In vitro and in vivo efficacy of non-psychoactive cannabidiol in neuroblastoma.

BACKGROUND: Neuroblastoma (nbl) is one of the most common solid cancers in children. Prognosis in advanced nbl is still poor despite aggressive multimodality therapy. Furthermore, survivors experience severe long-term multi-organ sequelae. Hence, the identification of new therapeutic strategies is of utmost importance. Cannabinoids and their derivatives have been used for years in folk medicine and later in the field of palliative care. Recently, they were found to show pharmacologic activity in cancer, including cytostatic, apoptotic, and antiangiogenic effects. METHODS: We investigated, in vitro and in vivo, the anti-nbl effect of the most active compounds in Cannabis, Δ(9)-tetrahydrocannabinol (thc) and cannabidiol (cbd). We set out to experimentally determine the effects of those compounds on viability, invasiveness, cell cycle distribution, and programmed cell death in human nbl SK-N-SH cells. RESULTS: Both compounds have antitumourigenic activity in vitro and impeded the growth of tumour xenografts in vivo. Of the two cannabinoids tested, cbd was the more active. Treatment with cbd reduced the viability and invasiveness of treated tumour cells in vitro and induced apoptosis (as demonstrated by morphology changes, sub-G1 cell accumulation, and annexin V assay). Moreover, cbd elicited an increase in activated caspase 3 in treated cells and tumour xenografts. CONCLUSIONS: Our results demonstrate the antitumourigenic action of cbd on nbl cells. Because cbd is a nonpsychoactive cannabinoid that appears to be devoid of side effects, our results support its exploitation as an effective anticancer drug in the management of nbl.

Post-lymphangiographic computed tomography in chylothorax after esophagogastrectomy: a case report.

Chylothorax is a rare complication of thoracic surgery. Lymphangiography has long been considered to be the standard of reference for diagnosis and post-treatment evaluation while the role of post-lymangiographic CT is debated. We report a case of chylothorax in a 68-year-old male following esophagogastrectomy for which conservative treatment and thoracic duct ligation failed. Lymphangiography performed after these attempts revealed persistent thoracic duct leakage into the right pleural space. Subsequent non-contrast CT and reformatted images clearly depicted the sources of leakage, and this documentation targeted direct percutaneous treatment. Unfortunately, the lack of access precluded the planned percutaneous CT-guided embolization of the thoracic duct. Nevertheless, this case suggests that post- lymphangiographic CT can serve as a value-added modality in the evaluation and potential treatment of chylothorax.

Treatment of chronic childhood asthma with beclomethasone dipropionate aerosols: II. Effect on pituitary-adrenal function after substitution for oral corticosteroids.

The effects of beclomethasone, dipropionate aerosol (DBA) (400 microgram/day) on clinical course, pulmonary function, and pituitary-adrenal function was studied in 34 steroid-dependent asthmatic children. Asthma severity was assessed by daily symptom and medication scores, peak flow measured three times a day, and weekly spirometry. Pituitary-adrenal function was evaluated by diurnal cortisol levels, cortisol responses to intravenous (IV) corticotropin (ACTH), and steroid responses to IV metyrapone. After 12 weeks of BDA therapy, 30 of 34 patients no longer required prednisone. Mean weekly symptom and medication scores and the number of attacks decreased significantly (P less than .01)). A significant improvement was demonstrated in the patients' peak flow (P less than .01), forced expiratory volume in one second, and maximum midexpiratory flow rates (P less than .01). Thirty of the 34 patients initially had abnormal metyrapone responses, 28 had abnormal diurnal cortisol levels, whereas only 14 had abnormal IV ACTH response tests. Although significant improvement was noted in the mean metyrapone and diurnal cortisol tests, only partial recovery of pituitary-adrenal function was observed in 20 patients, complete recovery in 5, and no change in 9. BDA was found to be therapeutically superior to oral steroids in the group of steroid-dependent asthmatic children and produced no serious adverse effects.

