Characterization of dihydropyridine binding sites in the rat brain: hypertension and age-dependent modulation of [H](+)-PN 200-110 binding

The properties of [³H]dihydropyridine (DHP), nitrendipine and (+)-PN 200-110, binding to rat cerebral membranes were investigated. In normotensive Wistar-Kyoto (WKY) adult rats, the highest densities of [³H]DHP binding sites were found in the hippocampus. Frontal cerebral cortex and hypothalamus had intermediate levels and no specific binding of [³H]DHP and [¹²⁵I]iodipine could be detected in the brainstem membranes and more precisely in the nucleus tractus solitarius and in the locus coeruleus. Changes in the maximal number of DHP binding sites (B_max) were observed in spontaneously hypertensive rats (SHR) and in old Sprague-Dawley rats. In adult SHR, there was a significant increase in theB_max values of [³H](+)-PN 200-110 binding in the hippocampus when compared to the values obtained in WKY. There was no difference in theB_max values between young (3 weeks) prehypertensive SHR and age-matched WKY. In senescent (26 months) Sprague-Dawley rats, theB_max values of [³H](+)-PN 200-110 binding were significantly reduced (30%) in the frontal cerebral cortex and the hippocampus, as compared with the number of DHP binding sites found in mature Sprague-Dawley rats (15 weeks).     

Spinal epidural lipomatosis: case reports, literature review and meta-analysis.

BACKGROUND CONTEXT: Symptomatic spinal epidural lipomatosis (SEL), a rare cause of spinal cord compression, has most often been associated with exogenous steroid use. PURPOSE: Identify four associations with SEL, correlate the associated groups with level of disease and compare treatment with outcome data in these groups. STUDY DESIGN/SETTING: Case reports of three patients and analysis of 104 cases from the literature. PATIENT SAMPLE: Three patients from the senior author's practice. OUTCOME MEASURES: Not applicable. METHODS: The authors report three new cases of SEL not associated with steroid use. They review all available English literature and present a table of all 104 reported cases. RESULTS: The clinical course of three new patients is reported. CONCLUSIONS: Associated conditions are exogenous steroid use, obesity, endogenous steroid excess, and some remain idiopathic. Although SEL is a rare condition, our review of the literature reveals many more reported cases than previously thought. With increased awareness of this condition and improved imaging techniques, further studies of this disease should be undertaken.     

Effectiveness of a Multidisciplinary Education Protocol in Children with Asthma (0-4 Years) in Primary Health Care

This paper describes the results of an asthma self-management protocol delivered to parents of children aged 0-4 years. The protocol was delivered by general practitioners (GPs), community nurses, asthma nurses, and doctors in child health centers. It consisted of 16 educational modules developed after an initial needs assessment of parents and a task analysis of primary care practitioners. The program was evaluated by means of an experimental design. Parents participating in the program had significantly more knowledge, a more favorable attitude toward asthma, and a higher self-efficacy score with respect to performing asthma self-management behaviors. Also, they reported performing self-management behaviors more frequently than parents in the control group. One-year follow-up results, which were collected for parents in the treatment group only, showed that the described changes were sustained. Further, the treatment group was found to have decreased its emergency and nonemergency use of the physician's office and to have a reduction in (reported) asthma severity. Process evaluation indicated that most modules were provided by the GPs to nearly all parents. After parents had read the modules at home, almost all the information was discussed in the next contact. GPs seldom referred patients to the community nurses, although this was suggested in the protocol.     

Altered steady state pharmacokinetics of levofloxacin in adult cystic fibrosis patients receiving calcium carbonate.

BACKGROUND: Levofloxacin is used in adult patients with cystic fibrosis but its pharmacokinetics is not well characterized in this population. Patients with cystic fibrosis use calcium routinely to prevent osteoporosis. A slower intestinal transit time is common in cystic fibrosis implying that the standard 2-h spacing of minerals and levofloxacin to prevent a chelation interaction may be insufficient. The objectives of this study were to characterize the steady state pharmacokinetics of oral levofloxacin 750 mg with and without 2-h spaced calcium carbonate in patients with cystic fibrosis compared to matched healthy volunteers. METHODS: In an open-label, randomized, cross-over study of five patients with cystic fibrosis and five age, sex, race, and serum creatinine matched healthy volunteers received 750 mg of oral levofloxacin alone daily for 5 days and the same dose of levofloxacin with 2-h spaced calcium carbonate supplementation 500 mg po thrice daily with meals in random sequence. Blood was collected for plasma assay of levofloxacin pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, and 24h after the fifth levofloxacin dose. RESULTS: There was no significant interaction in healthy volunteers, however, when cystic fibrosis patients were given levofloxacin with 2-h spaced calcium, the maximum plasma concentration (Cmax) decreased by 19% and time to Cmax increased by 37% (p<0.05). This difference in peak concentrations resulted in a lack of bioequivalence (Cmax geometric mean ratio 81.6%, 90% confidence intervals: 71.8%, 91.4%) even when levofloxacin and calcium supplements were spaced by the standard 2h administration instruction in patients with cystic fibrosis. CONCLUSIONS: These results indicate that multivalent cations such as calcium should be maximally separated from oral levofloxacin administration in adult patients with cystic fibrosis to prevent this drug interaction, thereby better optimizing antibiotic efficacy and decreasing the potential for resistance development.     

Outcomes of L1-L2 posterior lumbar interbody fusion with the Lumbar I/F cage and the variable screw placement system: reporting unexpected poor fusion results at L1-L2.

