Misaligned spinal rods can induce high internal forces consistent with those observed to cause screw pullout and disc degeneration

BACKGROUND CONTEXTManual contouring of spinal rods is often required intraoperatively for proper alignment of the rods within the pedicle screw heads. Residual misalignments are frequently reduced by using dedicated reduction devices. The forces exerted by these devices, however, are uncontrolled and may lead to excessive reaction forces. As a consequence, screw pullout might be provoked and surrounding tissue may experience unfavorable biomechanical loads. The corresponding loads and induced tissue deformations are however not well identified. Additionally, whether the forced reduction alters the biomechanical behavior of the lumbar spine during physiological movements postoperatively, remains unexplored.PURPOSETo predict whether the reduction of misaligned posterior instrumentation might result in clinical complications directly after reduction and during a subsequent physiological flexion movement.STUDY DESIGNFinite element analysis.METHODSA patient-specific, total lumbar (L1–S1) spine finite element model was available from previous research. The model consists of poro-elastic intervertebral discs with Pfirrmann grade-dependent material parameters, with linear elastic bone tissue with stiffness values related to the local bone density, and with the seven major ligaments per spinal motion segment described as nonlinear materials. Titanium instrumentation was implemented in this model to simulate a L4, L5, and S1 posterolateral fusion. Next, coronal and sagittal misalignments of 6 mm each were introduced between the rod and the screw head at L4. These misalignments were computationally reduced and a physiological flexion movement of 15° was prescribed. Non-instrumented and well-aligned instrumented models were used as control groups.RESULTSPulling forces up to 1.0 kN were required to correct the induced misalignments of 6 mm. These forces affected the posture of the total lumbar spine, as motion segments were predicted to rotate up to 3 degrees and rotations propagated proximally to and even affect the L1–2 level. The facet contact pressures in the corrected misaligned models were asymmetrical suggesting non-physiological joint loading in the misaligned models. In addition, the discs and vertebrae experienced abnormally high forces as a result of the correction procedure. These effects were more pronounced after a 15° flexion movement following forced reduction.CONCLUSIONSThe results of this study indicate that the correction of misaligned posterior instrumentation can result in high forces at the screws consistent with those reported to cause screw pullout, and may cause high-tissue strains in adjacent and downstream spinal segments.CLINICAL SIGNIFICANCEProper alignment of spinal posterior instrumentation may reduce clinical complications secondary to unfavorable biomechanics.     

Biochemotherapy of advanced metastatic renal-cell carcinoma: results of the combination of interleukin-2, alpha-interferon, 5-fluorouracil,vinblastine, and 13-cis-retinoic acid

Summary We conducted a phase I/II clinical trial evaluating the sequential outpatient combination of S.C. recombinant human interleukin-2 (rIL-2; given at 10 MIU/m² b.i.d. on days 3–5 of weeks 1 and 4 and at 5 MIU/m² on days 1, 3, and 5 of weeks 2 and 3), s.c. recombinant human alpha-interferon (rIFN-; given at 6 MIU/m² on day 1 of weeks 1 and 4 and on days 1, 3, and 5 of weeks 2 and 3 and at 9 MIU/m² on days 1, 3, and 5 of weeks 5–8), i.v. bolus 5-fluorouracil (5-FU; given at 1,000 mg/m² once weekly during weeks 5–8), and i.v. bolus vinblastine (given at 6 mg/m² once weekly during weeks 5 and 8) in conjunction with p.o. 13-cis-retinoic acid (13-C-RA; given at 35 mg/m² daily during weeks 1–8). Therapy was always given in the outpatient setting. Grade 3 constitutional symptoms (malaise, chills, fevers, anorexia) were observed in 4%–8% of treatment cycles and required a 50% reduction in the doses of rIL-2 and rIFN-. None of the patients experienced major 5-FU-related toxicities such as severe diarrhea and/or stomatitis; up to 20% of patients developed vinblastine-associated peripheral polyneuropathy, which was reversible after the cessation of therapy. 13-cis-Retinoic acid produced no significant side effect; no toxic death occurred. Among 24 patients with progressive metastatic disease, there were 4 complete remissions (lung, lymph nodes) and 6 partial remissions (lung, pleura, liver, lymph nodes, and peritoneal carcinosis), for an overall objective response rate of 42% (95% confidence interval, 22%–63%). An additional 13 patients achieved disease stabilization (54%). The median time to response was 3–4 months (range, up to 6 months); all responses are continuous. In summary, although the potential synergy of biochemotherapy plus 13-cis-retinoic acid requires further preclinical investigation, the current outpatient combination regimen (rIL-2, rIFN-a, 5-FU, vinblastine, and 13-C-RA) proved to be both safe and highly effective in patients with advanced metastatic renal-cell carcinoma. A current multiinstitutional prospectively randomized trial is comparing biochemotherapy with and without concomitant 13-C-RA against rIFN- plus vinblastine.     

