The role of elastoviscosity in the efficacy of viscosupplementation for osteoarthritis of the knee: a comparison of hylan G-F 20 and a lower-molecular-weight hyaluronan.

The objective of this 12-week, double-masked, randomized, multicenter study was to compare the elastoviscous properties of a high-molecular-weight viscosupplement, hylan G-F 20 (polymer concentration, 0.8%), with those of a lower-molecular-weight hyaluronan (LMW HA) product (polymer concentration, 1%) and to determine the relationship of elastoviscosity to efficacy in the treatment of patients with osteoarthritis (OA) of the knee. Patients had radiographically confirmed primary idiopathic OA of the knee (Larsen grades I to V) with pain despite other treatments. After a 2-week washout period, 70 patients (73 knees) received three 2-mL intra-articular injections of test solution at 1-week intervals. Thirty-eight patients (38 knees) received hylan G-F 20, and 32 patients (35 knees) received LMW HA. During the 12-week follow-up period, the primary outcome measures assessed by patients (using a visual analogue scale) were weight-bearing pain, most painful knee movement, and overall treatment response; the primary outcome measures assessed by study evaluators were weight-bearing pain and overall assessment of treatment. The dynamic elastoviscous properties of the test solutions were measured on an oscillating Couette-type rheometer. Hylan G-F 20 was more elastoviscous than the LMW HA at all frequencies measured (0.001 to 10 Hz). At the final evaluation, patients who received hylan G-F 20 had significantly better results on all primary outcome measures compared with those who received LMW HA. No systemic adverse events were reported. Local adverse events consisted of pain or swelling, noted in 2 of 38 knees injected with hylan G-F 20, and pain, noted in 1 of 35 knees injected with LMW HA (adverse event rates per injection, 1.8% and 0.9%, respectively). The difference in the incidence of adverse events between groups was not statistically significant. The higher-molecular-weight, more elastoviscous hylan G-F 20 had significantly greater pain-relieving effects than did the lower-molecular-weight, less elastoviscous hyaluronan.     

Shortening diclofenac therapy by B vitamins. Results of a randomized double-blind study, diclofenac 50 mg versus diclofenac 50 mg plus B vitamins, in painful spinal diseases with degenerative changes

The use of nonsteroidal anti-inflammatory drugs (NSAID) such as diclofenac for treatment of degenerative rheumatic disorders of the lumbar spine is of great significance in orthopedic practice. Clinical studies have shown that concomitant treatment with vitamins B1, B6, B12 and diclofenac provides more efficient pain relief than treatment using diclofenac alone. This study was undertaken in order to determine whether the duration of treatment with diclofenac for lower back pain can be shortened by adding B-vitamins to the therapeutic regimen. From September through December of 1986, 256 patients participated in a multicenter, controlled, randomized double-blind trial which compared the clinical efficacy of diclofenac (50 mg) with a combined therapy of diclofenac (50 mg) and vitamins B1, B6, and B12 (thiamine nitrate, pyridoxine hydrochloride, and cyanocobalamine, resp.; in dosages of 50 mg, 50 mg, and 0.25 mg, resp.). Patients were treated with 3 X 1 capsule daily for a maximum of two weeks, having the option to terminate participation in the trial after 1 week in the event of total pain relief. The data of 238 patients were able to be included in the evaluation. 29 patients opted to discontinue therapy due to remission on symptoms. Nineteen (65.6%) of these patients belonged to the combined therapy group, the other 10 (34.4%) having taken diclofenac alone; this difference is statistically significant (p less than 0.05). An important aspect in the evaluation of therapy was the patient response regarding the improvement of painful symptoms which, in addition to their subjective feedback, was reflected in the test results of the "Hoppe Pain Questionnaire (HPQ)." All parameters used as a measure of pain relief indicated superior results with the B-vitamin supplemented therapy when compared with results obtained with diclofenac alone. Moreover, after 3 days of therapy the "sensory" pain factor "sharpness" improved significantly. Undesirable side-effects were documented with 39 patients, 14 of them having discontinued therapy for this reason. No statistically significant difference could be determined within this group with regard to therapy. The study results document the positive influence of B-vitamins on painful symptoms and indicate that less NSAID is needed for pain relief when combined with B-vitamins.     

