Effect of L-carnitine on oxidative stress and platelet activation after major surgery.

BACKGROUND: The surgical/anesthesia trauma is associated with an increased production of reactive oxygen species (ROS). This enhanced oxidative stress leads to cell damage resulting in various complications such as sepsis, myocardial injury and increased mortality. The aim of this study was to investigate the role of antioxidant treatment with l-carnitine in oxidative stress and platelet activation in patients undergoing major abdominal surgery. METHODS: Forty patients scheduled for abdominal surgery were randomly allocated to l-carnitine, administered with a rapid infusion (0.05 g/kg) diluted in 250 ml of saline solution, vs. placebo treatment just before the surgical intervention. At baseline and after treatment, oxidative stress was evaluated by detection of circulating levels of soluble NOX2-derived peptide (sNOX2-dp), a marker of NADPH oxidase activation, and by analyzing platelet ROS formation. Platelet activation was studied by dosing sCD40L. RESULTS: We observed an increase of soluble sNOX2-dp, sCD40L and ROS production in the placebo group compared with the baseline after the surgical intervention. Conversely, in the l-carnitine-treated group, sNOX2-dp, sCD40L and ROS production did not significantly differ from the baseline. A linear correlation analysis showed that Δ of ROS correlated with Δ of sNOX2 (R(s) =0.817; P<0.001) and Δ of sCD40L (R(s) =0.780; P<0.001). Multiple linear regression analysis showed that the only independent predictive variable associated with Δ of ROS was Δ of serum NOX2 levels (SE=0.05; standardized coefficient ß=1.075; P<0.001). CONCLUSION: Our findings suggest that l-carnitine could be helpful in modulating oxidative stress and platelet activation during major abdominal surgery-dependent oxidative damage.

Chemoradiation for anal squamous cell carcinoma: case report.

INTRODUCTION: Anal squamous cell carcinoma is rare and seems to be associated with chronic inflammatory conditions, infections and immunosuppression. Their incidence has been arising since the last 25 years. Compared to adenocarcinoma of the rectum and squamous cell cancer of the anal canal, squamous cell carcinoma is a distinct entity with a different etiology, pathogenesis, prognosis and requires a different therapeutic approach. Even if surgery remains the main therapeutic option, recent advances have made chemoradiation a valuable therapeutic addition. This case discuss the efficacy of chemoradiation wich can prevent complications and can improve the quality of life. CASE REPORT: A 63-year-old woman presented with history of bloody stool for the last past month. The colonoscopy showed a 2 cm circular lesion on the posterior wall of the anal canal. Biopsy was positive for squamous cell carcinoma and afterwards the patient underwent chemoradiation. At 1 year of follow-up the patient is disease free, with a good sphincter control and had no late complications. CONCLUSION: Since the first studies in 1974, chemoradiation seems to be a good option for most patients with squamous cell carcinoma avoiding surgery.

[Constraint-induced movement therapy in the rehabilitation of hemineglect after a stroke]. / Terapia del movimiento inducido por restricción en la rehabilitación de la heminegligencia después de un ictus.

INTRODUCTION: Hemineglect produces a lower capacity for recovery after the stroke and so far there are no rehabilitation techniques that have proven to be effective at functional level. AIMS: The main objective of this work was to assess whether the modified constraint-induced movement therapy (mCIMT)for hemineglect produces greater benefits than conventional therapy on functional hemineglect. Secondary objectives were to assess whether mCIMT produces greater benefits on upper and lower limb function as well as on the degree of autonomy and disability of patients with in relation to conventional therapy. PATIENTS AND METHODS: We have recruited 30 patients with ischemic stroke and diagnosis of hemineglect randomly assigned to mCIMT group (n = 15) or conventional therapy group (n = 15). We used the Catherine Bergego Scale (CBS) for assessment hemineglect; Fugl-Meyer tests for the motor function of lower and upper limb, and Barthel index and modified Rankin scale for the rest of objectives. RESULTS: We have found significant differences in favour of mCIMT group in the CBS after treatment and three months later once finished. We have not found differences between groups for the rest of variables. CONCLUSIONS: mCIMT could be a more effective therapy than conventional therapy to improve the symptoms of hemineglect in the acute stroke. However, it may be clinically more recommended in patients with a certain motor function after stroke.

