Closing patellar tendon defects after anterior cruciate ligament reconstruction: absence of any benefit

The most common graft in anterior cruciate ligament (ACL) surgery involves using the central one-third of the patellar tendon. Knowledge concerning the postoperative disability after harvesting the patellar tendon is, however, limited. The aim of this study was to evaluate the impact patellar tendon suture and bone grafting of the patellar bone defect might have in terms of functional outcome and patellofemoral pain after harvesting the bone-tendon-bone graft, compared with leaving the harvested site non-sutured and non-grafted. Sixty patients, scheduled for arthroscopically assisted ACL reconstruction, were randomly allocated to two groups. In group I, suture of the patellar tendon and bone grafting of the patellar defect were performed. In group II, the tendon gap and the patellar defect were left open. Preoperatively, there was no significant difference between the groups when comparing objective knee stability, as measured with a KT-1000 laxity meter, Lysholm score, Tegner activity level, IKDC score, or patellofemoral pain score. Both groups had a significantly improved Lysholm score at the 2-year follow-up, without any difference between them. Tegner's activity level was significantly lower at follow-up, compared with the pre-injury level in both groups. The patellofemoral pain score improved significantly after the reconstruction, without any difference between the groups. Ultrasonography did not reveal any difference between the groups in terms of healing of the tendon gap. This study revealed no differences in donor site morbidity, functional outcome, patellofemoral pain score or knee joint stability between the two treatment groups. The conclusion is that suture of the patellar tendon and bone grafting of the patellar defect do not improve the functional results or reduce donor site morbidity after arthroscopically assisted ACL. Received: 17 December 1996 Accepted: 30 July 1997     

Early events of hepatic metastasis formation in mice: role of Kupffer and NK-cells in natural and interferon-gamma-stimulated defense

Surgical manipulation of a tumor may result in increased influx of tumor cells into the systemic and portal circulation and give rise to formation of metastases. In addition, major surgery has been reported to cause profound immunosuppression. In an attempt to increase the host-antitumor immune mechanisms following surgery we have studied the effect of preoperative administration of interferon-gamma, related to the antimetastatic effects of Kupffer cells (KC) and natural killer cells (NK-cells) in the early phase of liver metastasis formation. Colon carcinoma cells were injected into the superior mesenteric vein of syngeneic mice and after 17 days metastases were quantified by weight, number, and uptake of [125I]iododeoxyuridine. Unstimulated control mice developed 10.5 surface nodules per liver 17 days following injection of colon carcinoma cells into the superior mesenteric vein of syngeneic mice. This figure was only 2.6 in mice stimulated with a single dose of 1000 IU IFN-gamma 4 h prior to inoculation of tumor cells. Administration of GdCl3, which is reported to deplete and block the function of Kupffer cells, 24 h prior to tumor cell inoculation resulted in a 5-fold tumor mass increase relative to control. Injection of anti-asiolo-GM1 antiserum, which eliminates the hepatic NK-cells, induced a 10-fold increase in tumor mass. These results indicate an important early antimetastatic function of hepatic NK-cells and KC and that presurgical administration of IFN-gamma may be important for eliminating circulating tumor cells and inhibiting development of residual tumors.     

Kinematics and laxity of the knee joint after anterior cruciate ligament reconstruction: pre- and postoperative radiostereometric studies

BACKGROUND: Injury of the anterior cruciate ligament changes the kinematics of the knee joint. In studies of cadaveric knees, investigators have examined the effect of anterior cruciate ligament reconstruction on knee kinematics, but the effect on dynamic knee motion is not known. HYPOTHESIS: Reconstruction of the anterior cruciate ligament restores knee kinematics to normal. STUDY DESIGN: Prospective cohort study. METHODS: Nine patients were examined preoperatively and 1 year after reconstruction. Continuous radiostereometric exposures were performed at a speed of two to four exposures per second while the patients ascended an 8-cm high platform. Tibial rotation and tibial and femoral translation were measured with radiostereometric analysis. RESULTS: Tibial rotation and tibial and femoral translation were not significantly different after anterior cruciate ligament reconstruction compared with preoperative measurements. A radiostereometric evaluation of anterior knee laxity revealed restoration to within 1 mm of that on the uninjured side. Further evaluation of knee function using the Lysholm score, the Tegner activity level score, the International Knee Documentation Committee evaluation system score, and measurements of laxity using the KT-1000 arthrometer revealed significant improvements after reconstruction. CONCLUSION: Kinematics of the anterior cruciate ligament injured knee did not change significantly after ligament reconstruction, but the functional results were satisfactory and knee laxity was diminished.     

