing the little or nontranscribed c-fos oncogene, and to the overall genome. Interstrand cross-links in specific sequences were quantified by Southern hybridization of denatured-renatured DNA separated on a neutral gel. We found that cross-links were removed more efficiently from the gene regions than intrastrand adducts and, at high levels of cross-linking, removal was similar from transcribed and from nontranscribed regions.

The effect of plasma from normotensive and hypertensive subjects on the binding of [3H]ouabain on human erythrocytes was investigated. The binding of [3H]ouabain on human erythrocytes was saturable and highly specific; linear Scatchard plots indicated the presence of a single type of binding site. Human plasma decreased the binding of [3H]ouabain on its receptor to a greater extent than could be accounted for by the plasma potassium concentration. The level of this circulating ouabainlike factor (or factors) was quantitated using a radioreceptor assay. Plasma from 22 hypertensive subjects (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 90 mm Hg) displayed higher levels than that from 24 normotensive subjects; furthermore there was a positive and significant correlation (r = 0.42, n = 46, p less than 0.004) between the ouabainlike content and the individual subject's systolic blood pressure. The receptor assay described is relatively simple and should be useful for further work on the nature and clinical importance of the endogenous ouabainlike factor.

The planning of treatment for patients with gynaecological cancer undergoing combined intracavitary and external beam irradiation at the Royal Marsden Hospital is described. The purpose of the external beam irradiation is to increase the dose to the parametria and pelvic nodes since these tissues are generally too far from the intracavitary 137Cs sources to receive a tumoricidal dose. The treatment policy and problems of dosimetry are discussed. The main problem is to combine the two modes of radiotherapy so as to ensure an adequate dose to the required regions and to afford protection to previously irradiated areas. The method of computing the dose distribution from the intracavitary 137Cs sources is described and also how this distribution is used to design protective absorbers for use with the external beam therapy. Different shapes of absorbers are required for cobalt units and linear accelerators because of the different beam characteristics. The way in which these are designed for individua...

Abnormalities of calcium binding and calcium transport in cells from hypertensive subjects or animals have been previously described. Total cell sodium is reported to be increased in white blood cells from hypertensive subjects; thus by analogy with Blaustein's proposal for the vascular smooth muscle cell, mononuclear leucocyte cytosolic calcium might be increased via a reduction of the Na-Ca exchange. Using the fluorescent calcium indicator, quin 2, cytosolic calcium was measured in mononuclear leucocytes from 22 hypertensive and 19 normotensive subjects. There was no significant difference between the mononuclear leucocyte cytosolic calcium level in the two groups. Incubation of the cells with 10(-4) M ouabain reduced 86 rubidium (86Rb) uptake by 80% of the control value but failed to alter cytosolic calcium. These findings are consistent with a minimal role of the Na-Ca exchange in the mononuclear leucocyte and may explain why the cytosolic calcium was not increased in hypertension despite the previous reports of increased total cell sodium in white blood cells.

A prospective, randomized clinical trial of adjuvant treatment of 312 stage II breast cancer patients with use of chemotherapy, antiestrogen therapy, and immunotherapy is reported after 72 months of follow-up. The stratification of patients was based on nodal involvement and estrogen receptor (ER) assay of the primary tumors. Findings at 72 months indicate that antiestrogen therapy (tamoxifen, Nolvadex) added to chemotherapy with cyclophosphamide (Cytoxan), methotrexate, and fluorouracil (5-Fluorouracil) (CMF) resulted in significant delayed recurrence in ER-positive postmenopausal patients, ER-positive patients with four or more positive nodes, and ER-positive patients with tumors greater than 3 cm in diameter. The addition of nonspecific immunotherapy with bacillus Calmette-Guerin had no effect on disease-free survival. ER and progesterone receptor measurements in patients with primary breast cancer provide valuable prognostic information on subsequent recurrence and overall survival and should be documented in future clinical trials.

A prospective, randomized clinical trial of adjuvant treatment of 318 stage II breast cancer patients, using chemotherapy, the antiestrogen tamoxifen, and immunotherapy is reported at 48 months follow-up. Women whose primary tumors have no estrogen receptors fall into a significantly poorer prognostic group than those whose tumors contain estrogen receptors. None of the adjuvant regimens appeared to offer any clear-cut advantage for the estrogen receptor negative patients. Those women whose primary tumor contains estrogen receptors appear to be in a prognostically favorable group, when their treatment regimen included the antiestrogen, tamoxifen. The adjuvant use of BCG immunotherapy does not appear to offer additional benefit, but the follow-up period of these treated patients is too brief to be conclusive. A longer period of observation is needed to determine whether this systemic treatment in estrogen receptor positive patients is preventing recurrence or merely delaying it.

A prospective, randomized clinical trial of three treatment regimens: (1) Cytoxan, methotrexate, and 5-fluorouracil (CMF), (2) CMF plus the antiestrogen drug, tamoxifen (CMFT), and (3) CMFT plus bacillus Calmette-Guerin (BCG) vaccinations in women with stage 22 breast cancer is reported. All patients underwent mastectomy and estrogen receptor (ER) analysis was performed. The results of this study show that patients with ER- tumors have recurrences more rapidly and have a higher mortality rate than patients with ER+ tumors (P less than 0.0001). In ER+ patients CMFT treatment is more effective in delaying recurrence than CMF alone at 33 months (P = 0.0176). This effect appears to be occurring in both premenopausal and postmenopausal women. In ER- patients the recurrence rate is high, and there is no significant difference among the three treatment groups. In premenopausal patients treated with CMF alone, however, ER- patients recur more rapidly than ER+ patients (P = 0.0313) and suggests that the effect of CMF may be related to the suppression of ovarian function. These findings have demonstrated a significant role for the use of antiestrogen therapy in patients with state II, ER+ breast cancer.

The results of adjuvant chemotherapy (CMF), endocrine therapy (t), and immunotherapy (BCG) in 318 women who had undergone mastectomy for Stage II breast cancer are reported after 45 months of life table analysis. CMFT therapy was found to be more effective than CMF alone in increasing recurrence-free survival. This beneficial effect appears to be limited to patients with estrogen receptor-positive tumors (ER+). Patients with estrogen receptor-negative tumors (ER-) (3 fmol/mg) have increased recurrence rates and higher mortality.

The case report presented herein involves a granular cell tumor of the vulva, an uncommon site, with unusual clinical characteristics.