Usefulness of clinical pathway for community-acquired pneumonia as both an educational and a cost-management tool--an intervention study to compare the usefulness of management with a critical pathway to historical control of conventional management]

To delineate the usefulness of a clinical pathway for community-acquired pneumonia (CAP) as an educational tool as well as a cost management tool, we conducted a prospective controlled trial including a historical control group. Consecutive CAP patients classified under Category 3 of the American Thoracic Society and admitted to our hospital were evaluated. Using the clinical pathway method, 42 patients were managed between April and December 2000 as the intervention group, and 33 patients received conventional management between April and December 1999 as a historical control. For the intervention group, the clinical pathway, which was a time-task matrix formatted with consideration for guidance for disease treatment, laboratory tests, physical examinations, oxygen saturation monitoring, ambulation, diet, education for the patient and clinical outcomes, was implemented. We determined (1) educational effect, measured using reduction of delay caused by physicians; (2) quality of clinical practice, measured using the success rate of the initial antimicrobial therapy and readmission rate; and (3) economic efficacy, measured using health care cost and length of hospital stay. The delay caused by physicians was reduced by 16% in the Intervention Group (5% vs. 21%; p = 0.045). The success rates of initial antimicrobial therapy in the two groups were similar (85.7% vs. 84.8%). In the intention-to-treat set, the median value of health care cost was reduced by yen 48,055 (yen 277,460 vs. yen 325,515; p = 0.017) and the median length of a hospital stay was shortened by 3 days (8 vs. 11 days; p = 0.0007) in the Intervention Group. In conclusion, the clinical pathway had an educational effect on physicians regarding the management of hospitalized patients with community-acquired pneumonia as well as on the cost management.     

Changes in mRNA expression of MMP-2 in the Müllerian duct of chicken embryo

Although asymmetric development of the ovary and the oviduct is a unique characteristic in birds, the mechanism of asymmetric development still remains unclear. Recently, degradation of extracellular matrix has been suggested as an important factor related to the regression of the Müllerian duct in mammals. The present study was conducted to examine a possible role of metalloproteinase-2 (MMP-2) in the regression of the right Müllerian duct in the developing chicken embryo. Morphological changes in the Müllerian ducts were studied on day 15 of incubation and mRNA expresseion of MMP-2 was studied on days 12, 15, and 18 of incubation. Morphological observation demonstrated the disappearance of basement membrane in the right Müllerian duct which undergoes the regression. RT-PCR analysis showed that MMP-2 mRNA expression of the right Müllerian duct increased on days 15 and 18 of incubation coincidently with the time of regression. In the right Müllerian duct, regression was prevented by diethylstilbestrol treatment on day 4 of incubation and a coincident decrease in MMP-2 expression was observed when compared to the control group. These results suggest that MMP-2 may be involved in the regression of the right Müllerian duct in the female embryos of the chicken.     

Genes for systemic vascular complications are differentially expressed in the livers of Type 2 diabetic patients

Aims/hypothesis Type 2 diabetes is characterised by excessive hepatic glucose production and frequently leads to systemic vascular complications. We therefore analysed the relationship between the gene expression profile in the liver and the pathophysiology of Type 2 diabetes.Methods Liver biopsy samples were obtained from twelve patients with Type 2 diabetes and from nine non-diabetic patients. To assay gene expression globally in the livers of both groups, we made complementary DNA (cDNA) microarrays consisting of 1080 human cDNAs. Relative expression ratios of individual genes were obtained by comparing cyanine 5-labelled cDNA from the patients with cyanine 3-labelled cDNA from reference RNA from the liver of a non-diabetic patient.Results On assessing the similarities of differentially expressed genes, the gene expression profiles of the twelve diabetic patients formed a separate cluster from those of the non-diabetic patients. Of the 1080 genes assayed, 105 (9.7%) were up-regulated and 134 (12%) were down-regulated in the diabetic livers (p<0.005). The genes up-regulated in the diabetic patients included those encoding angiogenic factors such as vascular endothelial growth factor, endothelin and platelet-derived growth factor. They also included TGF superfamily genes such as TGFA and TGFB1 as well as bone morphogenetic proteins. Among the down-regulated genes in the diabetic patients were molecules defending against stress, e.g. flavin-containing monooxygenase and superoxide dismutase.Conclusions/interpretation These findings suggest that livers of patients with Type 2 diabetes have gene expression profiles indicative of an increased risk of systemic vascular complications.Electronic Supplementary Material Supplementary material is available in the online version of this article at Abbreviations aRNA antisense RNA - BMP bone morphogenetic protein - cDNA complementary DNA - Cy cyanine - FMO flavin-containing monooxygenase - NASH non-alcoholic steatohepatitis - PDGF platelet-derived growth factor - SSC standard saline citrate - SOD superoxide dismutase - VCAM vascular cell adhesion molecule - VEGF vascular endothelial growth factor     

