Laparoscopic underrunning of bleeding duodenal ulceration: a minimalist approach to therapy

Extrapontine myelinolysis is a rare and serious disorder characterized by patches of demyelination in certain areas of the brain. Common sites of involvement are the basal ganglia and the thalamus. The patient most often presents with behavioural abnormalities, including mutism, and extrapyramidal symptoms and signs. The diagnosis is established by magnetic resonance imaging. It usually carries a grave prognosis. The pathogenesis seems to be related to profound hyponatremia that is corrected with infusions of saline. We report a case that underwent surgical removal of a pituitary tumour and subsequently was treated with desmopressin. Probably due to an overdose of this antidiuretic hormone, she became obtunded and was found to have profound hyponatremia. This was corrected with infusions of saline, mostly isotonic. She later developed mental disorientation and mutism, and magnetic resonance imaging demonstrated myelinolysis in the basal ganglia. In the course of several months, she has made some recovery, though still demonstrating some memory deficit.     

Toward a more clinically valid approach to therapy research.

Despite the advances in psychotherapy outcome research, findings are limited because they do not fully generalize to the way therapy is conducted in the real world. Research's clinical validity has been compromised by the medicalization of outcome research, use of random assignment of clients without regard to appropriateness of treatment, fixed number of therapy sessions, nature of the therapy manuals, and use of theoretically pure therapies. The field needs to foster a more productive collaboration between clinician and researcher; study theoretically integrated interventions; use process research findings to improve therapy manuals; make greater use of replicated clinical case studies; focus on less heterogeneous, dimensionalized clinical problems; and find a better way of disseminating research findings to the practicing clinician. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A protocol illustrating a competency-based approach to cognitive therapy.

Presents a competency-based approach (CBA) that divides treatment into 9 distinct stages. These are (1) orientation, (2) basic self-observation skills (SBSs), (3) intermediate SBSs, (4) advanced SBSs, (5) hypothesis formulation and intervention planning, (6) test hypothesis and active intervention, (7) test development and alternative strategies, (8) test alternative strategies, and (9) termination. Using a CBA, clients are not allowed to move to a more advanced treatment stage until all criteria of the less advanced stage are met. The CBA seeks to reframe therapy and depathologize the process by focusing on new learning rather than unlearning. The CBA facilitates the formation of a collaborative therapeutic relationship and enhances clients' confidence in the therapeutic process and their own ability to learn. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Antagonists of the platelet P2T receptor: a novel approach to antithrombotic therapy

The platelet P2T receptor plays a major role in platelet aggregation, and its antagonists are predicted to have significant therapeutic potential as antithrombotic agents. We have explored analogues of adenosine triphosphate (ATP), which is a weak, nonselective but competitive P2T receptor antagonist. Modification of the polyphosphate side chain to prevent breakdown to the agonist adenosine diphosphate (ADP) and substitution of the adenine moiety to enhance affinity and selectivity for the P2T receptor led to the identification of 10e (AR-C67085MX), having an IC50 of 2.5 nM against ADP-induced aggregation of human platelets. Compound 10e was the first very potent antagonist of the P2T receptor, with a selectivity for that subtype of the P2 receptor family of >1000-fold. Further modification of the structure produced compound 10l (AR-C69931MX) having an IC50 of 0.4 nM. In vivo, at maximally effective antithrombotic doses, there is little prolongation of bleeding time (1.4-fold), which is in marked contrast to the 5-6-fold found with GPIIb/IIIa antagonists.     

An aggressive approach to HIV antiretroviral therapy

The introduction of highly active antiretroviral therapy offers the first real hope of durable control of HIV infection and prevention of clinical sequelae. But success hinges on early and complete suppression of viral replication. That demands near-perfect adherence to a complex regimen involving three or more drugs, each with its own dosage and dietary requirements.     

Selective peptidic and peptidomimetic inhibitors of Candida albicans myristoylCoA: protein N-myristoyltransferase: a new approach to antifungal therapy

