Clinical trial: the effects of the proton pump inhibitor dexlansoprazole MR on daytime and nighttime heartburn in patients with non-erosive reflux disease.

BACKGROUND: The proportion of patients who respond to proton pump inhibitor (PPI) therapy is about 20% lower in those with non-erosive reflux disease (NERD) than in those with erosive oesophagitis. AIM: To assess efficacy and safety of dexlansoprazole MR, a PPI using Dual Delayed Release technology, in NERD patients. METHODS: In this 4-week, double-blind, placebo-controlled study, 947 NERD patients randomly received dexlansoprazole MR 30 mg, 60 mg or placebo once daily (QD). The percentages of 24-h heartburn-free days (primary) and nights without heartburn (secondary) were assessed from patients' daily diaries. Investigators also assessed symptoms. Patients completed validated quality of life and symptom severity questionnaires. RESULTS: Dexlansoprazole MR provided significantly greater median percentages of 24-h heartburn-free days (54.9% and 50.0% for the 30- and 60-mg doses vs. 17.5% for placebo, P < 0.00001) and nights without heartburn (80.8% and 76.9% vs. 51.7%, P < 0.00001 vs. placebo). Dexlansoprazole MR also reduced symptom severity. Quality of life improvements in patients receiving dexlansoprazole MR were consistent with clinical efficacy endpoints. Percentages of patients experiencing treatment-emergent adverse events were similar among groups. CONCLUSIONS: Dexlansoprazole MR 30 and 60 mg were superior to placebo in providing 24-h heartburn-free days and nights in NERD patients. Treatment was well tolerated.

High-field fractional quantum Hall effect in optical lattices.

We consider interacting bosonic atoms in an optical lattice subject to a large simulated magnetic field. We develop a model similar to a bilayer fractional quantum Hall system valid near simple rational numbers of magnetic flux quanta per lattice cell. Then we calculate its ground state, magnetic lengths, fractional fillings, and find unexpected sign changes in the Hall current. Finally we study methods for detecting these novel features via shot noise and Hall current measurements.

United Kingdom 'Crown' indemnity for medical negligence--an overview of the first 18 months of the new scheme.

This article describes the background to the introduction of 'Crown' indemnity and summarizes the operation of the scheme. It also makes clear the limited nature of the scheme and how it does not apply, for example, to independent contractors such as general medical and dental practitioners. Also described is the nature and operation of United Kingdom medical defence organizations such as the Medical Protection Society and the services which they continue to provide to medical and dental practitioners worldwide. Early indications suggest that the new government scheme is placing a very heavy financial burden on health authorities which already suffer from underfunding and tight budgetary control.

Inhibition of cold-promoted activation of the prothrombin time studies of new siliconized borosilicate collection tubes in normals and patients receiving warfarin.

Studies of the prothrombin time in normals and patients receiving oral anticoagulant therapy revealed a partial inhibition of the in vitro cold-promoted activation of Factor VII and shortening of the prothrombin time when blood was collected in a new commercial siliconized borosilicate tube (Becton-Dickinson, Rutherford, NJ, 6418 and 6419). The data collected with normal blood indicated that the cold-promoted activation was almost totally inhibited, while the patients had only a mean reduction of 50% of the cold-promoted activation. In pregnant patients there was no inhibition of the cold-promoted activation of the prothrombin time or Factor VII using the new siliconized tubes.

Circulating heparan sulfate anticoagulant in a patient with a fatal bleeding disorder.

We have identified a circulating, heparin-like anticoagulant in a patient with multiple myeloma (IgG4 lambda) who had serious clinically evident bleeding that contributed to his death. Purification of the patient's circulating coagulation inhibitor was accomplished by ammonium sulfate concentration, anion exchange chromatography, and affinity chromatography on protamine sulfate. Analysis of the purified inhibitor showed that it was a proteoglycan that comigrated with heparan sulfate on lithium acetate-agarose-gel electrophoresis and that it contained 39 per cent L-iduronic acid. Control samples of heparan sulfate and heparin contained 29 and 68 per cent L-iduronic acid, respectively. Functional coagulation studies revealed that the purified inhibitor had cofactor activity with antithrombin III that could be abolished by prior incubation with protamine sulfate or platelet factor 4. Recognition of the existence of this or of other similar inhibitors in bleeding patients is important because of the potential for treatment with agents such as protamine sulfate and platelet factor 4, which neutralize the anticoagulant effects of proteoglycans.