Chronic persistent Epstein-Barr virus infection of natural killer cells and B cells associated with granular lymphocytes expansion

B lymphocytes and epithelial cells are the only cell types known to be infected with Epstein-Barr virus (EBV) in normal individuals. Rarely, EBV also infects other cells, including natural killer (NK) cells, almost always in the context of fatal leukaemias or lymphoproliferative disorders. We report on a 6-year-old previously healthy girl who developed fevers and liver function abnormalities for 3 months. The peripheral blood revealed an abnormal expansion of large granular lymphocytes, comprising 24% of the white blood cells. Flow cytometric analysis of the peripheral blood mononuclear cells showed an abnormal increase of CD16-positive NK cells, 62% of which were EBV-infected by in situ EBER-1 hybridization. The circulating B cells were normal in number, but 18% were infected with EBV by in situ EBER-1 hybridization. Approximately 2 years after resolution of all symptoms and continued good health, 35% of the circulating mononuclear cells were EBV-infected, indicative of persistent expansion of EBV-infected cells. We conclude that abnormal expansions of EBV-infected NK and B cells can be associated with a chronic benign course.     

Oral OPC-8212 for the treatment of congestive heart failure: Hemodynamic improvement and increased exercise capacity

Summary The chronic effects of the oral administration of OPC-8212 (3,4-DIHYDRO-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone) on resting hemodynamics and exercise capacity were assessed in 15 patients with congestive heart failure (NYHA II–IV). Doses of 30 or 60 mg per day were given per os over 3.0 weeks on average (range 2–6 weeks). Multigated radionuclide ventriculography and multistage exercise testing were performed before and during OPC-8212 therapy to assess the changes in left ventricular volume and exercise capacity respectively. Systolic blood pressure showed a slight increase (from 123±3 to 129±4 mmHg) during OPC-8212 therapy, while heart rate was unchanged (69±3 vs 67±3 beats/min). The left ventricular end-diastolic volume index decreased from 127±9 to 107±7 ml/m², and ejection fraction and the P/V index (the ratio of peak systolic pressure to left ventricular end-systolic volume index) increased during OPC-8212 therapy (from 27%±3% to 30%±4% and from 1.5±0.2 to 2.0±0.3 mmHg/ml/m² respectively). NYHA functional class was improved in 9 of 15 patients, and the average peak work load achieved during exercise testing increased from 27±6 to 47±7 W. No significant adverse effect was observed in any patient. These results indicate that OPC-8212 enhances the inotropic state and, hence, reduces heart size with no change in heart rate. Moreover, it increases exercise capacity. Thus, OPC-8212 is an inotropic agent with promise for application in the long-term treatment of congestive heart failure.     

Repeated piezoelectric lithotripsy for gallstones with and without ursodeoxycholic acid dissolution: A multicenter study

The use of bile acid dissolution therapy in extracorporeal shockwave lithotripsy of gallstones, remains controversial. Our study examined whether chemolitholysis after sufficient disintegration enhanced stone clearance within 6 months of the first lithotripsy. A total of 143 patients who developed one to three radiolucent stones measuring⪯30 mm in diameter were randomly separated into two treatment groups: 47% were given lithotripsy alone, and 53% lithotripsy plus ursodeoxycholic acid (UDCA). Repeated piezoelectric lithotripsy was given, with no limit on the total number of treatment sessions, to pulverize or disintegrate stones into fragments<3 mm. Stones were disintegrated in 97% of all patients, and the fragments were ⪯2 mm in 50% of these patients. According to an intention-to-treat analysis, 52% in the lithotripsy alone group and 58% in the UDCA group were free of stones 6 months after the first lithotripsy (P=0.61). Of the patients with fragments⪯2 mm, 71% in the former and 86% in the latter group were free of stones 6 months after the first lithotripsy, with no significant difference between the groups. Biliary pain occurred in 25% of all patients, including 3 with acute cholecystitis. We concluded that the sufficient disintegration of gallstones achieved with repeated lithotripsy enhanced the early clearance of fragments, regardless of whether chemolitholysis was employed.     