Fibroblast growth factor induces primitive streak formation in rabbit pre-implantation embryos in vitro

Culturing of rabbit pre-implantation embryos was performed in Ham's F10 medium supplemented with polyvinylpyrrolidone. Under these culture conditions, day 6 post coitum blastocysts increased their diameter within 24 h to 80% of that of day 7 blastocysts grown in vivo. Despite this substained growth, the embryonic disc remained undifferentiated with clear signs of degeneration after 24 h of culture. Basic fibroblast growth factor (bFGF) was able to overcome this developmental block. After 12 h of culture, day 6 blastocysts showed pear-shaped embryonic discs, and after 24 h, the primitive streak with Hensen's node was visible. The bFGF had no comparable effects on day 5 and day 7 blastocysts. The embryonic discs of day 5 blastocysts degenerated, even in the presence of bFGF, whereas day 7 blastocysts were able to form their primitive streak, also in the absence of bFGF. TGF ₁ did not promote embryonic development in vitro. The data indicate that the onset of mesoderm formation in the rabbit is controlled by a growth factor of the FGF-family.     

Who pays for new technology?

New medical technology presents an interesting dilemma. While it can offer improvements in patient care, it is often quite expensive. Thus, many health care payers may not be as willing to cover care involving new technologies.     

Cardiac arrest caused by air embolism in the course of a partial liver resection--a rare anaesthesiological complication (author's transl)

Cardiac arrest occurred during resection of a metastasis of the liver. In spite of having a PEEP of 5 cm H2O during IPPV this could not be avoided. Beginning immediately with reanimation a "Restitutio ad integrum" was seen as demonstrated by EEG and ECG.     

Microsurgical replantation of an incompletely amputated penis

The use of microvascular techniques in the replantation of one partially amputated penis is presented. The advantages of these techniques are discussed. A review of the literature is included; penis-replantation results prior to the introduction of microvascular techniques are compared to results achieved since the advent of these techniques. The superior results associated with microsurgical techniques are demonstrated, and it is concluded that microsurgical replantation is the procedure of choice in the repair of penis amputations.     

Left vagus nerve stimulation suppresses experimentally induced pain

OBJECTIVE: To test whether electric stimulation of the vagus nerve has an antinociceptive effect in humans. BACKGROUND: In a variety of animal studies, vagus nerve stimulation was shown to inhibit nociceptive behavior as well as electric responses of spinal nociceptive neurons. In humans, chronic left vagus nerve stimulation is used to treat pharmacologically refractory epilepsy. METHODS: The authors investigated experimental pain in 10 patients with seizures before and twice after implantation of a vagus nerve stimulator by using different controlled stimuli, including noxious heat, tonic pressure, and short impact. Pain was quantified on a visual analogue scale. Twelve nonepileptic age- and gender-matched individuals served as control subjects. RESULTS: Vagus nerve stimulation reduced increasing pain associated with trains of five consecutive stimuli at 1.5-second intervals ("wind-up"; p < 0.001). In a similar manner, pain on tonic pressure was reduced by vagus nerve stimulation (p < 0.03). Pain associated with single-impact stimuli as well as heat pain thresholds were unaltered under vagus nerve stimulation. Thus, vagus nerve stimulation led to pain relief predominantly in experimental procedures in which pain magnitude was amplified by central processing. The antinociceptive effect was independent of the acute on-off cycles of vagus nerve stimulation. CONCLUSIONS: Vagus nerve stimulation is effective in reducing pain in humans. In humans, the antinociceptive effect might rely on central inhibition rather than alterations of peripheral nociceptive mechanisms. These results indicate a promising, potential future role of vagus nerve stimulation in pain treatment.     

