Phospholipase A2 enzymes regulate alpha IIb beta3-mediated, but not Fc gammaRII receptor-mediated, pp125FAK phosphorylation in platelets

The alphaII(b)beta3 integrin and FcgammaRII receptors mediate, respectively, platelet adhesion and spreading on fibrinogen and immunoglobulin (IgG) coated surfaces. Platelet adhesion to fibrinogen resulted in a partial conversion of the faster to the slower migrating (phosphorylated) form of Ca(+2)-sensitive cytosolic phospholipase A2(cPLA2) but failed to trigger arachidonic acid (AA) release. Full mobility shift of cPLA2 and a massive release of AA release were stimulated by platelet adhesion to IgG or addition of thrombin to the fibrinogen adherent platelets. IgG and thrombin induced AA production were blocked by methyl arachidonyl fluorophosphonate (MAFP), an irreversible inhibitor of cPLA2 and the Ca(+2)-independent phospholipase A2 (iPLA2). In contrast, bromoenol lactone (BEL), a specific inhibitor of iPLA2 had no effect on the release of AA. MAFP and BEL prevented pp125FAK phosphorylation and platelet spreading on fibrinogen having no effect on pp125FAK phosphorylation or platelet spreading on immobilized IgG. We conclude that alpha(IIb)beta3-mediated pp125FAK phosphorylation and platelet spreading on fibrinogen are regulated by PLA2 enzymes.     

Surgical-site complications associated with a morphine nerve paste used for postoperative pain control after laminectomy.

OBJECTIVE: To identify risk factors that might explain a sudden increase in the rate of surgical-site complications following laminectomy. DESIGN: Retrospective cohort study. PATIENTS AND SETTING: Patients who underwent laminectomy at a 120-bed hospital from August 1 through October 15, 1996 (the epidemic period). A case-patient was defined as a patient with postoperative surgical-site complications (surgical-site drainage, edema, or swelling) requiring surgical debridement. RESULTS: Of the 148 patients who underwent a laminectomy during the epidemic period, 17 (11%) met our case definition. The rate of postoperative surgical debridement was 7.6-fold higher during the epidemic period than the preceding 19-month period (17/148 vs 15/995, P<.001). Development of surgical-site complications was associated with intraoperative receipt of morphine nerve paste (relative risk [RR], 11; P<.001), preoperative shaving by nurses rather than surgeons (RR, 6.6; P=.006), procedures done by a certain surgeon (RR, 3.1; P=.022), or receipt of iodine rather than povidone-iodine for preoperative skin antisepsis (RR, 5.1; P=.002). In multivariate analysis, only receipt of morphine nerve paste remained as a risk factor (RR, 18; P=.011). The paste was used to control postoperative pain and was applied directly to exposed dura and surrounding tissues. At the time of surgical debridement (median, 24 days postsurgery), the original surgical sites showed residual paste and a lack of healing. Ten of 16 cultures from surgical sites were positive; all but three grew skin commensals. Histological examination of surgical specimens showed a foreign-body reaction, but no marked acute inflammation. CONCLUSIONS: The intraoperative use of morphine nerve paste may delay wound healing and increase postoperative morbidity. When new products are introduced, standardized protocols should be developed for their use, and systematic surveillance should be done to monitor for potential adverse outcomes.     

Effects of photodynamic therapy using verteporfin on experimental choroidal neovascularization and normal retina and choroid up to 7 weeks after treatment.

