Modified cervical laminoforaminotomy based on anatomic landmarks reduces need for bony removal.

We describe a modified keyhole laminoforaminotomy (LF) using anatomic landmarks on the posterior aspect of the cervical vertebral body to decompress the intervertebral foramen with minimal bone removal. Twenty-four procedures were performed at C3-4, C4-5, and C5-6; 12 at C6-7; and 3 at C7-Tl. Facets and laminae structures were identified based on relative surgical perspectives. Bony resection was limited as follows: 1) inferior limit; inferior border of the superior facet; 2) superior limit, superior border of the superior facet; 3) lateral limit, a vertical line linking the junction of the lamina-facet to the lateral end of the superior limit; and 4) lateral aspect of the dural sac. Fluoroscopy was used to confirm that the intervertebral space was reached. The amount of bony removal was quantified for the superior and inferior laminae and facets. The length of the exposed nerve root was measured. The intervertebral foramen was exposed and the intervertebral disc reached in all specimens. Fluoroscopy showed that the center of the exposure remained at the same height with the intervertebral space. The mean length of the nerve root was 4.6 mm; the mean percentage of bony resection was 21.8%, 7.5%, 11.3%, and 11.5% for the superior and inferior laminae and facets, respectively. Opening the intervertebral foramen posteriorly consistently exposed sufficient nerve root length and allowed access to the intervertebral disc. The technique offers the most direct and safest method of decompressing the intervertebral foramen while minimizing bony resection. This simple surgical procedure may help reduce postoperative morbidity.     

Differential effects of within-day continuous vs. transient dopamine D2 receptor occupancy in the development of vacuous chewing movements (VCMs) in rats.

Accumulating evidence suggests that antipsychotics (APs) that lead to sustained blockade of dopamine D(2) receptors are more likely to induce acute extrapyramidal side effects (EPS) compared to APs that only occupy D(2) receptors transiently. It is unclear, however, whether a similar relationship exists for long-term AP-induced motoric side effects like tardive dyskinesia (TD). The objective of this study was to ascertain whether transient (via daily subcutaneous (s.c.) injections) vs continuous (via osmotic minipump) AP-induced D(2) receptor occupancy differentially affects the development of haloperidol-induced vacuous chewing movements (VCMs), an animal model of TD. Six groups of 12 rats received 0.1, 0.25, or 1 mg/kg of haloperidol or vehicle (n=36) via osmotic minipump (to provide within-day sustained) or daily s.c. injection (within-day transient) for 8 weeks. VCMs were measured on a weekly basis and D(2) occupancy levels were measured in vivo using [(3)H]-raclopride at the end of the experiment. Minipump-treated rats developed HAL dose-dependent D(2) occupancies of 0.1 mg/kg/day (57%), 0.25 mg/kg/day (70%), and 1 mg/kg/day (88%). S.C.-treated rats also developed HAL dose-dependent D(2) occupancies of 0.1 mg/kg/day (83% peak, 3% trough), 0.25 mg/kg/day (89% peak, 0% trough), and 1 mg/kg/day (94% peak, 17% trough). A total of 43% of rats given 0.25 and 1 mg/kg/day of HAL via minipump developed high VCMs compared to only 8% of the rats given the same doses via daily s.c. injections. The 0.1 mg/kg dose did not give rise to VCMs beyond vehicle levels regardless of the route of administration. These findings support the contention that D(2) occupancy levels induced by chronic HAL must be high and sustained through the day before significant risk of VCMs, and perhaps also TD, emerges.     

Priming with a very low dose of DNA complexed with cationic block copolymers followed by protein boost elicits broad and long-lasting antigen-specific humoral and cellular responses in mice

Cationic block copolymers spontaneously assemble via electrostatic interactions with DNA molecules in aqueous solution giving rise to micellar structures that protect the DNA from enzymatic degradation both in vitro and in vivo. In addition, we have previously shown that they are safe, not immunogenic and greatly increased antigen-specific CTL responses following six intramuscular inoculations of a very low dose (1 μg) of the vaccine DNA as compared to naked DNA. Nevertheless, they failed to elicit detectable humoral responses against the antigen. To gain further insight in the potential application of this technology, here we show that a shorter immunization protocol based on two DNA intramuscular inoculations of 1 μg of DNA delivered by these copolymers and a protein boost elicits in mice broad (both humoral and cellular) and long-lasting responses and increases the antigen-specific Th1-type T cell responses and CTLs as compared to priming with naked DNA. These results indicate that cationic block copolymers represent a promising adjuvant and delivery technology for DNA vaccination strategies aimed at combating intracellular pathogens.     

