Synthesis of 3'-alkylthio-2',3'-dideoxy nucleosides with potential anti-HIV activity from 2-deoxy-D-ribose, using a phosphorus pentoxide reagent.

Direct condensation of 2-deoxy-D-ribose (1) with mercaptans using the P4O10/H2O/Bu3N reagent in chloroform resulted in coupling at C-3 to give the anomeric mixtures of the corresponding pentopyranoses 2 and pentofuranoses 3. After acetylation with acetic anhydride in dry pyridine of these 3-alkylthio pentofuranoses, coupling with the nucleobases uracil, thymine, and cytosine in accordance with the Friedel-Crafts catalyzed silyl Hilbert-Johnson method yielded the acetylated D-erythro nucleosides 7 as anomeric mixtures, separable only by means of chromatography either before or after deprotection with ammonia. The nucleosides 8a-e were devoid of any activity against HSV-1 and HIV-1.     

Enhancing psychotherapy outcomes via providing feedback on client progress: a replication

Several systems have been developed to monitor and feedback information about a client's responses to psychotherapy as a method of enhancing client outcome. The current study divided 1020 clients into four groups (two experimental and two control) to determine if feedback regarding client progress, when provided to a therapist, affected client outcome and number of sessions attended. Results showed that feedback increased the duration of treatment and improved outcome for clients identified as potential treatment failures thereby replicating an earlier study using nearly identical methodology. Nearly twice as many clients in the feedback group achieved clinically significant or reliable change and fewer were classified as deteriorated by the time treatment ended. For those clients who were predicted to have a positive response to treatment, feedback to therapists resulted in an equal number of treatment sessions and equivalent outcomes compared to the no feedback controls. The results are discussed in terms of quality management in routine clinical practice and the need to base treatment decisions on clients' response to treatment rather than arbitrary session limits. Suggestions for additional research aimed at enhancing the effects of feedback on client outcome are made. Copyright © 2002 John Wiley & Sons, Ltd.     

Response of the goat carotid body to acute and prolonged hypercapnia

The effect of prolonged hypercapnia on carotid chemoreceptor discharge frequency has not been elucidated. In addition, the effect of acute hypercapnia on chemoreceptor discharge has not been determined in the goat, a species commonly used for ventilatory control studies. Therefore, we determined the effects of acute and prolonged normoxic-hypercapnia on single fiber output of the carotid body of chloralose anesthetized goats. The animals were paralyzed and artificially ventilated. The average acute response curve for 12 single fibers was linear over the range of 30-80 Torr PaCO2 with a mean slope of 0.115 +/- 0.057 (SD) imp.sec-1.Torr-1 PaCO2. Elevated discharge frequency was maintained during prolonged (up to 240 min, n = 11) steady-state hypercapnia (X PaCO2 = 85 Torr). No systematic time-dependent changes in afferent discharge frequency occurred during the period. The findings obtained during sustained hypercapnia are in contrast to the time-dependent increase in carotid body activity seen previously in our laboratory with prolonged normocapnic-hypoxia of up to 240 min duration.     

Monitoring of pancreatic graft perfusion by first passage radionuclide angiography

The perfusion of two pancreatic transplants were examined three times a week for the first five postoperative weeks by intravenous angiography using 99Tcm-pertechnetate. Worsening of the perfusion always preceded or was associated with deterioration of the pancreatic function. Accordingly, radionuclide angiography may have an important place in the systematic monitoring of pancreatic transplants in the critical postoperative period.     

The acceleration transducer – an assessment of its precision in comparison with a force displacement transducer

A new and simple acceleration transducer (ACT)–based system of neuromuscular monitoring has recently been introduced. The precision of this transducer has been evaluated as compared to a conventional force displacement transducer (FDT) in the present study. Ten progressions of spontaneous recovery from atracurium–induced block with simultaneous measurements using the ACT on one hand and the FDT on the other were studied. Five individuals undergoing elective surgery in modified neurolept anaesthesia and one ICU–patient requiring prolonged neuromuscular blockade, sedated with pentobarbital, were included. Measurements were carried out on the latter patient on 5 consecutive days. Train–of–four (TOF) stimulation was used, readings were given in twitch heights (TH) (Tl/control value), and when four responses were obtained in TOF–ratios (T4/T1). Linearity was achieved after logit–transformation and the values regressed on time for each progression of recovery. Analysis of variance was applied to the regressions for the TH and TOF–ratio readings of each transducer. No significant differences were found, either between variation due to differences between slopes or variation due to technical error between the two transducers. The study indicates that the ACT is equal to the FDT with regard to precision in clinical recordings on atracuriumrelaxed individuals.     

Spontaneous abortion following mid-trimester amniocentesis. Clinical significance of placental perforation and blood-stained amniotic fluid

The clinical significance of placental perforation and blood-stained amniotic fluid was studied in a group of 7238 Danish women undergoing mid-trimester amniocentesis for prenatal diagnosis under ultrasound guidance. The risk of spontaneous abortion was significantly increased both in pregnancies where the placenta was perforated and in those with blood-stained amniotic fluid. The risk estimate nearly doubled after placental perforation and more than doubled with a bloody tap. It is concluded that for women at relatively low risk of a fetal genetic abnormality, the indication of the amniocentesis should be reconsidered if a placental perforation is unavoidable.     

Hyperosmolarity selectively enhances IgE-receptor-mediated histamine release from human basophils

Increased osmotic pressure has been reported to cause non-cytotoxic histamine release (HR) from human basophils, as well as a potentation of HR induced by anti-IgE. In this study, the effects of hyperosmolar Na–K-acetate (300–600 mOsm/kg H₂O) on HR was studied in washed human blood cells from newborns, adult volunteers and patients with severe atopic dermatitis. These three patient groups represesented 3 very distinct populations with respect to total plasma IgE content, medians were <0.2 IU/ml, 20.5 IU/ml and 2508 IU/ml, respectively. Increasing osmolarity to 500 mOsm/kg H₂O caused little HR in the absence of other stimuli, whereas at 600 mOsm/kg H₂O a significant increase in spontaneous HR was seen. The HR induced by anti-IgE and Concanavalin A, acting through the IgE-receptor, was increased approximately twofold at 500 mOsM/kg H₂O. Responses were highly correlated to results at 300 mOsm/kg H₂O. The use of 600 mOsm/kg H₂O buffers caused a further increase in most, but not all blood samples. The potentiation of IgE-receptor-mediated HR when using hyperosmolar media was clearly independent of plasma IgE contents, and did not change the concentration-response to anti-IgE. In contrast, HR induced by the IgE-receptor-independent stimuli, Formyl-met-leu-phe and calcium ionophore A 23187, were not enhanced at all by incrased osmotic pressure. We conclude, that hyperosomolar media selectively enhance IgE-receptor-mediated HR. The use of hyperosmolar media may therefore be beneficial in a diagnostic application of washed blood HR assays use in allergy diagnosis.