TITLE: Terapia del movimiento inducido por restricción en la rehabilitación de la heminegligencia después de un ictus.Introducción. La heminegligencia produce una menor capacidad de recuperación después del ictus y hasta el momento no existen técnicas de rehabilitación que hayan demostrado ser funcionalmente efectivas. Objetivos. El objetivo principal de este trabajo fue valorar si la terapia de movimiento inducido por restricción modificada (TMIRm) para la heminegligencia produce mayores beneficios que la terapia convencional sobre la heminegligencia funcional. Los objetivos secundarios fueron evaluar si la TMIRm produce mayores beneficios en la función del miembro superior y del miembro inferior, así como sobre el grado de autonomía y discapacidad de los pacientes con respecto a la terapia convencional. Pacientes y métodos. Se seleccionó a 30 pacientes con ictus isquémico y diagnóstico de heminegligencia, que fueron asignados aleatoriamente al grupo de TMIRm (n = 15) o al grupo de terapia convencional (n = 15). Se empleó la Catherine Bergego Scale (CBS) para la valoración de la heminegligencia; las pruebas Fugl-Meyer para la función motora del miembro inferior y del miembro superior, y el índice de Barthel y la escala de Rankin modificada para el resto de los objetivos. Resultados. Se hallaron diferencias significativas en favor del grupo de TMIRm para la CBS en la valoración después del tratamiento y a los tres meses de finalizado. No se encontraron diferencias entre grupos para el resto de las variables. Conclusiones. La TMIRm podría ser una terapia más efectiva que la convencional para mejorar la sintomatología de la heminegligencia en la fase aguda del ictus. Sin embargo, podría ser clínicamente más recomendable en pacientes con una determinada función motora después del ictus.

Perioperative management in patients undergoing pancreatic surgery: the anesthesiologist's point of view.

BACKGROUND: A high rate of mortality and morbidity has been associated with pancreaticoduodenectomy; the 5-year survival rate is 15% to 25% compared with 1% to 5% among those who did not have any cancer-directed treatment. Systemic rather than surgical complications cause the majority of perioperative deaths, so the anesthesiologist has a crucial role in the management of these patients. This work sought to evaluate an improved approach to perioperative pain management, postsurgical complications as well as outcomes. PATIENTS: From 2002 to 2007, 40 patients underwent pancreaticoduodenectomy for pancreatic or periampullary cancer. The anesthesia protocol was standardized for postoperative pain control. Patients were randomly divided into two groups: 16 patients received an epidural analgesia with local anesthetics combined with opioids (T(9)-T(10); group A) and 24 had IV analgesia with morphine (group B). RESULTS: Postoperative mortality was 2.5%. With regard to complications we observed 4 biliary fistulas, 2 pancreatic fistulas with spontaneous healing in one patient and death in the other as well as wound infections. Patients treated with epidural analgesia experienced better pain relief, compared with subjects receiving IV analgesia, which demonstrated a higher incidence of opioid-related adverse effects such as sedation and respiratory depression. CONCLUSION: Adequate perioperative treatment included suitable nutritional support and pain management using loco-regional techniques, which seem to improve the surgical outcomes among pancreatic cancer patients.

Mitochondrial perturbations and oxidant stress in lymphocytes from patients undergoing surgery and general anesthesia.