Factors affecting aseptic loosening of 4750 total hip arthroplasties: multivariate survival analysis

Background  

Total hip arthroplasty is a successful surgery, that fails at a rate of approximately 10% at ten years from surgery. Causes for failure are mainly aseptic loosening of one or both components partially due to wear of articular surfaces and partially to design. The present analysis aimed to identify risk factors and quantify their effects on aseptic failure.     

Treatment of intervention sites of malignant pleural mesothelioma with radiotherapy: a Dutch-Belgian survey.

A survey was performed on the radiotherapy practice of malignant pleural mesothelioma in The Netherlands and Belgium in 2002. Thirty-eight out of 47 centres (81%) responded. Prophylactic radiotherapy to intervention sites is given by 32/38 (84%) centres, with all centres offering palliative radiation. For both prophylactic and palliative indications, all centres use hypo-fractionated schedules. The present study shows that in the radiotherapy community in The Netherlands and in Belgium, a de facto consensus exists that both prophylactic and symptomatic radiotherapy to intervention sites of malignant pleural mesothelioma are effective and that hypo-fractionated schedules should be used.     

Assessing ethical problem solving by reasoning rather than decision making

Context The assessment of ethical problem solving in medicine has been controversial and challenging. The purposes of this study were: (i) to create a new instrument to measure doctors’ decisions on and reasoning approach towards resolving ethical problems; (ii) to evaluate the scores generated by the new instrument for their reliability and validity, and (iii) to compare doctors’ ethical reasoning abilities between countries and among medical students, residents and experts. Methods This study used 15 clinical vignettes and the think‐aloud method to identify the processes and components involved in ethical problem solving. Subjects included volunteer ethics experts, postgraduate Year 2 residents and pre‐clerkship medical students. The interview data were coded using the instruments of the decision score and Ethical Reasoning Inventory (ERI). The ERI assessed the quality of ethical reasoning for a particular case (Part I) and for an individual globally across all the vignettes (Part II). Results There were 17 Canadian and 32 Taiwanese subjects. Based on the Canadian standard, the decision scores between Taiwanese and Canadian subjects differed significantly, but made no discrimination among the three levels of expertise. Scores on the ERI Parts I and II, which reflect doctors’ reasoning quality, differed between countries and among different levels of expertise in Taiwan, providing evidence of construct validity. In addition, experts had a greater organised knowledge structure and considered more relevant variables in the process of arriving at ethical decisions than did residents or students. The reliability of ERI scores was 0.70–0.99 on Part I and 0.75–0.80 on Part II. Conclusions Expertise in solving ethical problems could not be differentiated by the decisions made, but could be differentiated according to the reasoning used to make those decisions. The difference between Taiwanese and Canadian experts suggests that cultural considerations come into play in the decisions that are made in the course of providing humane care to patients.     

TGF-β and IL-17 serum levels and specific immunotherapy

Two new T cell subsets may be involved in allergic rhinitis (AR) pathogenesis: Th17 and T regulatory cells, mainly producing IL-17 and TGF-β respectively. Successful Sublingual Immunotherapy (SLIT) induces relevant immunological changes, thus the aim of this study was to evaluate serum IL-17 and TGF-β levels in AR patients treated with SLIT for 2 years. Patients' blood samples were collected before initiating SLIT (baseline), three months after the end of the first pre-seasonal SLIT course, and at the end of the second pre-seasonal course. IL-17 was detectable only in the most severe allergic patients. SLIT significantly induced an increase in serum TGF-β levels. There was moreover a significant relationship between TGF-β and symptom severity and drug use at the end of the study. Therefore, this study provides clinically relevant evidence that two pre-seasonal SLIT courses may significantly affect serum TGF-β levels.