Thermodynamic and kinetic basicities of the carbon and oxygen ends of enolates. Their role in the reductive cleavage electrochemistry of α-substituted acetophenones

The electrochemical reductive cleavage of α-substituted acetophenones may follow a mechanism in which electron transfer and bond breaking are concerted, as with α-chloro-acetophenone, or a mechanism where the two steps are successive, as with, e.g. α-benzoyloxy–acetophenone. In both cases, the resulting phenacyl radical is immediately reduced, giving rise to the phenacyl enolate, the protonation of which is expected eventually to yield acetophenone. However, in cyclic voltammetry, the acetophenone wave, present at low scan rates, vanishes upon raising the scan rate. The disappearance of the wave is observed at lower scan rates when an acid, such as phenol, is added to the solution. This surprising behavior is the result of the oxygen end of the enolate being a thermodynamically weaker but kinetically faster base than its carbon end.     

Rigid ureteroscopy: a reliable, non-aggressive technic. Apropos of 51 cases treated for ureteral lithiasis

The authors obtained 82% good results by using rigid ureteroscopy to treat a total of 55 calculi in a series of 51 patients and they propose the following therapeutic approach: calculi in the lumbar ureter are frequently difficult to reach (54% failures). There is no harm in gently trying to remove the stone by ureteroscopy which, in the event of failure, can be followed by percutaneous surgery or posterolumbar incision. Rigid ureteroscopy is easier and more reliable in the case of calculi in the iliac or pelvic ureter (7% failures) and the indications can be extended.     

Dose Responses for Neostigmine and Edrophonium as Antagonists of Mivacurium in Adults and Children

Background: Reversal of neuromuscular blockade induced with pancuronium, d-tubocurarine, or doxacurium is achieved using smaller doses of neostigmine in adults than in children. Also, pancuronium- and doxacurium-induced blockade is reversed with smaller doses of edrophonium in children than in adults. The purpose of this study was to compare the spontaneous and neostigmine- and edrophonium-assisted recovery of mivacurium-induced neuromuscular block in adults and children.

Methods: Fifty-four adults, aged 40.1+/-10.9 yr, and 54 children, aged 4.9+/-0.7 yr, physical status ASA 1-2, were studied during propofol/fentanyl/nitrous oxide anesthesia. A Datex relaxograph was used to monitor the electromyographic response of the adductor pollicis to train-of-four stimulation of the ulnar nerve every 10 s. After induction of anesthesia, 0.2 mg *symbol* kg sup -1 intravenous mivacurium was administered followed by an infusion to maintain 90-95% T1 block. At the end of surgery, one of four doses of neostigmine (5, 10, 20, and 50 micro gram *symbol* kg sup -1) or edrophonium (100, 200, 400, and 1,000 micro gram *symbol* kg sup -1) or placebo was given, by random allocation, when T1 had recovered to 10%. Values of T1 and train-of-four were measured for 10 min.

Results: Spontaneous recovery proceeded more rapidly in children than in adults. At 10 min, T1 had recovered to 97+/-2% (SD) in children compared with 69+/-11% in adults and train-of-four to 84 +/-5% versus 30+/-13% (P < 0.0001). In children, 10 min after reversal, recovery of T1 and train-of-four was not different from control after edrophonium and was enhanced only by the larger doses of neostigmine. In adults, recovery was accelerated by both edrophonium and neostigmine. Five minutes after reversal, recovery was improved by either drug in adults and in children.     

