Review article: the pharmacokinetics of rabeprazole in health and disease

Rabeprazole, a newly developed proton pump inhibitor, has been shown to be effective for the treatment of gastric and duodenal ulcers and for gastro-oesophageal reflux disease. It is a rapid and potent inhibitor of gastric H⁺,K⁺-ATPase, the gastric acid (proton) pump. The maximum plasma concentration ( C _max) and the area under the plasma concentration time curve ( AUC ) are linearly related to dose, while the time to maximum plasma concentration ( t _max) and elimination half-life ( t _½) are dose-independent. Rabeprazole is extensively metabolized in the liver via the cytochrome P450 enzyme system, and its metabolites are excreted primarily in the urine. Rabeprazole does not accumulate with repeated dosing. Its bioavailability is not influenced by the coingestion of either food or antacids. The pharmacokinetic profile of rabeprazole is substantially altered in the elderly and patients with stable compensated chronic cirrhosis; however, these alterations are not associated with clinically significant abnormalities in laboratory parameters or serious adverse events. The influence of severe decompensated liver disease on the pharmacokinetics of rabeprazole has not been assessed. The pharmacokinetic profile of rabeprazole is not significantly altered by renal dysfunction requiring maintenance haemodialysis. These findings suggest that dosage adjustment is not required in these special patient populations. Caution should be exercised, however, in patients with severe liver disease.     

PREVALENCE OF MICROALBUMINURIA IN NON-INSULIN-DEPENDENT DIABETES MELLITUS

The prevalence of microalbuminuria was assessed in 50 patients of non-insulin dependent diabetes mellitus. The mean age of patients was 52.1 ± 11.6 years and the duration of diabetes was 8.3 ± 6.8 years. Twenty (40%) patients had microalbuminuria. Microalbuminuria was more common in patients with a longer duration of diabetes (more than 5 years), a poor glycaemic control, and higher systolic blood pressure.KEY WORDS: Microalbuminuria, Diabetes mellitus, Diabetic nephropathy, Chronic renal failure     

Running as fast as they can: organizational changes in home health care

During the 1980s, as the health care industry experienced what observers have dubbed a revolution, the home health industry also experienced its own transformation. Utilizing three organizational theories (neoinstitutional, resource dependency and population ecology), the authors report on a study of a probability sample of 163 home health agencies (HHAs) that were interviewed in 1986 and again in 1987 on the effects of Medicare policy changes including prospective payment (DRGs). This study tests hypotheses concerning the influence of environmental factors (e.g., state policy and characteristics of the local market) and organizational characteristics of the HHA (e.g., tax status and Medicare reliance) in explaining the propensity of HHAs to be (or become) parts of chains and/or multi-facility systems; and to develop particular types of interorganizational relations. The paper discusses the results in the context of public policy changes and the implications for future research and practice.     

Bedside hemodynamic monitoring. Its value in the diagnosis of tamponade complicating cardiac surgery.

Cardiac tamponade may be a difficult clinical diagnosis in the early postoperative period in patients undergoing open-hear surgery, particularly when the anterior or lateral pericardium is left open. Bedside monitoring of intracardiac pressures and determination of a "pressure plateau" between right atrial, right ventricular diastolic, pulmonary arterial diastolic, and pulmonary capillary wedge pressures are useful in the early diagnosis of cardiac tamponade. The value of such hemodynamic monitoring in the diagnosis and treatment of cardiac tamponade in three patients with aorta-coronary artery bypass surgery in the early postoperative period is reported. Appropriate therapy, carried out on the basis of these studies, minimized the occurrence of further morbidity or possible death.     

Postoperative synergistic gangrene after spinal fusion

STUDY DESIGN: A case of synergistic necrotizing gangrenous fasciitis after spinal surgery is reported. OBJECTIVES: To describe this unusual complication, explain the rationale of treatment, and increase awareness of this serious postoperative complication. SUMMARY OF BACKGROUND DATA: Although several cases of postoperative synergistic necrotizing fasciitis have been reported, there are no previously reported cases of this condition after spinal surgery. METHODS: A rapidly progressive necrotizing spinal wound infection after fusion for degenerative disc disease was treated in a 39-year-old man. RESULTS: The infection was successfully treated with serial debridements, appropriate antibiotics, and hyperbaric wound oxygenation. CONCLUSIONS: The authors suggest adherence to the fundamental principles of treatment including radical surgical debridement and appropriate antibiosis for necrotizing gangrene after spinal surgery. In evaluation of aggressive spinal wound infections, diagnosis of synergistic necrotizing fasciitis should be kept in mind. Although hyperbaric wound oxygenation was implemented as an adjunct and appeared to aid in controlling the infection, its effect on outcome is not clear.     

Profile of non-compliance in lymphoblastic leukaemia

A nationwide study of intracellular drug metabolite concentrations in children prescribed 6-mercaptopurine for the treatment of lymphoblastic leukaemia was carried out to assess interpatient variability at a standardised dose. Nine children (2% of the total) had completely undetectable metabolites, indicative of non-compliance. Five were adolescents, but otherwise they had no obvious distinguishing characteristics. Not taking any 6-mercaptopurine at all is uncommon, but the problem cannot be predicted. The total number of children who do not comply cannot be determined from this study, but the nine children described represent only a fraction of these.     

3D MR DSA: effects of injection protocol and image masking

The purpose of this study was to investigate the effect on three-dimensional (3D) magnetic resonance digital subtraction angiography (MR DSA) images of various injection protocol parameters (ie, injection order, volume, and rate), as well as image masking. The pelves of 10 normal volunteers were scanned using seven different contrast agent volume/injection rate combinations. Subtraction of a precontrast mask image resulted in vascular image contrast improvements of between 4.0 and 7.7 times. Image quality and smaller vessel image contrast in the masked data decreased with increasing injection number. Data acquired with a high (0.150 mmol kg(-1)) volume yielded the highest quality images, although only small nonsignificant differences in image quality and large vessel conspicuity were found between images obtained using the high and medium (0.075 mmol kg(-1)) volumes. Images acquired with a low (0. 038 mmol kg(-1)) volume, while of lower image contrast, were judged to be of reasonable quality, especially when acquired as the first or second injection. Injection rate (1 ml s(-1), 2 ml s(-1), and 4 ml s(-1)) was not found to affect the images significantly, although selection of an injection rate that gave an injection duration of approximately 10 seconds tended to give better vascular image contrast. Based on these data, a series of escalating volumes for multi-injection examination is proposed. J. Magn. Reson. Imaging 2000;12:476-487.     

Immune responses against SARS-coronavirus nucleocapsid protein induced by DNA vaccine

The nucleocapsid （N） protein of SARS-coronavirus （SARS-CoV） is the key protein for the formation of the helical nucleocapsid during virion assembly. This protein is believed to be more conserved than other proteins of the virus, such as spike and membrane glycoprotein. In this study, the N protein of SARS-CoV was expressed in Escherichia coli DHSalpha and identified with pooled sera from patients in the convalescence phase of SARS. A plasmid pCI-N, encoding the full-length N gene of SARS-CoV, was constructed. Expression of the N protein was observed in COS1 cells following transfection with pCI-N. The immune responses induced by intramuscular immunization with pCI-N were evaluated in a murine model. Serum anti-N immunoglobutins and splenocytes proliferative responses against N protein were observed in immunized BALB/c mice. The major immunoglobulin G subclass recognizing N protein was immunoglobulin G2a, and stimulated splenocytes secreted high levels of gamma interferon and IL-2 in response to N protein. More importantly, the immunized mice produced strong delayed-type hypersensitivity （DTH） and CD^8＋ CTL responses to N protein.