Human pharmacokinetics and safety evaluation of SonoVue, a new contrast agent for ultrasound imaging

RATIONALE AND OBJECTIVES: To assess in humans the pharmacokinetics of SonoVue, a new echo contrast agent based on stabilized sulfur hexafluoride (SF6) microbubbles and to provide additional safety and tolerability information on the compound. METHODS: The blood kinetics and pulmonary elimination of SF6 after intravenous bolus injection of two dosage levels (0.03 and 0.3 mL/kg) of SonoVue were evaluated in 12 healthy subjects (7 men, 5 women). In addition, safety and tolerability were evaluated by monitoring vital signs, adverse effects, discomfort, and physical examination and laboratory parameters associated with the SonoVue injection. RESULTS: The blood kinetics of SF6 was not dose dependent. SF6 was rapidly removed from the blood by the pulmonary route, with 40% to 50% of the injected dose eliminated within the first minute after administration and 80% to 90% eliminated by 11 minutes after administration; the elimination was similar in men and women and independent of dose. Both dosages were well tolerated. No adverse effects were observed immediately or during the 24-hour follow-up period. CONCLUSIONS: SonoVue was shown to be rapidly removed from the blood. The route of SF6 elimination was by means of the lungs in the expired air. SonoVue appeared to be safe and well tolerated in healthy subjects.     

Oncogenic transformation increases the sensitivity for apoptosis induction by inhibitors of macromolecular synthesis

Inhibition of RNA or protein synthesis causes apoptosis in fibroblasts. This points to the constitutive expression of a long-lived apoptosis machinery which is controlled by shortlived negative regulatory proteins, termed endogenous survival factors. The length of time between addition of the inhibitor of macromolecular synthesis and the onset of apoptosis can be used as an estimation of the effective survival factor concentration. Transformation of rat fibroblasts by a constitutively expressed src oncogene or an inducible ras oncogene increases the sensitivity for apoptosis induction by inhibitors of macromolecular synthesis, indicating that their endogenous survival factor pool has been decreased.     

Effect of surface topography on removal of cortical bone screws in a novel sheep model

Difficulty in removing implants used in trauma patients can be a complication, and increased bone–implant adhesion likely is a major contributing factor. In vitro studies have shown that surface morphology of implant materials has the ability to influence cellular responses, with polished surfaces decreasing the potential for mineralization. This study examined the effect of polishing commercially pure titanium (cpTi) and the titanium alloy TAN on the removal torque and percentage bone–implant contact in cortical and cancellous bone of sheep. Polishing had a significant effect on both removal torque and percentage bone–implant contact, with the polished implants demonstrating a lower removal torque in both cortical and cancellous bone. Polished cpTi and stainless steel were similar in terms of surface roughness and removal torque. However, polished TAN, which was not as smooth as polished cpTi, did not show the same low level for reducing removal torque. Improved polishing of TAN should reduce the removal torque further. The results of the study show that polishing is promising in improving the ease of implant removal after fracture fixation and repair. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1377–1383, 2008     