Chemical breakdown of technetium-99m DTPA during nebulization.

Aerosols of 99mTc diethylenetriaminepentaacetic acid ([99mTc]DTPA) used for measuring lung permeability and lung ventilation require a radioaerosol delivery system to produce an aerosol with reproducible size and radiochemical purity. To test how well nebulizers meet this requirement, radiochemical purity of aerosols produced with a jet and an ultrasonic nebulizer was evaluated. The activity median aerodynamic diameter (AMAD) and geometric standard deviation (sigma g) of radioaerosols were 0.46 micron (sigma g = 1.6) for the jet nebulizer and 0.70 micron (sigma g = 1.7) for the ultrasonic nebulizer. Paper and liquid chromatographic assays were obtained on the [99mTc]DTPA aerosol solute produced with each nebulizer. The results of these tests showed major differences in radiochemical purity. Aerosols produced in the jet nebulizer consistently showed greater than 90% of the radioactivity bound to the DTPA ligand whereas aerosols produced in the ultrasonic nebulizer showed less than 10% of the radioactivity bound to DTPA. The results support the need to test radiochemical purity of aerosols before using an aerosol nebulizer for pulmonary imaging and clearance studies.

Pulmonary vascular disease after systemic-pulmonary arterial shunt operations.

More than 1,100 patients underwent a systemic-pulmonary arterial shunt operation at the Children's Memorial Hospital, Chicago, from 1946 to 1974. Of these patients, 294 were studied to assess the presence of pulmonary vascular disease and the time of its occurrence after surgery. They were selected either because lung tissue was available for histologic grading of pulmonary vascular disease (114 patients) or because hemodynamic studies were performed after the shunt operation (180 patients). The shunts, all patent at the time of the study, ranged in duration from 1 month to 23 years. After a subclavan-pulmonary arterial shunt (75 patients) there was little evidence of advatients) pulmonary vascular disease in either histologic C2 of 25 patients) or hemodynamic (1 of 50 patients) studies. After an aortic-pulmonary arterial shunt (44 Waterston, 175 Potts) there was small likelikhood of advanced pulmonary vascular disease with a shunt duration of less than 5 years (1 of 35 histologic, 0 of 27 hemodynamic studies). With a shunt duration of more than 5 years the incidence of advanced pulmonary vascular disease increased significantly (15 of 54 histologic, 17 of 103 hemodynamic studies). A mean pulmonary arterial pressure of 50 mm Hg or greater strongly suggests the presence of advanced pulmonary vascular disease. When a systemic-pulmonary arterial shunt has provided effective palliation with decreased pulmonary pressure there is small likelihood that advanced pulmonary vascular disease will develop, even with a long shunt duration of 20 to 25 years.

The diffusion of innovations in hospitals. Some econometric considerations.

Empirical studies of the diffusion of innovations have not addressed adequately econometric problems that are characteristic of such analyses. Reanalysis of data for five innovations using an estimator with desirable statistical properties results in a considerably revised estimate of the impact of prospective reimbursement on diffusion.

Variations in cognitive, perceptual, and psychomotor abilities across the working life span: examining the effects of race, sex, experience, education, and occupational type.

Cognitive, perceptual, and psychomotor abilities were examined across the working life span for different racial groups, taking into consideration sex, job experience, education, and occupational type. Data included scores on all subtests of the General Aptitude Test Battery for White, Black, and Hispanic employees. Age and sex generally accounted for a relatively small percentage of the variance in ability test scores when experience, education, and occupational type were controlled. Race accounted for a substantial amount of variance in test performance, even after controlling for education, experience, occupational type, and age. Findings are discussed in terms of the potential for specific experiences and continuing education to affect the maintenance of abilities at later points in the life span for all racial groups.

Ratings of managerial skill requirements: comparison of age- and job-related factors.