BACKGROUND: Previous studies have shown that a profound suppression of immune function transiently occurs in patients who undergo surgery under general anesthesia. The decline in the absolute counts of peripheral blood lymphocytes constitutes a major factor accounting for this immune defect, and recent evidence indicates that apoptosis plays a crucial role in determining postsurgical lymphocytopenia. HYPOTHESIS: An altered oxidation-reduction status of mitochondria may contribute through apoptosis to the loss of lymphocytes following surgical trauma and general anesthesia. DESIGN: We studied 16 patients with American Society of Anesthesiologists' physical status I or II who underwent elective surgery under general anesthesia. The data were collected prospectively. SETTING: University hospital. MAIN OUTCOME MEASURES: Samples of peripheral blood were drawn on the day before surgery and at 24 and 96 hours after the operation. Following lymphocyte isolation, the mitochondrial transmembrane potential was assessed by flow cytometry using 3,3'-dihexylocarbo-cyanine iodide, and stains with hydroethidine and 2'-7'-dichlorofluorescein diacetate were used to determine the generation of reactive oxygen species. The labeling of lymphocytes with monobromobimane was used to assess the presence of reduced glutathione. RESULTS: At 24 hours after surgery, we detected a significantly elevated frequency of peripheral blood lymphocytes (P =.002), which incorporated low levels of 3,3'-dihexylocarbo-cyanine iodide, compared with the preoperative period. At this same time point, the frequency of lymphocytes with the hydroethidine- and 2'-7'-dichlorofluorescein diacetate-positive phenotype was elevated compared with baseline levels. Conversely, at 24 hours after surgery, the frequency of cells that stained positive for glutathione was strongly decreased compared with preoperative values. Overall measurements returned to the baseline levels at 96 hours after surgery. CONCLUSION: The strict association we observed between the overproduction of reactive oxygen species and the disruption of the mitochondrial transmembrane potential supports the view that alterations in mitochondrial energy metabolism, paralleled by the presence of a pro-oxidant oxidation-reduction status, could be involved in the accelerated apoptotic loss of lymphocytes following surgical trauma and general anesthesia.

Heat shock protein (HSP70) expression in septic patients.

PURPOSE: This study investigates heat shock protein 70 (HSP70) expression by peripheral blood mononuclear cells (PBMCs) of septic patients admitted to an intensive care unit and examines the possibility of a correlation between HSP70 levels and plasma tumor necrosis factor alpha (TNF-alpha) concentrations. Additionally, we evaluated whether the HSP70 production could be regarded as a prognostic factor for the development of septic shock as well as for patient survival. MATERIALS AND METHODS: Blood samples of 29 patients were taken 24 hours after the diagnosis of sepsis. HSP70 expression and TNF-alpha level were measured using indirect immunofluorescent analysis and a commercially available enzyme-linked immunosorbent assay method, respectively. RESULTS: PBMCs expressed significantly high levels of HSP70 (11.9 +/- 5.6 [sd]) compared with those of the healthy control group (3.2 +/- 2.1% positive cells). Such enhanced levels were correlated to plasma TNF-alpha concentrations (r = .99, P < .01). This study failed to demonstrate a relationship between HSP70 production and clinical outcome. CONCLUSION: These findings give further evidence that also in humans, heat shock response is activated during sepsis. The correlation observed between HSP70 overproduction and TNF-alpha plasma concentrations suggests that HSP70 exerts a possible protective effect against TNF-alpha cytotoxicity. Such hypothesis has not been confirmed by our clinical data.

Plasmids as epidemiologic markers in nosocomial gram-negative bacilli: experience in an intensive care unit.

The authors have compared the antimicrobial resistance patterns and plasmid profiles of Gram-negative isolates in an intensive care unit over a 7-month period in order to identify epidemiologically related isolates. Bacterial plasmids were found to be valuable markers for the comparison of strains of nosocomial Gram-negative bacilli. Thirty-nine mechanically ventilated patients in an ICU were included. From bronchoaspiratus, the authors isolated 58 strains of Gram-negative bacilli (24 Ps. aeruginosa and 34 Enterobacteria). Common plasmids were found in most Enterobacteria. The interspecies plasmid exchange suggests that interstate spread of these strains may have occurred. Twenty-six Enterobacteria carried plasmids, 11 of which proved transmissible. The R-factors were transferred to other genera that were isolated in the hospital, thereby adding to the pool of multiresistant nosocomial isolates. Larger plasmids transferred ampicillin and carbenicillin resistance, while gentamycin and cephalotin resistance was carried by smaller plasmids. Only 4 Ps. aeruginosa carried plasmids, one of which was transmissible. Pseudomonas plasmid DNA is extracted with difficulty by the simple lysis method, due to the roughness of the colonies. All Pseudomonas isolates belonged to the same biotype which can be regarded as an epidemiological marker. Therefore, plasmid profiling is a useful tool for epidemiological surveillance of Enterobacteria and is a good method for determining the relatedness of isolates in a nosocomial environment.

[Laparoscopic cholecystectomy: evaluation of intraoperative complications with respect to 2 different kinds of anesthesia]. / Colecistectomia laparoscopica: stima di alcune complicanze perioperatorie in rapporto a due differenti metodiche di anestesia.