MyristoylCoA: protein N-myristoyltransferase (NMT) catalyzes the cotranslational covalent attachment of a rare cellular fatty acid, myristate, to the N-terminal Gly residue of a variety of eukaryotic proteins. The myristoyl moiety is often essential for expression of the biological functions for these proteins. Attachment of C14:0 alone provides barely enough hydrophobicity to allow stable association with membranes. The partitioning of N-myrisotylproteins is therefore often modulated by "switches" that function through additional covalent or noncovalent modifications. Candida albicans, the principal cause of systemic fungal infection in immunocompromised humans, contains a single NMT gene that is essential for its viability. The functional properties of the acylCoA binding site of human and C. albicans NMT are very similar. However, there are distinct differences in their peptide binding sites. An ADP ribosylation factor (Arf) is included among the few cellular protein substrates of the fungal enzyme. Alanine scanning mutagenesis of an octapeptide derived from an N-terminal Arf sequence (GLYASKLS-NH2) disclosed that Gly1, Ser5, and Lys6 play predominant roles in binding. ALYASKLS-NH2 is an inhibitor competitive for peptide [Ki(app) = 15.3 +/- 6.4 microM] and noncompetitive for myristoylCoA. Remarkably, replacement of the N-terminal tetrapeptide with an 11-aminoundecanoyl group results in a competitive inhibitor (11-aminoundecanoyl-SKLS-NH2) that is approximately 40-fold more potent [Ki(app) = 0.40 +/- 0.03 microM] than the starting octapeptide. Removal of Leu-Ser from the C-terminus generates a competitive dipeptide inhibitor (11-aminoundecanoyl-SK-NH2) with a Ki(app) of 11.7 +/- 0.4 microM, equivalent to that of the starting octapeptide. A derivative dipeptide inhibitor containing a C-terminal N-cyclohexylethyl lysinamide moiety has the advantage of being more potent (IC50 = 0.11 +/- 0.03 microM) and resistant to digestion by cellular carboxypeptidases. Rigidifying the flexible aminoundecanoyl chain results in very potent general NMT inhibitors (IC50 = 40-50 nM). Substituting a 2-methylimidazole for the N-terminal amine and adding a benzylic alpha-methyl group with R stereochemistry to the rigidifying element produces even more potent inhibitors (IC50 = 20-50 nM) that are up to 500-fold selective for the fungal compared to human enzyme. A related less potent member of this series of compounds is fungistatic. Its growth inhibitory effects are associated with a reduction in cellular protein N-myristoylation, judged using cellular Arf as a reporter. These studies establish that NMT is a new antifungal target.     

Qualitative approach: a contribution to nursing

This paper focus on some characteristics of the qualitative methodology. Some of these methods are explored such as: participatory research, phenomenology, grounded theory and ethnography critical theory Perspectives of their utilization in nursing research are examined.     

Combination drug therapy in hypertension: a rational approach for the pharmacist

Knowledge of precise head kinematics during whiplash trauma is important for identifying possible injury mechanisms and their prevention. This study reports a comprehensive data set describing head kinematic response to horizontal accelerations simulating whiplash. Seven isolated fresh human cervical spine specimens (C0 to T1 or C7), each carrying a surrogate head designed to represent a 50th percentile human head, were mounted on the sled and subjected to incremental trauma by horizontal sled accelerations of 2.5, 4.5, 6.5, 8.5, and 10.5 g. Sled and head kinematics were measured with potentiometers and accelerometers. The incremental sled accelerations resulted in average (standard deviations) sled velocity changes (delta V) ranging from 5.8 (0.2) to 15.8 (0.2) km/h. Generally, all the peak head kinematic parameters increased with increasing sled acceleration, except for the peak head angular displacement, which decreased. In the initial phase of a whiplash trauma, the head translated posteriorly with respect to T1, without rotation. In the later phase, the head rotated backwards, but much less than its physiological limit. Maximum head rotation of 31.5 (23.9) degrees occurred in a 2.5 g trauma class, and this was less than the maximum physiological head extension of 55.1 (13.3) degrees. Head kinematics expressed in the T1 or shoulder coordinate system is better suited to study potential neck injury in whiplash.     

A gene therapy approach to regulated delivery of erythropoietin as a function of oxygen tension

Current therapy for several forms of anemia involves a weekly regime of multiple subcutaneous injections of recombinant human erythropoietin (hEpo). In an effort to provide a physiologically regulated administration of erythropoietin, we are developing cell lines genetically engineered to release hEpo as a function of oxygen tension. C2C12 cells were transfected using a vector containing the hEpo cDNA driven by the hypoxia-responsive promoter to the murine phosphoglycerate kinase gene. In vitro, these cells showed a threefold increase in hEpo secretion as oxygen levels were shifted from 21% to 1.3% oxygen. To test in vivo response, C2C12-hEpo cells were encapsulated in a microporous membrane and implanted subcutaneously on the dorsal flank of DBA/2J mice. On average, serum hEpo levels in animals exposed to 7% oxygen were two-fold higher than values seen in their control counterparts kept at 21% oxygen. Similar studies employing rats confirmed that hEpo delivery is regulated as a function of oxygen tension. These results suggest the feasibility of developing an oxygen-regulated, encapsulated cell-based system for hEpo delivery.     

Constraint-induced movement therapy: A new approach to treatment in physical rehabilitation.

Constraint-Induced (CI) Movement Therapy is a new approach to the rehabilitation of movement, based on research in neuroscience and behavioral psychology, that has been shown in controlled experiments to greatly increase the amount of use of an impaired upper extremity in chronic stroke patients in both the laboratory and the real world. CI Therapy consists of a family of techniques that induce stroke patients to greatly increase their use of an affected upper extremity for many hours a day over 10 to 14 consecutive days. The signature technique involves restricting the contralateral arm in a sling and training the affected arm. This commentary reviews the animal and human research and the theoretical formulation on which CI Therapy is based. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Combined therapy: A cognitive psychoanalytic approach.

Contends that cognitive-psychoanalytic clinical and theoretical considerations support a rationale for combined therapy. The interpenetrative transactions of the individual and group sessions delineate irrational beliefs and belief systems based on unrealistic expectations of threat and injury. The reconstructive aim is to resolve the members' idiosyncratically evolved psychopathology to whatever extent is possible. Detailed probings and introspection are more characteristic of the individual sessions, while outer-directed behavior and defensive engagements are more typical of the group. The complementarity of each modality provides a unified, integrated, therapeutic experience. (7 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)