BACKGROUND CONTEXT: Posterior lumbar interbody fusion (PLIF) was introduced 50 years ago. The Lumbar I/F cage (DePuy Spine, Raynham, MA) was designed to enhance PLIF results. PLIF with the Lumbar I/F cage and posterior Variable Screw Placement System (VSP) has increased the success of fusion to nearly 100% at the four lowest lumbar levels, L2-L3 through L5-S1. Less commonly, PLIF is indicated for the L1-L2 level. Clinical-results of Lumbar I/F cage fusion and VSP at L1-L2 have-not been reported. PURPOSE: The purpose of this study is to report the functional outcomes, fusion rate, and complications related to PLIF with Lumbar I/F cage and VSP of L1-L2 STUDY DESIGN/SETTING: The setting is a retrospective, single-arm cohort study of consecutive PLIF surgical patients at a single center. PATIENT SAMPLE: A review of 373 of 425 patients who underwent PLIF with Lumbar I/F cage and VSP from 1999 to 2002 identified 12 patients who had PLIF with Lumbar I/F cage and VSP at L1-L2. Mean follow-up was 31 months (range 12-65 months). OUTCOME MEASURES: Clinical success was determined with a modified Prolo score evaluating pain, function, medication usage and economic status. Fusion success, determined by evaluation of plain radiographs, was defined by continuous bone bridging the fusion area with no lucencies. METHODS: The 12 patients were evaluated for clinical success and/fusion success at last follow-up. These results were compared with the results of the 373 patients reviewed, and historical groups of the original Investigational Device Exemption study and the 10-year follow-up study. RESULTS: Previous surgery was reported by 10 of 12 patients, with an average symptom-free period of 3 years after previous fusion and before presentation with severe symptomatology necessitating further surgery at L1-L2. Seven patients had clinical success (59%), and five patients were clinically unsuccessful (41%). This included zero excellent, 2 of 12 (15%) good, 5 of 12 (42%) fair, and 5 of 12 (42%) poor results. Fusion was successful in seven (58%) and failed in five patients (42%). Three failed fusions were associated with L1-L2 subsidence. Two patients required further revision for non-union. CONCLUSIONS: In 12 patients with L1-L2 fusion, we report an unexpected high rate of failed fusion and poor clinical outcome.     

Thymidylate synthase activity,folates, and glutathione system in head and neck carcinoma and adjacent tissues

Background. Head and neck squamous cell carcinomas (HNSCC) present variable aggressiveness and chemosensitivity. Because the glutathione (GSH) system and thymidylate synthase (TS) are involved in the resistance to the main drugs used in HNSCC (cisplatin and 5-FU), we studied these systems in tumors and normal mucosae. Methods. Tumor samples and normal adjacent mucosae were collected from 37 untreated HNSCC patients. GSH and glutathione S-transferase (GST) activity were assayed by spectrophotometry, whereas TS activity and folates were determined by radioassays. Results. Mean GSH levels were higher in tumors (15.2 ± 8.2 nmol/mg protein) than in mucosae (8.3 ± 4.1 nmol/mg protein) (p = 0.005, paired t test). GST activity was also higher in tumors (394 ± 194 nmol/min/mg protein) than in mucosae (261 ± 132 nmol/min/mg protein) (p = 0.0003). TS activity was markedly higher in tumors (9.2 ± 21.5 pmol/min/mg protein) compared to that of mucosae (0.9 ± 1.2 pmol/min/mg protein) (p = 0.0001). Folate levels in tumors and mucosae were similar (1.2 ± 1.1 and 0.8 ± 0.9 pmol/mg protein, respectively; p = 0.1, NS). In relation to clinical stage and tumor size, a statistical difference was found in GSH and GST values between tumors and mucosae for stage IV and T3/T4. The increase in tumor TS compared to that of mucosae was significant for all clinical stages, tumor sizes, and nodal involvement. Conclusions. These data enhance our understanding of the enzymatic systems involved in cisplatin and 5-fluorouracil (5-FU) resistance in HNSCC and normal mucosae and may help to elucidate tumor behavior and interpatient differences in drug sensitivity. © 1994 John Wiley & Sons, Inc.     

Treatment of an infected total hip replacement with the PROSTALAC system: Part 1: Infection resolution

INTRODUCTION: Infection after total hip replacement (THR) is a serious medical complication with significant negative ramifications for both the patient and the health care system. The prosthesis of antibiotic-loaded acrylic cement (PROSTALAC) was designed to treat the joint infection while maintaining functional movement in the hip. METHODS: We identified 28 patients treated for infected THR with the PROSTALAC system, by retrospective chart review. Preoperative and intraoperative cultures were taken to identify the causative organism. After PROSTALAC insertion, patients underwent at least 6 weeks of intravenous (IV) antibiotics. Prior to undergoing posttreatment cultures, patients were required to be antibiotic-free for a minimum of 6 weeks, with normal laboratory values. We defined resolution infection as retention of a joint prosthesis for a minimum of 2 years. RESULTS: Infection was identified in 28 patients in either the joint aspirate or intraoperative cultures. Of these patients, 2 failed to clear infection, requiring repeat PROSTALAC insertion. Two additional patients had positive 48-hour cultures post-second stage, treated with additional IV antibiotics. Retention of the post-PROSTALAC prosthesis is 100% at 2 years. CONCLUSION: PROSTALAC has acceptable infection resolution outcomes and appears effective for treating infected THR.