Two anaesthetic managements for elective laparoscopic cholecystectomy were compared in 64 patients in order to investigate some perioperative complications: 1) bowel distension during surgery. 2) recovery from anaesthesia. 3) post-surgery incidence of emesis and pain. In addition, the quality of postoperative peristalsis as well as the time of dimissal were recorded. Group I (n = 30) was treated with NLA in N2O-O2 and Group II (n = 34) received propofol plus fentanyl in air-O2. Bowel distension, evaluated by surgeon at 15 min intervals throughout the operation was similar in both the groups as well as postoperative peristalsis recuperation. During the first 12 hours after laparoscopy no differences were found at any times of observation in the incidence or severity of emesis and pain between the two different anaesthesia patients. In subjects which were given propofol the psychomotor recovery was more rapid than after NLA, particularly during the first 6 hours after surgery. The patients were discharged between 36-48 hours following the operation independently from anaesthetic management. It is concluded that both the anaesthetic techniques provide similar intra/postoperative conditions, except the early recovery that is more rapid for the propofol patients. The overall frequency of emesis and pain was rather high in both the groups, suggesting a routine medication with analgesics and antiemetics.

[Treatment of trigeminal neuralgia with electroacupuncture. Experience with 104 cases]. / Il trattamento della nevralgia trigeminale con elettroagopuntura. Esperienza su 104 casi.

The essential or secondary trigeminal neuralgia is a very frequent and invalidant disease. In this forms, the medical or surgical conventional therapies are often inadequate. In this study we evaluated the effects of the acupunctural therapy on 104 patients (mean age 52.3 +/- 13 years) with idiopathic or secondary trigeminal neuralgia. Utilizing cycles of twelve sessions, the acupunctural treatment was performed with an electrostimulator on local points and a distance or on aching points, in the secondary forms. The results was evaluated on the basis of three parameters (reappearance of the symptomatology, absence of pain in months and preceding treatments) and was defined using this scale: very well, well, fair and null. In conclusion we can say that acupuncture is an elective treatment in all kinds of secondary tregeminal neuralgia, while, in the idiopathic form, its validity is conditioned by preceding medical treatments and by beginning of the disease.

["Killing" of pseudomonas aeruginosa isolated from patients with critical post-operative complications. Effect of various antibiotics]. / "Killing" di pseudomonas aeruginosa isolati da pazienti con complicazioni critiche post-operatorie. Influenza di alcuni antibiotici.

We undertook this study to estimate phagocytic killing by neutrophils (PMNs) of Pseudomonas aeruginosa pre-exposed to sub-inhibitory concentration of Amikacin and Imipenem. In particular, we have isolated bacteria from endotracheal aspirates of post-operative patients mechanically ventilated admitted to an ICU with respiratory failure. PMNs were obtained both from these patients (Group A, n. 6) as well as from subjects submitted to surgery with uncomplicated post-operative period (Group B, n. 8). From specimens tested, 6 strains of Pseudomonas aeruginosa were isolated. Results showed that the rate of killing of bacteria treated with Amikacin was no different from that of untreated bacteria, whichever the source of PMNs, either from Group A or Group B patients. On the other hand, the microbicidal effect on P. aeruginosa exposed to Imipenem was significantly enhanced when PMNs were obtained from Group B patients. In the mixture bacteria, Imipenem and PMNs obtained from Group A the rate of killing was low, similar to the controls without antibiotics. Such a finding suggests a possible impairment of PMNs due to the critical disease and in some way responsible for the host adverse interaction between granulocytes, antibiotics and pathogens. The underlying mechanisms remain to be clarified and further studies are required to understand the possible clinical implications.

[Thoracoscopic bilateral sympathectomy in Raynaud's syndrome. Anesthesiology problems]. / Simpaticectomia bilaterale per via toracoscopica nella sindrome di Raynaud. Problemi anestesiologici.