Endocrine effects of dehydroepiandrosterone and its fluorinated analog,fluasterone, in rats

Cancer chemoprevention is the use of pharmacologic agents to inhibit the development of cancer. The adrenal steroid dehydroepiandrosterone (DHEA) has demonstrated chemopreventive efficacy in animal models of tumorigenesis. However, due to DHEA's undesirable hormonal actions, the fluorinated analog fluasterone (fl‐DHEA), which also has chemopreventive characteristics, was synthesized as a potential alternate agent. It is not known whether fl‐DHEA has hormonal actions. The endocrinologic effects of DHEA and fl‐DHEA in adult male and female Fischer 344 rats were examined following 28 days of daily oral treatment. Initial doses tested were 30 and 300 mg/kg/day for each drug (n=12/sex/group), which are equivalent to 104 and 1,042 µmoles/kg/day DHEA, and 103 and 1,034 µmoles/kg/day fl‐DHEA. However, due to weight loss at the high dose, doses were lowered to 150 mg/kg/day for each drug (521 and 517 µmoles/kg/day DHEA and fl‐DHEA, respectively). Administration of DHEA resulted in dose‐dependent increases in plasma DHEA and DHEA‐S 1 h after dosing in week 4. DHEA produced an estrogenic effect in female rats expressed as decreased plasma FSH and LH, inhibition of ovulation, prolonged estrus, and increased uterine estrogen receptors. DHEA also increased plasma levels of androstenedione in males and females. Administration of fl‐DHEA increased the estrus cycle length due to a prolonged diestrus II phase and decreased the weights of the uterus, prostate, seminal vesicles, and testes. In addition, fl‐DHEA decreased plasma FSH, LH, and tissue estradiol, and increased plasma dihydrotestosterone levels in both sexes. These results indicate that fl‐DHEA is hormonally active and additional studies are warranted to further describe its endocrinologic effects. Drug Dev. Res. 58:169–178, 2003. © 2003 Wiley‐Liss, Inc.     

Interleukin-2- and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a Prospectively Randomized Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).

PURPOSE: We conducted a prospectively randomized clinical trial to compare the efficacy of three outpatient therapy regimens in 341 patients with progressive metastatic renal cell carcinoma. PATIENTS AND METHODS: Patients were stratified according to known clinical predictors and were subsequently randomly assigned. Treatment arms were: arm A (n = 132), subcutaneous interferon alfa-2a (sc-IFN-alpha-2a), subcutaneous interleukin-2 (sc-IL-2), and intravenous (IV) fluorouracil; arm B (n = 146): arm A treatment combined with per oral 13-cis-retinoic acid; and arm C (n = 63), sc-IFN-alpha-2a and IV vinblastine. RESULTS: Treatment (according to the standard 8-week Hannover Atzpodien regimen) arms A, B, and C yielded objective response rates of 31%, 26%, and 20%, respectively. Arm B, but not arm A, showed a significantly improved progression-free survival (PFS) compared with arm C (P =.0248). Both arm A (median overall survival, 25 months; P =.0440) and arm B (median overall survival, 27 months; P =.0227) led to significantly improved overall survival (OS) compared with arm C (median OS, 16 months). All three sc-IFN-alpha-2a-based therapies were moderately or well tolerated. CONCLUSION: Our results established the safety and improved long-term therapeutic efficacy of sc-IL-2 plus sc-INF-alpha-2a-based outpatient immunochemotherapies, compared with sc-INF-alpha-2a/IV vinblastine.