This article examines how individual characteristics (age, experience) and organizational characteristics (department, level) influence the skill requirements rated as being important for managerial jobs. One hundred ninety-seven managerial employees completed a survey composed of 20 skill dimensions pertinent to supervisory positions in the mining industry. Organizational level and departmental affiliation were correlated with job skill importance ratings. Ratings of skill importance were also correlated with the age of the person being rated, years of experience, and the age of the rater. As predicted, correlations with ratee age varied across different skill dimensions. This study has implications for fair employment practices to the degree that raters base evaluations of a job on the age of incumbents vs. job relevant characteristics.

Resurfacing of the patella in total knee arthroplasty. A prospective, randomized, double-blind study.

During a two-year period, eighty-nine patients who were scheduled to have a total knee arthroplasty for the treatment of degenerative osteoarthrosis were randomly assigned to one of two groups: resurfacing of the patella or retention of the patella. All patients received the same posterior cruciate-sparing prosthesis, and all operations were performed by, or under the direct supervision of, one of us. Three patients died in the early postoperative period. The remaining eighty-six patients (118 knees; fifty-eight that had had resurfacing of the patella and sixty that had not) formed the study group. They were followed for a mean of thirty months (range, twenty-four to forty-four months). Evaluation was performed with use of the clinical scoring system of The Knee Society, a patient-satisfaction questionnaire, specific questions regarding patellofemoral symptoms and function, and radiographs. All clinical evaluations were performed by the same research nurse, without the involvement of a physician, in a blinded manner (neither the nurse nor the patient had knowledge of whether the patella had been resurfaced). Preoperatively, the mean Knee Society score, on a scale ranging from 0 to 200 points, was 89.7 points (range, 33 to 132 points); postoperatively, this score improved to a mean of 172.7 points (range, 98 to 200 points). With the numbers available for study, we could detect no significant difference between the knees that had had patellar resurfacing and those that had not with regard to the over-all score (p = 0.63), the subscore for pain (p = 0.56), or the subscore for function (p = 0.77). We also could detect no difference between the treatment groups, with the numbers available, with regard to patient satisfaction or the responses to questions involving the function of the patellofemoral joint, including the ability to exit from an automobile, to rise from a chair, and to climb stairs. Thirty-two patients had bilateral total knee replacement with resurfacing of the patella in one knee and retention of the patella in the other. These patients expressed no clear preference for either knee. Eight (13 per cent) of the sixty knees that had not had resurfacing were painful anteriorly compared with four (7 per cent) of the fifty-eight that had; this was not a significant difference (p = 0.38), with the numbers available. The anterior pain that was noted postoperatively was predominantly of new onset; it had not been observed preoperatively in three of the four knees that had had resurfacing or in four of the eight that had not. No additional treatment options were offered to the patients who had anterior pain in the knee after resurfacing. However, six (10 per cent) of the sixty knees that had not had resurfacing had it subsequently, because of anterior pain in the knee, after the twelfth postoperative month (range, fifteen to thirty-nine months). The pain decreased in four of these knees. Thus, total knee arthroplasty with retention of the patella yielded clinical results that were comparable with those after total knee arthroplasty with patellar resurfacing, but it was associated with a 10 per cent prevalence of the need for subsequent resurfacing. The prevalence of anterior pain after total knee arthroplasty was not influenced by whether or not the patella had been resurfaced. The postoperative clinical scores, the postoperative development of anterior pain, and the need for subsequent resurfacing were not predicted by the presence of preoperative anterior pain, obesity, or the grade of chondromalacia observed intraoperatively. Because of the short duration of follow-up, these results should be considered preliminary. Additional follow-up is planned.

Patellar resurfacing in total knee arthroplasty. A prospective, randomized, double-blind study with five to seven years of follow-up.