The objective of this paper was to examine the major anaesthetic problems during transthoracic endoscopic sympathectomy without artificial pneumothorax and to present our experience of 16 cases suffering from Raynaud's disease. For the perioperative management we used a double lumen endo-bronchial tube and balanced anaesthesia (intravenous agents plus isoflurane). Arterial pressure, heart rate, ECG, end-tidal carbon dioxide concentration, SatO2, blood gases and peak inspiratory pressures were monitored. The results showed that no significant changes in these parameters occurred during surgery. Since hypoxaemia is the main problem of the thoracoscopic sympathectomy the A.A. emphasize the necessity to ensure a correct ventilation as well as a haemodynamic stability throughout the procedure. The combination of balanced anaesthesia and double lumen endobronchial intubation seems an advisable method when no artificial pnx is instituted. A close monitoring of the circulatory and respiratory systems is imperative.

Lymphocyte apoptosis, caspase activation and inflammatory response in septic shock.

BACKGROUND: We examined lymphocyte apoptosis, activity of caspases-1, -3, -8 and -9 and the relationship between those two events and inflammation response in septic shock. MATERIALS AND METHODS: Blood samples were obtained within 24 h after diagnosis of septic shock from 16 patients to measure apoptosis, caspases-3, -8, -9 expression, changes in mitochondrial transmembrane potential and expression of Fas/FasL system of peripheral blood mononuclear cells (PBMCs). Moreover, serum levels of caspase-1 and blood concentrations of IL-6, IL-12, IL-15 and IL-18 were assessed. RESULTS: PBMCs from patients with septic shock compared to control individuals exhibited a greatly increased frequency of apoptosis (39.10 +/- 7.33% vs 4.19 +/- 1.13%; p < 0.001), an over expression of caspases-3, -8, and -9 (p < 0.01, p < 0.05, p < 0.001 for caspases-3, -8 and -9, respectively) as well as of Fas/FasL system (p < 0.05) and significant changes in mitochondrial transmembrane potential. Blood levels of caspase-1 (101.5 +/- 18.2 pg/ml vs 9.09 +/- 2.7 pg/ml, p < 0.001) and of IL-6, IL-12, IL-15 and IL-18 were significantly higher in septic patients vs control (p < 0.0001, p < 0.05, p < 0.05 and p < 0.0001, respectively). Furthermore, a correlation linking IL-6 blood level with both the apoptotic rate (r(2) = 0.75; p = 0.001) and caspase-9 expression (r(2) = 0.92; p = 0.0001) of PBMCs was observed.

Subarachnoid sufentanil as sole agent vs standard spinal bupivacaine in transurethral resection of the bladder.

AIM: The aim of the study was to determine whether intrathecal sufentanil alone provides an adequate analgesia for patients undergoing transurethral resection of the bladder (TURB) and to compare it to standard spinal bupivacaine anesthesia in terms of motor and sensory blockade, discharge time and side effects. METHODS: Sixty-two patients were blindly and randomly assigned to receive either intrathecal bupivacaine (10 mg of 0.5% hyperbaric bupivacaine) or intrathecal sufentanil (15 microg). Motor and sensory blockade was evaluated using a modified Bromage scale as well as cold and pinprick tests. Severity of pain was assessed by means of a 10-point verbal analog scale. RESULTS: We found that the mean duration of sensory blockade was similar for both sufentanil and bupivacaine patients but the quality of analgesia induced by sufentanil alone was poor as compared with spinal bupivacaine anesthesia. CONCLUSION: The subarachnoid administration of sufentanil 15 mg seems to be inadequate for TURB surgery. In addition, the advantage of a faster recovery we observed in sufentanil patients is minimized by the occurrence of a troublesome symptom such as pruritus. On the other hand, spinal bupivacaine produces an undesirable motor blockade exceeding, in our opinion, the requirement for TURB procedure.

Plasma levels of IL-10 and nitric oxide under two different anaesthesia regimens.