Early coagulopathy in trauma patients: an on-scene and hospital admission study

PurposeAmongst trauma patients, early coagulopathy is common on hospital admission. No studies have evaluated the initial coagulation status in the pre-hospital setting. We hypothesise that the coagulopathic process begins at the time of trauma. We studied the on-scene and on hospital arrival coagulation profile of trauma patients.MethodsProspective, observational study investigating the on-scene coagulation profile and its time course. We studied 45 patients at the scene of the accident, before fluid administration, and on hospital admission and classified their coagulopathy using the International Society on Thrombosis and Haemostasis score during a 2-month period. Prothrombin time, activated partial thromboplastin time, fibrinogen concentration, factors II, V and VII activity, fibrin degradation products, antithrombin and protein C activities, platelet counts and base deficit were measured.ResultsThe median injury severity score was 25 (13–35). On-scene, coagulation status was abnormal in 56% of patients. Protein C activities were decreased in the trauma-associated coagulopathy group (p = .02). Drops in protein C activities were associated with changes in activated partial thromboplastin time, prothrombin time, fibrinogen concentration, factor V and antithrombin activities. Only factor V levels decreased significantly with the severity of the trauma. On hospital admission, coagulation status was abnormal in 60% of patients. The on-scene coagulopathy was spontaneously normalised only in 2 patients whereas others had the same or a poorer coagulopathy status. All parameters of coagulation were significantly abnormal comparing to the on-scene phase. Decreases in protein C activities were related to the coagulation status (p < .0001) and changes in other coagulation parameters. Patients with base deficit ≤?6 mmol/L had changes in antithrombin, factor V and protein C activities but no significant coagulopathy.ConclusionCoagulopathy occurs very early after injury, before fluid administration, at the site of accident. Coagulation and fibrinolytic systems are activated early. The incidence of coagulopathy is high and its severity is related to the injury and not to hypoperfusion.     

Prolonged ingestion of commercial DDT and PCB; effects on progesterone levels and reproduction in the mature female rat

A report linking human polycystic ovary with increased exposure to environmental DDT (Heinrichset al. 1971) prompted the present study comparing effects of PCB and DDT or their combination on reproduction in female rats under more realistic conditions with respect to level (75 and 150 ppm), route of administration (dietary contaminant), and period of exposure (8 and 36 weeks). Evaluation of estrous cycle length, mating frequency, number and size of litters; as well as plasma levels of DDT, PCB, progesterone (P), and 17=hydroxyprogesterone (17=OH-P), permitted comparison of short and long term reproductive changes from ingestion of two levels of DDT and/or PCB.PCB reduced plasma progesterone (p<.01) while plasma 17 OH-P was unchanged by PCB or DDT. High DDT and PCB abolished reproduction. Histologically, distinct ovarian stromal changes accompanied 150 ppm of PCB, while increased numbers of more prominent follicular cysts were evident with 150 ppm of DDT. Although DDT and PCB generally reduced or abolished litter production, no treatment tested significantly altered litter size. Long term chronic ingestion of more realistic levels of technical DDT (85%p,p, 15%o,p-DDT) in these studies did not lead to polycystic ovaries in adult rats comparable to those reported following i.v. administration of pureo,p-DDT to immature rats. Plasma DDT levels above 800 ppb are clearly detrimental to reproduction, while levels below 500 ppb had little effect. Finally, we present the first evidence reported to our knowledge demonstrating that prolonged ingestion of PCB (150 ppm) markedly reduces reproduction (p<.05) accompanied by significantly reduced progesterone in plasma (p<.01) as well as by histologically characteristic ovarian stromal changes not seen with DDT alone.     

The replacement of graft endothelium by recipient-type cells conditions allograft rejection mediated by indirect pathway CD4(+) T cells

BACKGROUND: Whereas the participation of alloreactive T cells sensitized by indirect allorecognition in graft rejection is well documented, the nature of recipient antigen presenting cells recognized by indirect pathway CD4(+) T cells within the graft has yet to be identified. The purpose of this study was to determine the role played by graft endothelium replacement in the immune recognition of cardiac allografts rejected by indirect pathway CD4(+) T cells. METHODS: Transgenic RAG2(-/-) mice expressing I-A(b)-restricted male antigen H-Y-specific TcR were studied for their capacity to reject H-2(k) male cardiac allografts. Chronic vascular rejection in this model was due to the indirect recognition of H-Y antigen shed from H-2(k) male allograft and presented by the recipient's own I-A(b) APC to transgenic T cells. RESULTS: Immunohistochemical analysis of rejected grafts revealed the presence of numerous microvascular endothelial cells (EC) that expressed recipient's I-A MHC class II molecules. This observation suggested that graft endothelium replacement by I-A(b)-positive cells of recipient origin could stimulate the rejection of male H-2(k) graft by I-A(b)--restricted H-Y--specific T cells. To investigate further this possibility, hearts from H-2(b)--into--H-2(k) irradiation bone marrow (BM) chimera were transplanted in transgenic recipients. A direct correlation was observed between the presence of I-A(b)-positive EC within myocardial microvessels and the induction of acute rejection of chimeric H-2(k) male cardiac allografts transplanted in transgenic recipients. CONCLUSIONS: We conclude that graft endothelium replacement by recipient-type cells is required for the rejection of cardiac allograft mediated by indirect pathway alloreactive CD4(+) T cells.     