Inhibition of the cold activation of Factor VII and the prothrombin time.

Normal whole blood, collected and stored in borosilicate or commercial siliconized borosilicate tubes at 4 degrees C, undergoes a time-dependent activation of Factor VII and a shortening of the prothrombin time (PT). Addition of inhibitors to Factor XII fragments (corn Hageman factor inhibitor, CHFI) or to activated Factor XII (Cytochrome-C) inhibited in a concentration-dependent way the cold-promoted activation of Factor VII and the shortening of the PT. When celite was added to whole blood in polypropylene tubes at 4 degrees C, Factor VII was activated and the PT shortened. Preincubation of celite with CHFI or Cytochrome-C prevented the activation of Factor XII and the subsequent activation of Factor VII and the PT. These studies demonstrate the importance of Factor XII in the cold activation of Factor VII and shortening of the PT and indicate that inhibitors to activated Factor XII or XII fragments are useful in inhibiting in vitro shortening of the PT. These findings suggest that the development of a collection tube that prevents contact activation also would inhibit adequately the cold-promoted activation of the PT and Factor VII.

Nafcillin resistant Staphylococcus aureus: a possible community origin.

An increased incidence in nafcillin (semisynthetic penicillins) resistant Staphylococcus aureus (SR-SA), which peaked in January 1980, was noted in Columbus Children's Hospital (CCH), Columbus, Ohio. To investigate the source of this outbreak, we reviewed the susceptibility patterns of S. aureus strains isolated at CCH for a 12-month period (July 1979 to June 1980). A total of 773 isolates from 706 patients were investigated with a total of 40 patients colonized or infected with SR-SA, approximately 25% of which were diagnosed in the ambulatory clinics. These patients did not have any apparent previous contact with the inpatient unit or inpatient personnel. Eight nosocomial infections were also uncovered. The first appeared in December 1979. Our studies suggested that some SR-SA isolates may have originated in the community and these organisms may not be exclusive to the hospital environment, as was felt to be the case previously. We also determined that the baseline incidence for our hospital of SR-SA was approximately 2% of total S. aureus isolates. Only 35% of the SR-SA demonstrated resistance to multiple antibiotics. This report indicates that community and nosocomial S. aureus isolates should be monitored for nafcillin resistance. Vancomycin susceptibility should be tested on all isolates and reported for SR-SA in life-threatening infections.

Warfarin anticoagulation: difficulties in interpretation of the prothrombin time.

Studies of the prothrombin time in normals and patients receiving warfarin therapy revealed a marked shortening of the prothrombin time when the blood was collected in any type of collection tube other than a polypropylene tube. This shortening of the prothrombin time in patients receiving coumadin therapy was time and temperature dependent. This in-vitro shortening of the prothrombin time could lead to serious clinical errors involving dosage of warfarin derivatives to be administered to patients.

Cold-induced contact surface activation of the prothrombin time in whole blood.

Studies of the prothrombin time (PT) have revealed that contact with borosilicate or commercial siliconized borosilicate markedly shortens the PT. This shortening is related to the activation of the contact phase of blood coagulation. This shortening of the PT occurs in both normal whole blood and plasma when stored in borosilicate or siliconized borosilicate tubes at 4 degree C and to a lesser degree at room temperature. Studies indicated the importance of several coagulation factors in decreasing the PT. The PT did not change in blood deficient in factor XII or in plasma deficient in Fletcher factor or high molecular weight kininogen, while blood deficient in CI esterase inhibitor (CI INH) had the most profound shortening. Shortening of the PT correlated directly with increased levels of factor VII. When purified CI INH was added to normal blood, it markedly reduced the activation of factor VII and the shortening of the PT in a dose-related manner. These studies indicate the pivotal roles of the contact phase of coagulation in initiating activation of the PT and of CI INH in inhibiting the activation of the coagulation factor(s) responsible for the cold-promoted activation of factor VII.