BACKGROUND AND OBJECTIVE: An alteration in production of both interleukin-10 (IL-10) and nitric oxide (NO) has been found following surgical/anaesthesia trauma. It is also suggested that IL-10 could be an important factor in regulating NO metabolism during the postoperative period. Furthermore, NO seems to play a crucial role in the anaesthetic state. The purpose of this study was to investigate plasma levels of IL-10 and NO following surgery, any possible correlation between these two variables and whether anaesthesia technique could influence NO and IL-10 circulating concentrations. METHODS: Thirty-two patients scheduled to undergo elective major surgery were enrolled in the study and allocated into two groups to receive two different techniques of anaesthesia, total intravenous (i.v.) anaesthesia (Group I) and inhalational anaesthesia (Group II). Blood samples were drawn before (t0), at the end (t1) of operation and after 24 h (t2). Plasma IL-10 and NO levels were measured by using an enzyme-linked-immunosorbent assay (ELISA) and a total NO assay kit, respectively. RESULTS: In both patient groups there was a significant decrease of plasma NO levels at the end of surgery (30.35 +/- 2.70 mmol L(-1) at t0 to 13.76 +/- 1.51 mmol L(-1) at t1 in Group I, P < 0.0001; 28.23 +/- 2.50 mmol L(-1) at t0 to 11.38 +/- 0.95 mmol L(-1) at t1 in Group II, P < 0.0001). This reduction remained at 24 h postoperatively (14.33 +/- 1.52 mmol L(-1) in Group I, P < 0.0001; 12.52 +/- 1.11 mmol L(-1) in Group II, P < 0.0001, both vs. t0). There was an increase in IL-10 concentrations (26.35 +/- 3.42 pg mL(-1) and 75.39 +/- 8.33 pg mL(-1) at t1 and t2, respectively, vs. 4.93 +/- 0.31 pg mL(-1) at t0, P = 0.03 and P < 0.0001, respectively, in Group I; 26.18 +/- 3.22 pg mL(-1) and 69.91 +/- 7.33 pg mL(-1) at t1 and t2, respectively, vs. 5.50 +/- 0.33 pg mL(-1) at t0, P = 0.02 and P < 0.0001, respectively, in Group II). No relationship was found between circulating IL-10 and NO. CONCLUSIONS: During the postoperative period, IL-10 overproduction does not correlate with the decrease in systemic NO concentration.

Arthroscopic Herbert screw fixation of patellar osteochondritis dissecans.

Osteochondritis dissecans of the patella is a rare cause of anterior knee pain. The lesion is thought to arise from chronic shear stress across the patella articular surface, producing a fragment of cartilage and subchondral bone that may remain in situ or become detached. When attempts at conservative treatment fail to provide satisfactory results, operative intervention is indicated. We present the case of a symptomatic lesion of the patella treated successfully with arthroscopic internal fixation using a retrogradely directed Herbert screw. The literature is reviewed with an emphasis on pathophysiology, diagnosis, and surgical treatment.

Pancuronium bromide, a non-depolarizing muscle relaxant which promotes apoptosis of blood lymphocytes in vitro.

BACKGROUND: Several compounds used in anesthesia practice have demonstrated to impair immune function and to influence the process of apoptotic death in T cell population following surgical trauma. We designed this study to test in vitro the impact of neuromuscular blocker, such as pancuronium, at clinically relevant concentration on lymphocyte apoptosis, death factor expression and mitochondrial function. METHODS: Following isolation, lymphocytes were incubated with pancuronium bromide at a clinically relevant concentration (0.136 micro mol l-1) for 3 h at 37 C in a 5% carbon-dioxide-humidified atmosphere and the frequency of apoptotic lymphocytes was then measured. We also investigated crucial steps in the apoptotic process, including Fas/Fas ligand (FasL) phenotype, intracellular expression of the interleukin-1beta-converting enzyme (ICE) p20, mitochondrial membrane potential (DeltaPsim), generation of mitochondrial reactive oxygen species, and glutathione (GSH) levels. Control experiments were performed incubating cells in the complete culture medium added with the dilution medium of the drug without addition of the drug. RESULTS: Expression of Fas, FasL and ICEp20 was six-fold, four-fold, and five-fold increased, respectively, among pancuronium-treated lymphocytes with respect to control cultures (P = 0.0001). The percentage of cells exhibiting either dissipation of mitochondrial membrane potential or increased production of reactive oxygen species was seven-fold increased following exposure to pancuronium compared with untreated lymphocytes (P = 0.0001). These findings were associated with a decrease in GSH level. In addition, the frequency of apoptotic cells was 10-fold greater among lymphocytes cultured in the presence of the drug with respect to control cultures. (P = 0.0001). CONCLUSION: Our data suggest an apoptogenic effect of pancuronium in vitro at clinically relevant concentration on peripheral blood lymphocytes. This could be implicated in the transient immune suppression following a surgical operation.

A conservative approach to anterior knee pain.