BACKGROUND: Whether to resurface the patella during a primary total knee arthroplasty performed for the treatment of degenerative osteoarthritis remains a controversial issue. Parameters that have been suggested as being useful in guiding this decision include patient height and weight, the presence of anterior knee pain preoperatively, and the grade of chondromalacia encountered intraoperatively. The purpose of this study was to determine whether these parameters were predictive of the clinical result following total knee arthroplasty with or without patellar resurfacing. METHODS: Eighty-six patients (118 knees) undergoing primary total knee arthroplasty for the treatment of osteoarthritis were enrolled in a prospective, randomized, double-blind study. All patients received the same posterior-cruciate-sparing total knee prosthetic components. Patients were randomized to treatment with or without resurfacing of the patella. Evaluations consisted of the determination of a Knee Society clinical score, the completion of a patient satisfaction questionnaire, specific questions relating to patellofemoral symptoms, and radiographs. Sixty-seven patients (ninety-three knees) were followed for a minimum of five years (range, sixty to eighty-four months; average, 70.5 months). RESULTS: With the numbers available, there was no significant difference between the groups treated with and without resurfacing with regard to the overall Knee Society score or the pain and function subscores. Obesity, the degree of patellar chondromalacia, and the presence of preoperative anterior knee pain did not predict postoperative clinical scores or the presence of postoperative anterior knee pain. CONCLUSIONS: The occurrence of anterior knee pain could not be predicted with any clinical or radiographic parameter studied. On the basis of these results, it seems likely that postoperative anterior knee pain is related either to the component design or to the details of the surgical technique, such as component rotation, rather than to whether or not the patella is resurfaced.

Endovascular and open surgical treatment of brachiocephalic arterial disease.

The treatment of occlusive lesions in the innominate, subclavian, and axillary arteries has, until recently, been entirely surgical. Recently, advances in endovascular technologies have provided an alternative means of therapy. The advent of balloon angioplasty has resulted in some turmoil between medical specialties regarding patient selection and acceptable applications. Innovations in imaging, guidewire, catheter, stent, and balloon technology allow one to obtain percutaneous access and perform therapeutic procedures in a relatively safe manner. However, the excellent and time-tested results of surgery remain a standard for developing new procedures. Despite the appeal of less invasive techniques, the morbidity, mortality, and durability of novel treatments must equal or exceed those standards set by surgical procedures. Proponents of the endovascular options must familiarize themselves with advantages and disadvantages of surgical procedures. In a similar manner, surgeons have an obligation to understand the less invasive technologies as well. The clinician must uphold the best interests of the patient as a fundamental factor in the determination of a particular form of therapy. This paradox is well illustrated by consideration of occlusive lesions in the upper extremity.

MRI meningeal enhancement with intracranial hypotension caused by lumbar puncture.

A 12-year-old girl with recent history of pseudotumor cerebri developed severe postural headache due to intracranial hypotension after lumbar puncture. Meningeal enhancement and thickening were demonstrated on magnetic resonance imaging. Repeated imaging 3 months later disclosed no abnormalities. This is the first report of a child with evident meningeal enhancement on magnetic resonance imaging related to lumbar puncture.

Preliminary assessment of captopril sonography in screening for renal artery stenosis.

RATIONALE AND OBJECTIVES: We assessed the usefulness of the resistive index (RI) and renal length in predicting a significant renal artery stenosis (RAS) and evaluated the effect of captopril on the RI in kidneys with and without a significant RAS. METHODS: The RIs and renal lengths of both kidneys were measured in 39 patients who were referred for captopril renography for suspected renovascular hypertension. The difference in RIs (delta RI), the smaller RI (SRI), the difference in lengths (delta L), and the shorter length (SL) of the patient's two kidneys were determined. The accuracy of each of these parameters was calculated using captopril renography (n = 39) and arteriography (n = 9) as the gold standards. RESULTS: There was a significant difference in the delta RI (P < .05), SRI (p < .001), and delta L (p < .05) in patients with a positive captopril renogram for a significant RAS. Captopril increased delta RI (p = .052) in patients with a positive captopril renogram (n = 6). Use of an SRI threshold of less than .55 resulted in ultrasound being as accurate as captopril renography in predicting an angiographically documented stenosis of greater than or equal to 50%. CONCLUSION: The RI and renal length are useful in detecting a significant RAS. In this preliminary study, captopril was shown to increase delta RI in patients with a significant RAS, but larger prospective studies are necessary to further assess the value of captopril sonography in detecting a significant RAS.