Laparoscopic robotic-assisted gastrointestinal surgery: the Geneva experience

The continuing development of robotic surgery supports its use in laparoscopic gastrointestinal surgery. Our study retrospectively reviewed the surgical outcome and patient’s satisfaction of gastrointestinal laparoscopic robotic procedures. From January 2003 to September 2007, 94 patients (27 women, 67 men) with a mean age of 53 years (range 19–84 years) underwent laparoscopic surgery with a da Vinci robotic system. There were 40 colorectal cases (43%), 31 anti-reflux surgery cases (33%) and 14 obesity surgery cases (15%); the remaining cases consisted of gastric and gallbladder surgery, intra-abdominal tumour excisions, and hepatic cyst resections. The majority of the cases (88, 94%) were performed for benign disease. The mean operative time was 153 min (range 60–330 min). One patient needed a blood transfusion. The mean body mass index was 25 (range 16–47). No death occurred. Five cases (5.3%) were converted to conventional laparoscopic surgery (n = 3) or to laparotomy (n = 2). Morbidity consisted of one Nissen redo surgery to loosen a tight anti-reflux valve 6 days after robotic surgery, a robotic left ureter repair and pelvic haemorrhage following proctectomy requiring re-operation to control haemostasis and to remove pelvic haematoma. Mean follow-up time was 11 months (range 15 days to 34 months). One case of incisional trocar hernia needed re-operation. Overall patient’s satisfaction was high: few scars were cheloïd, while functional surgical outcome was rated high by most of the patients. Our preliminary experience was encouraging, with minimal morbidity and very high acceptance by patients.     

AML1-ETO inhibits maturation of multiple lymphohematopoietic lineages and induces myeloblast transformation in synergy with ICSBP deficiency

The translocation (8;21), generating the AML1-ETO fusion protein, is one of the most frequent chromosomal abnormalities associated with acute myelogenous leukemia (AML). To elucidate its role in oncogenesis, bone marrow (BM) cells were infected with a retroviral vector carrying AML1-ETO and transplanted into mice. In contrast to previous transgenic mouse models, we show that AML1-ETO directly stimulates granulopoiesis, suppresses erythropoiesis, and impairs the maturation of myeloid, B, and T lymphoid cells in vivo. To determine the significance of earlier findings that expression of the tumor suppressor ICSBP is often downregulated in AML myeloblasts, AML1-ETO was introduced into BM cells derived from mice lacking the interferon regulatory factor ICSBP. Our findings demonstrate that AML1-ETO synergizes with an ICSBP deficiency to induce myeloblastic transformation in the BM, reminiscent of AML.     

Delayed onset of partial epilepsy of temporal lobe origin following acute clioquinol encephalopathy.

Twelve cases have been reported in the literature to have developed acute, largely reversible, global amnesic syndromes some hours after ingesting substantial doses of clioquinol. Two of these cases presented again after asymptomatic intervals of some 12 years. Both had recently developed typical clinical and electroencephalographic evidence of partial epilepsy originating in a temporal lobe. The similarity of clinical events in these two subjects, the absence of any other known cause for their epilepsy and the fact that, in mice, acute clioquinol overdosage causes hippocampal and amygdaloid injury, suggest that the drug was responsible for both the acute encephalopathy and the epilepsy of delayed onset.     

Absence of benefit of incentive spirometry in low-risk patients undergoing elective cholecystectomy. A controlled randomized study

To determine the potential benefit of incentive spirometry, which has been advocated to prevent pulmonary complications after upper-abdominal surgery, we compared a group of patients receiving incentive spirometry to another group receiving no specialized postoperative respiratory care. Forty patients in the American Society of Anesthesiologists' class 1 and 2 who were undergoing cholecystectomy (through right subcostal incision) were included in the study and were randomly allocated to one of the two groups. Patients receiving incentive spirometry were encouraged by a specialized respiratory physiotherapist to breathe deeply for five minutes hourly, 12 times daily, for three postoperative days. No statistically significant difference between the two groups was found in the radiologic evidence of postoperative pulmonary complications, arterial oxygen pressure, spirometric measurement, and clinical evaluation at the second or fourth postoperative day (or both). In particular, deterioration on the chest x-ray film at the fourth postoperative day was observed in eight of 20 patients in the group receiving incentive spirometry and in six of 20 in the control group. Our study confirms the postoperative deterioration of respiratory function after upper-abdominal surgery and demonstrates the lack of therapeutic values of incentive spirometry in these patients at low risk for pulmonary complications.