Copper, ceruloplasmin, superoxide dismutase and iron parameters in Parkinson's disease

In a previous study we found copper dyshomeostasis in patients with Alzheimer's disease. In this study, levels of copper in plasma, of ceruloplasmin in serum and ceruloplasmin oxidative activity as well as superoxide dismutase (SOD) activity in erythrocytes were determined in 40 patients with Parkinson's disease and their healthy age- and gender-matched controls. Copper concentrations did not differ significantly in the two groups, whereas both ceruloplasmin concentrations and ceruloplasmin oxidative activity were significantly lower in the patients, also relative to ceruloplasmin mass. SOD activity was not significantly different in the two groups but decreased significantly with the duration of disease. The same was found for ceruloplasmin oxidative activity. Ceruloplasmin oxidative activity and SOD activity did not decrease with age. Levels of serum iron, serum ferritin and total iron binding capacity were determined in about 30 of the patients and an equal number of controls and were not found to differ. Transferrin levels were significantly lower in the patients than in their controls but, conversely, the transferrin saturation was significantly higher in the patients. The results indicate that patients with Alzheimer's disease and Parkinson's disease have defective ceruloplasmin and SOD activities in common and that these defects are not necessarily associated with major disturbances in iron homeostasis.     

Intranasal bioavailability of diazepam in sheep correlated to rabbit and man.

The purposes of the present study were to estimate the nasal bioavailability of diazepam in sheep and to compare this to earlier results in rabbits and humans. Additional, to compare the absorption during various initial periods in the two animal models and man, due to the importance of early absorption in emergency treatment. In a cross-over design, diazepam was nasally administered (7 mg) and intravenously (3 mg), respectively, to six sheep. Diazepam was solubilised in polyethylene glycol 300 in the nasal formulation. The mean nasal bioavailability, t(max) and C(max) were 15% (S.D.+/-8), 5 min (S.D.+/-3) and 934 ng/ml (S.D.+/-593), respectively. Sheep bioavailability was lower than rabbit 54% (P<0.001) and man 34% (P<0.05). In conclusion, the nasal absorption of diazepam was found to be fast, indicating the potential of nasal delivery in acute treatment. The initial (30 min) nasal bioavailability (30 min) for sheep and rabbit is a factor of 2.3 lower and 1.6 higher than man, respectively. The correlation of bioavailability was not optimal between sheep, man and rabbit with differences both in relation to extend and rate.     

Postoperative analgesic effects of an external cooling system and intra-articular bupivacaine/morphine after arthroscopic cruciate ligament surgery

The aim of this study was to evaluate the analgesic effect of an external cooling system with or without the combined effect of intra-articularly administered bupivacaine/morphine after arthroscopic anterior cruciate ligament (ACL) reconstruction. Fifty patients with isolated ACL insufficiency operated on under general anaesthesia were randomized to three different postoperative treatment groups. Group I was treated with the cooling system during the first 24 h after surgery and an intraarticular injection of 20 ml of physiological saline given at the completion of surgery; in group II, the cooling system was combined with an intra-articular injection of 20 ml bupivacaine 3.75 mg/ml and 1 mg of morphine at the end of the operation; while group III (placebo group) received an intra-articular injection of 20 ml of physiological saline at the completion of surgery. Pain was assessed using a visual analogue scale (VAS) at 1, 2, 4, 6, 24 and 48 h postoperatively. Supplementary analgesic requirements were registered. In group I 80% (16/20) and in group II 90% (18/20) of the patients were satisfied with the postoperative pain control regimen (NS). This was significantly better than in group III, where 30% (3/10) were satisfied. The pain scores were significantly lower in the two treatment groups compared with the placebo group during the entire postoperative period. The pain score was significantly lower in group II than in group I at 24 and 48 h after surgery. The supplementary analgesic requirements were also lower in the two treatment groups compared with the placebo group. No complications due to the use of the cooling system or the intra-articular injections of bupivacaine/morphine were observed. The external cooling system used in this study provides an effective method of obtaining pain relief after arthroscopic surgery. The combination with an intra-articular injection of morphine and bupivacaine results in a slightly greater analgesic effect than the cooling system alone.     