Nonoperative treatment of double lateral ligament tears of the ankle.

In this article the objective evaluation of 39 cases of double lateral ligament tears of the ankle treated by cast immobilization is described. Such treatment resulted in a 79.5% success rate as determined by repeat stress roentgenograms. In addition, a statistical method which may aid the orthopaedist in deciding whether to use nonoperative or operative treatment is presented.

An examination of age and cognitive test performance across job complexity and occupational types.

In this study, job complexity and occupational type were examined as potential moderators of the relationship between age and cognitive ability. Data included general, verbal, and numerical ability scores for 21,646 individuals in the General Aptitude Test Battery (GATB) data base. These individuals comprised 102 unique samples and 10 major occupational groups. Differences in the relationship between age and cognitive ability test scores were observed across occupational types but not for different levels of job complexity. Findings were discussed in terms of a need for research that examines specific life and work experiences and how such experiences may influence an individual's cognitive abilities across the life span.

Prohibitive failure rate of the total articular replacement arthroplasty at five to ten years.

Five- to 10-year follow-up was obtained on a series of total articular replacement arthroplasties performed at a single university-affiliated teaching hospital. Eighty arthroplasties were performed on 64 patients. Twelve patients (accounting for 14 hip arthroplasties) died. Follow-up was obtained on 62 of the 66 remaining hips (94%). Thirty-five hips had been revised (56%), 32 for acetabular loosening and 3 for femoral loosening, 1 of which led to femoral stem fracture. The average time to revision was 72 months (22 to 132 months). The revision procedures were extensive in terms of operative time, blood loss, and necessity of acetabular bone grafting. Follow-up of the 27 that had not been revised averaged 84 months and revealed 1 hip excellent, 5 good, 1 fair, and 20 poor results. The overall clinical failure rate (revisions plus clinically poor results) was 89% (55/62 hips). These results are far inferior to conventional total hip replacement, and the extent of the revision procedures indicates that this is not a conservative alternative to conventional total hip replacement.

Perthes' disease and the search for genetic associations: collagen mutations, Gaucher's disease and thrombophilia.

The role of heritable thrombophilic risk factors in the pathogenesis of the Perthes' disease is controversial. The clinical and radiological findings of Perthes' disease may be indistinguishable from those of Gaucher's disease, and the most common Jewish N370S Gaucher mutation is threefold greater in patients with Perthes' disease. Familial osteonecrosis of the femoral head is associated with variant mutations of collagen type II (COL2A1 mutations). We therefore studied the potential role of genetic thrombophilia and the Gaucher and COL2A1 mutations in children with Perthes' disease. Genomic DNA of 119 children with radiologically-confirmed Perthes' disease diagnosed between 1986 and 2005 was analysed for the thrombophilic polymorphisms Factor V Leiden, 677T-MTHFR and FIIG20210A. The results were compared with those of a group of 276 children without Perthes' disease. DNA was also analysed for the Gaucher mutations N370S, G insertion (84GG), L444P, Intron 2 (IVS2+1G>A) and R496H. Enzymic assays confirmed the Gaucher disease status. Collagen (COL2A1) mutations of the 12q13 gene were also analysed. The prevalence of thrombophilic markers was similar among the 119 patients with Perthes' disease and the 276 control subjects. The prevalence of the Gaucher mutation was consistent with Israeli population carriership data and did not confirm an earlier-claimed association with Perthes' disease. All 199 patients were negative for the studied COL2A1 mutations. We found no genetic association between Perthes' disease and either Gaucher's disease or COL2A1 mutations or increased genetic thrombophilia among our patients compared with the control group. A systematic review of case-control studies suggested that there was a positive association between Perthes' disease and Factor V Leiden. The impact of this association upon the disease, although not consistent across the studies, remains unclear.