Eight-five patients with sole anterior knee pain were treated with a physical therapy program and a nonsteroidal antiinflammatory medication. Physical therapy consisted of regimented stretching exercises, quadriceps electrical stimulation, isometric quadriceps sets, ice application after treatment, progressive straight-leg raising, and short-arc quadriceps sets. After a disciplined progression of physical therapy and daily activity, patients were questioned about the amount of their knee dysfunction secondary to pain and their level of activity. Eighty-seven percent of these patients described their knee symptoms as improved immediately after a physical therapy program. Sixty-eight percent believed their symptoms were improved when reviewed at follow-up interview (mean duration, 16.0 months). All follow-up information was obtained via phone interview using a checksheet question form to eliminate subject bias. At the time of interview, 57% believed that their level of activity substantially increased from their level at initial evaluation. These data dictate that a trial of physical therapy and nonsteroidal antiinflammatory medication should be used as initial treatment for anterior knee pain.

[Proapoptotic effect of propofol on T cells]. / Effetto proapoptotico del propofol sulle cellule T.

BACKGROUND: Surgery and general anesthesia induce excessive apoptosis on peripheral lymphocytes and this phenomenon significantly contributes to the postoperative lymphocytopenia. However, the role played by anesthetic agents on this event remains to be elucidated. In this study we examined whether an anesthetic compound such as propofol is able to exert, in vitro, a proapoptotic effect on T cells. METHODS: Lymphocytes were isolated from heparinized venous blood in healthy volunteers and were incubated with propofol at clinically relevant concentration (5 mg/ml) and at 10 times this concentration (50 mg/ml). The counts of cells either bearing the Fas/FasL phenotype or expressing the intracellular Bcl2 protein were determined by means of flow cytometry. Assessment of lymphocytes undergoing apoptosis was made both by staining of apoptotic nuclei with propidium iodide (PI) and by phenotypic analysis of apoptotic cells with 7-amino-actinomycin D (7-AAD). RESULTS: Treated lymphocytes exhibit a significantly enhanced expression of Fas/FssL system associated with a decrease of Bcl2 expression at both 5 and 50 mg/ml propofol concentrations (p<0.05). On the other hand, the rate of apoptotic cells was not significantly different as compared to control in the absence of propofol. CONCLUSIONS: Propofol impairs, in vitro, both Fas/FasL and Bcl2 expressions on lymphocytes at clinically relevant concentrations but fails to induce apoptotic cell death. It is suggested that the antioxidative properties of the drug could inhibit some way the mechanisms by which mitochondrial free-radicals mediating apoptosis ultimately lead to cell death execution.

Interleukin-10 and apoptotic death of circulating lymphocytes in surgical/anesthesia trauma.

OBJECTIVE: To examine the relationship between circulating interleukin-10 (IL-10) and the occurrence of lymphocyte apoptosis after surgical/anesthesia trauma. METHODS: Data were collected prospectively on 18 adult patients undergoing elective major surgery. Blood sampling for assessment of lymphocyte apoptosis and IL-10 levels was performed on the day before surgery (t(0)) and at 24 and 96 hours after operation (t(1) and t(2), respectively). After lymphocyte isolation, quantification of apoptosis was made by staining apoptotic cells with 7-amino-actinomycin D. Plasma IL-10 concentrations were measured using enzyme-linked immunosorbent assay. RESULTS: A significantly increased frequency of apoptotic CD4(+) and CD8(+) cells (p < 0.05) was observed at t1 measurement (8.10% +/- 0.58% and 12.21% +/- 1.47% for CD4(+) and CD8(+), respectively) compared with preoperative values (1.53% +/- 0.38% and 1.32% +/- 0.45% for CD4(+) and CD8(+), respectively). Plasma IL-10 levels showed a significant elevation at both t(1) and t(2) times, peaking at t(1). At t(1), IL-10 levels were correlated with the frequency of CD4(+) and CD8(+) apoptotic lymphocytes (r = 0.78, p = 0.0005 for IL-10 vs. apoptotic CD4(+); r = 0.71, p = 0.003 for IL-10 vs. apoptotic CD8(+)). CONCLUSION: Surgical trauma is associated with a significant but transient increase in lymphocyte commitment to apoptosis and IL-10 production. The exact relationship linking the overproduction of IL-10 with lymphocyte apoptosis after a surgical operation is still elusive and requires further investigation.