Sun exposure and sunburn among Swedish toddlers

Skin cancer is an emerging public health problem in Sweden. Even though the most important preventable risk factor for the development of skin cancer--sun exposure--is known, the incidence of skin cancer is still increasing. Studies have showed an association between increased risk of skin cancer and sunburn early in life. The aim of the present paper was to examine the frequency of sun exposure, sunburn and use of sun protective measures among an urban sample of Swedish toddlers. In March 2003, the parents of 4000 randomly selected children born between September 2001 and August 2002 were contacted by mail, and asked to fill out an enclosed questionnaire. The questionnaire concerned their own and their one-year-old child's sun exposure and sunburn history, and a few questions about knowledge, attitudes and protective activities were also included. One fifth of the children had been severely sunburnt at least once. Thirty-six percent of all children had been abroad on vacation to a sunny resort. More knowledge among parents increased the likelihood that the child was properly protected when in the sun, and parents own time in the sun was positively related to child's time in the sun. Being of the opinion that children look healthier when tanned was also positively associated with child sunburn. Thirty-five percent of all parents spent two hours or more in the sun during peak hours (11a.m. - 3p.m.) on a typical work-free day in the summer, and almost 10% of all parents had their children exposed to the sun for two hours or more during peak hours. We conclude that children in Sweden seem to get exposed to extensive sun exposure very early in life. Information and increased knowledge among parents to young children seems to be a potential way of increasing sun protection behaviour and decrease sun exposure among very young children.     

Risk of anastomotic leakage with use of NSAIDs after gastrointestinal surgery

Purpose  

Analgesic regimes to avoid opioid-related adverse effects have been recommended in gastrointestinal surgery. Non-steroidal anti-inflammatory drugs (NSAIDs) are an important component of opioid sparing regimes in that these drugs indirectly reduce pain by inhibiting inflammation. Although beneficial for most surgical patients, animal studies and recent clinical studies suggest a harmful effect on new intestinal anastomoses by increasing the rate of leakage. NSAIDs may indirectly disturb anastomotic healing by inhibiting inflammation as an integrated part of the wound healing process in an early, critical phase after surgery.     

Effects of small molecule inhibitors of PI3K/Akt/mTOR signaling on neuroblastoma growth in vitro and in vivo

Activation of the PI3K/Akt signaling pathway is correlated with poor prognosis in neuroblastoma, the most common and deadly extracranial tumor of childhood. In this study, we show that the small-molecule inhibitors of phosphoinositide-dependent protein kinase-1 (PDK1) OSU03012 and the dual class I PI3K/mTOR inhibitor PI103 have profound effects on neuroblastoma survival in vitro and in vivo. Both OSU03012 and PI103 inhibited neuroblastoma growth in vitro. In treated cells, OSU03012 induced apoptosis and an S phase cell cycle arrest, whereas only minor apoptosis was detected in PI103 treated cells together with a G1 arrest. Both OSU03012 and PI103 downregulated phosphorylation of Akt and inhibited the downstream targets glycogen synthase kinase-3β (GSK3β) and p70 S6 kinase-1 (S6K1), as well as downregulated the expression of cyclin D1 and Mycn protein. Neuroblastoma cells expressing high levels of Mycn were more sensitive to OSU03012 or PI103 compared with cells expressing low Mycn levels. Both compounds significantly inhibited the growth of established, subcutaneous MYCN-amplified neuroblastoma xenografts in nude NMRI nu/nu mice. These results suggest that inhibition of the PI3K/Akt signaling pathway represent a clinical relevant target for the treatment of patients with high-risk MYCN-amplified neuroblastoma.     

Serum osteoprotegerin in young survivors of myocardial infarction

Osteoprotegerin (OPG) is a member of the tumour necrosis factor superfamily and is involved in the regulation of bone metabolism and vascular calcification. Increased serum OPG levels have been reported in patients with stable angina pectoris and survivors of myocardial infarction with heart failure. The purpose of the present study was to determine serum OPG levels in young survivors of acute myocardial infarction (MI), and the relationship between OPG, homocysteine, sCD40L and coagulation factors in blood. Fifty-eight patients with verified MI, 40-60 years of age, were recruited 1-4 years after the acute event into an age- and sex- matched case control study with controls recruited from the general population. Serum OPG levels were similar in cases (2.41 ng/ml, 2.11-2.77 ng/ml) (mean, 95% CI) and controls (2.43 ng/ml, 2.11-2.79 ng/ml) (p = 0.92). Significant correlation between OPG and homocysteine was found in patients (r = 0.30, p = 0.02) and controls (r = 0.35, p = 0.007). A significant negative correlation was found between OPG and sCD40L in patients (r = -0.51, p < 0.001), but not in controls (r = 0.001, p = 0.96). No associations were found between serum OPG and markers of coagulation activation. The present study shows that serum OPG level was not increased in young survivors of uncomplicated myocardial infarction. Serum OPG levels were not associated with thrombin generation assessed by thrombin-antithrombin complexes (TAT), but a positive association between serum OPG and homocysteine was found.