Surgery for right ventricle to pulmonary artery conduit obstruction: risk factors for further reoperation.

OBJECTIVE: To identify the surgical approaches and risk factors which influence longevity of right ventricle to pulmonary artery (RV-PA) conduits following first reoperation for obstruction. METHODS: Between January 1993 and August 2003, 114 patients underwent 141 reoperations for RV-PA conduit obstruction. Diagnoses included 'Truncus Arteriosus' (n=52), 'Pulmonary atresia/Tetralogy of fallot' (n=39), 'Double outlet right ventricle' (n=10), 'Transposition of great arteries, VSD, and pulmonary atresia' (n=9), and the 'Ross operation' (n=4). All patients had undergone a previous biventricular repair. The first reoperation for conduit obstruction was performed in 112 hospital survivors by: total conduit replacement (Group A, n=73) with valved (homograft=10 and xenograft=54) or non-valved (n=9) conduit, and patch enlargement of the obstructed RV outflow tract with preservation of the posterior and sides of the conduit wall after removing of the fibrocalcific peel and degenerated valve (Group B, n=39). Mean age at first reoperation was 8.8+/-6.7 and 7.5+/-5.3 years in patients of groups A and B, respectively. Seven patients in Group A and 18 in Group B required a second reoperation and two patients in Group B a third reoperation. RESULTS: There were two hospital deaths and no late deaths. Mean follow-up was 5.8+/-3.2 years. Risk factors for second reoperation by univariate analysis were: homograft conduit use (P=0.004), Group B surgical approach (P=0.0001), higher RV-PA systolic pressure gradient at discharge (P=0.02), and age <5-years-old (P=0.01). Multivariate analysis showed that inclusion in Group B and younger age (<5-years-old) at repair were independent risk factors for second reoperation. Group B surgical approaches had higher RV-PA systolic pressure gradient at discharge (P=0.02) and required more PA bifurcation repair at the time of second reoperation (P=0.05). Freedom from second reoperation for conduit obstruction was significantly higher in Group A patients at 5 and 8 years (P<0.04) and those with xenografts rather than homograft (P=0.04). CONCLUSIONS: Our results support the optimal surgical approach for RV-PA conduit obstruction is total replacement with a xenograft. RV outflow reconstruction by other techniques without complete dissection of PA bifurcation does not completely relieve the stenosis and could cause early restenosis. Higher systolic gradients at discharge and younger age at first reoperation are predictors of earlier reoperation.     

Classification of sporadic Creutzfeldt-Jakob disease based on clinical and neuropathological characteristics

Creutzfeldt-Jakob disease (CJD) is a rare and fatal neurodegenerative disease of unknown cause. Patients are usually aged between 50 and 75 and typical clinical features include rapidly progressive dementia associated with myoclonus and a characteristic electroencephalographic pattern. Neuropathological examination reveals cortical spongiform change, hence the term 'spongiform encephalopathy'. Several statistical techniques were applied to classify patients with sporadic CJD (sCJD), based on clinical and neuropathological investigation. We focus on the classification of neuropathologically confirmed sCJD patients. In order to obtain a classification rule that correctly classifies this type of patients and at the same time controls the overall error rate, we apply several classification techniques, which in general, produce comparable results. The boosting method produces the best results and the variable 14-3-3 protein in cerebrospinal fluid plays the most important role in the prediction of neuropathologically confirmed sCJD.