PURPOSE: To study the long-term effects of photodynamic therapy (PDT), using liposomal benzoporphyrin derivative (BPD) or Verteporfin, on experimental choroidal neovascularization (CNV) and on normal retina and choroid (with no CNV) in the cynomolgus monkey eye. METHODS: Photodynamic therapy was performed in 8 cynomolgus monkey eyes with experimental CNV induced by laser injury. The effect of PDT on normal retina and choroid (with no CNV) was studied in 9 monkey eyes. Liposomal BPD was administered intravenously (0.375 mg/kg) either as a bolus, as a slow infusion over 32 minutes, or as a fast infusion over 10 minutes. Photodynamic therapy was performed using light at a wavelength of 689 or 692 nm, with an irradiance of 600 mW/cm2 and fluence of 150 J/cm2. Follow-up studies, including fundus photography and FA, were performed at 24 hours after PDT and then weekly. Indocyanine green and BPD angiography were performed in selected cases. Tissues were examined with light and electron microscopy at the end of follow-up. RESULTS: Twenty-three of the 32 areas of CNV treated with PDT showed absence of angiographic leakage at 24 hours. Twenty-eight areas of CNV were followed for 4 weeks; 22 of 28 showed absence of angiographic leakage at 2 weeks; and 20 of 28 at 4 weeks of follow-up. Forty spots on the normal retina and choroid were treated with PDT and were followed for 4 to 7 weeks. These spots showed pigment-laden cells in the outer retina, variably pigmented retinal pigment epithelium (RPE) in the treated area, intact neurosensory retina, and reperfusion of the choriocapillaris. CONCLUSIONS: Photodynamic therapy leads to absence of angiographic leakage for at least 4 weeks in experimental CNV in the monkey model. In the normal monkey eye the RPE and choriocapillaris show generalized recovery with preservation of the neurosensory retina 7 weeks after PDT.     

Physicians who keep lax records put careers in danger, college course warns.

During a recent workshop sponsored by the College of Physicians and Surgeons of Ontario, Dr. Paul Caulford identified the most common problems with medical records: they are much too brief, don't tell the patient's story and are missing important details. He warned that physicians must pay more attention to their records because "the way things are moving, the scrutiny of records in the past in nothing in comparison to what it will be like in the future."     

Actigraphically recorded motor activity and immobility across sleep cycles and stages in healthy male subjects

The aim of this study was to compare the extent to which activity and immobility measures are related to sleep stages and sleep cycles in order to improve the informative value of actigraphic assessment of sleep. We therefore performed simultaneous ambulatory polysomnography and wrist-activity monitoring (AM) in 14 healthy male subjects without sleep complaints. In this context, a simple method for transforming raw motor activity data into a time-series reflecting onset and duration of activity and immobility clusters is introduced. Our results demonstrate that nocturnal AM measures were significantly affected by sleep stage. Low activity levels and particularly prolonged episodes of uninterrupted immobility were associated with increasing sleep depth. On the other hand, high activity levels and prolonged episodes of activity were related to intermittent wakefulness during sleep. Our results suggest that measures reflecting the occurrence and duration of activity and immobility clusters provide a better approach in studying the relationship between activity/immobility and sleep stages. Except for the duration of uninterrupted immobility episodes, which showed a significant decrease in the fourth cycle, none of the AM measures showed a significant cycle-to-cycle variation. Consequently, mean nocturnal motor activity measures provide an accurate reflection of the total sleep period. However, none of the AM-derived measures seems useful in evaluating the cycle structure during sleep.     

306. Martin Kirschner zum 100. Geburtstag

Zusammenfassung Kirschner wurde 1879 in Breslau geboren. 1916 erhielt er den Ruf auf den Lehrstuhl in Königsberg, 1927 nach TÜbingen und 1934 nach Heidelberg. An diesen Stätten erbaute er neue Kliniken. Erfolgreich arbeitete er auf allen chirurgischen Teilgebieten. Besonders erwähnenswert seien die erste erfolgreiche pulmonale Embolektomie, die einzeitige Lungenlappenresektion, ein neues Verfahren in der Oesophaguschirurgie, die EinfÜhrung des halbstarren Kirschner-Drahtes, in der Schmerzbekämpfung die Avertinnarkose, die Spinalanaesthesie und die Elektrocoagulation des Ganglion Gasseri. 1932 begrÜndete er die heute von Zenker fortgefÜhrte Operationslehre.     

Phase II clinical trial of 4′-O-Tetrahydropyranyl-Adriamycin (THP-Adriamycin) in recurrent squamous cell carcinoma of the head and neck

Summary Fourteen patients previously treated with surgery, radiotherapy, and/or chemotherapy for primary squamous cell carcinoma of the head and neck were treated with 4-O-tetrahydropyranyl-Adriamycin (THP-adriamycin) for locally or distantly recurrent disease. The starting dose was 60 mg/m² by i.v. infusion, with courses repeated every 3 to 4 weeks. A total of 34 courses of treatment were delivered (median, 2; range, 1–6). All patients were evaluable for response and toxicity. There were no responses. Severe (grade 3 or 4) neutropenia occurred in 11 patients. Thrombocytopenia, anemia, and gastrointestinal toxicity were modest, and no hepatic, renal, or cardiac toxicity was observed. The lack of response in association with severe neutropenia and moderate other toxicities using this dose and schedule of THP-Adriamycin should be taken into consideration prior to the pursuit of further study of this compound in a similar patient population.     

A comparison of the effects of electrode placement, muscle tension, and isometric torque of the knee extensors

Numerous electrical stimulation (ES) papers have been published using a variety of electrode placements and muscle tension criteria levels, making cross-comparisons difficult. The purpose of this study was to compare isometric knee extensor torques produced using three methods to induce muscle tension and three electrode placements. Twenty-three healthy, informed female volunteers (mean age = 24 yrs, SD = 3.2 yrs) participated in a practice session and three test sessions, each approximately 48 hrs apart. One of three electrode placements was randomly assigned during each test session. Maximal voluntary isometric contractions (MVIC) preceded the electrically induced isometric torque outputs. Comfortably tolerable and maximally tolerable ES intensities were combined with each of the following electrode placements: 1) lumbosacral plexus/femoral triangle (LS), 2) femoral triangle/transverse distal quadriceps (F), and 3) transverse proximal/distal quadriceps muscle (Q). A two-way ANOVA with repeated measures, Neuman-Keuls, and tests of simple main effects were used to analyze the data. Significantly greater torques were produced during the MVlCs than during either type of electrically induced isometric torque output (p < 0.05). During ES, the maximally tolerable intensity level produced significantly greater torques than the comfortably tolerable intensity level (p < 0.05). The F and Q electrode placements produced similar torques, both significantly greater than the torque produced with the LS electrode placement (p < 0.05). The method to induce muscle tension (voluntary or electrically induced), the criteria defining the level of muscle tension (MVIC, maximally or comfortably tolerable ES), and the electrode placement (LS, F, or Q) affect knee extensor torques and should be considered when using ES and when interpreting ES studies. Although the ideal rehabilitation program typically includes voluntary exercise to provide overload, certain pathologies may contradict this choice. In its place, ES has the potential to minimize strength losses or create gains while offering joint protection. J Orthop Sports Phys Ther 1992;15(4):168-174.     

Marked increase of plasma hyaluronan after major thermal injury and infusion therapy

Hyaluronan (HYA) is an important structural element in skin and is presumably participating in regulation of the interstitial fluid volume. HYA is transported via the lymphatics from the tissues to the blood, where its concentration is normally very low. Fluid flux through the interstitium is markedly increased after thermal injury. The present study was performed to determine whether major thermal injury would affect plasma levels of HYA. In halothane-anesthetized sheep subjected to 40% BSA full-thickness scald burns, plasma HYA concentration increased from 116 +/- 19 (mean +/- SEM) to 172 +/- 18 ng/ml within 1 hr after injury (P less than 0.05). After 3 hr of fluid therapy plasma HYA concentration was further elevated to 10 times baseline (1417 +/- 322 ng/ml) (P less than 0.01). To clarify whether this rise represented an increased "washout" of interstitial HYA, attributable either to the burn injury or the subsequent fluid therapy, awake sheep were subjected to overhydration. Following a 3-hr infusion of lactated Ringer's 2.5 liter/hr, plasma HYA concentration increased to 2-3 times baseline. Lung lymph flow and its concentration of HYA increased, leading to an increase in the lymphatic flux of HYA to 10-20 times baseline. In peripheral lymph HYA flux increased 2-3 times baseline. Infusion of lactated Ringer's markedly increased lymphatic removal of HYA. However, plasma concentrations of HYA were 3 times higher after thermal injury than following fluid challenge alone, suggesting that thermal injury per se may also increase input of HYA into the systemic circulation.