Relation between white blood cell counts and myocardial reperfusion in patients with recanalized anterior acute myocardial infarction.

BACKGROUND: The clinical significance of the white blood cell (WBC) count on admission in relation to the duration of ischemia in acute myocardial infarction (AMI) remains unclear. METHODS AND RESULTS: The relationship of the WBC count on admission to myocardial reperfusion was examined in 135 patients with recanalization of an anterior AMI within 6 h of symptom onset. Patients were classified according to the WBC count on admission: Group L (n=75), WBC count <12,000 cells/mm(3) and group H (n=60), WBC count >or=12,000 cells/mm(3). Peak creatine kinase (CK) was higher and impaired myocardial reperfusion, defined as a myocardial blush grade of 0/1, was more frequent in group H than in group L. Among the patients in group H, those with early (3 h) recanalization; however, peak CK and the incidence of impaired myocardial reperfusion were similar in these subgroups of patients. Multivariate analysis showed that WBC count >or=12,000 cells/mm(3) on admission was an independent predictor of impaired myocardial reperfusion in patients with early recanalization (odds ratio 7.9, p=0.04), but not in those with late recanalization. CONCLUSIONS: A higher WBC count may be associated with progression of myocardial damage after recanalization in patients with early recanalization of an anterior AMI.     

Evaluation of the efficacy of an Helicobacter pylori eradication treatment for idiopathic thrombocytopenic purpura patients]

The relationship between Helicobacter pylori (H. pylori) and gastric diseases (e.g. peptic ulcer, MALT lymphoma, and stomach cancer) has been widely accepted. Recent studies have also suggested an association between H. pylori infection and idiopathic thrombocytopenic purpura (ITP). In this study, an H. pylori eradication treatment was administered to 20 ITP patients and elucidated for its effectiveness. Among those 20 patients, H. pylori infection was confirmed in 17 (85%) through a C14 urea breath test, a rapid urease test, or a culture examination of a biopsied sample obtained by gastrointestinal endoscopy. Although the other 3 were negative to H. pylori, the H. pylori eradication treatment was also attempted because no other effective treatments had been established at the time of this study. In the H. pylori eradication treatment, lansoprazole (LPZ) 60 mg bid, amoxicillin (AMPC) 1500 mg bid, and clarithromycin (CAM) 400 mg bid were given to each patient for 7 days. For 4 cases, CAM was replaced with metronidazole (MNZ) 750 mg bid. The patients whose H. pylori infection was not eradicated after the first treatment received the re-eradication treatment with LPZ 60 mg bid, AMPC 1500 mg bid, and MNZ 750 mg bid for 7 days. After the treatments, the success of eradicating H. pylori was confirmed in all 17 H. pylori positive patients. In addition, platelet recovery was obtained in 11/20 patients (55%), which included 2 H. pylori negative patients and 2 patients whose H. pylori eradication was not successful after the first treatment. No relationship was found between the eradication effectiveness and the following clinical parameters: age, gender, previous therapies, disease duration, presence of anti-nucleus antibody, endoscopic atrophic change in the stomach, or kinds of antibiotics used for the treatment. These results support the efficacy of an H. pylori eradication treatment for ITP patients. A noteworthy result of this study was that an increase of platelet count was observed not only in H. pylori positive ITP patients, but also in 2 out of 3 H. pylori negative ITP patients after H. pylori eradication. Further studies are required to elucidate the efficacy of H. pylori eradication therapy in the patients negative for H. pylori.     

Very-low-calorie diet-induced weight reduction reverses impaired growth hormone secretion response to growth hormone-releasing hormone, arginine, and L-dopa in obesity

To determine whether impaired growth hormone (GH) secretion in obese subjects is a consequence of obesity or a pre-existing pituitary-hypothalamic disorder, we measured (1) plasma GH response to growth hormone-releasing hormone (GRH; 1 microgram/kg body weight [BW]), arginine (0.5 g/kg BW), and L-dopa (500 mg); and (2) plasma glucose, insulin, and free fatty acids (FFA) in obese subjects before and after weight reduction due to very-low-calorie diet therapy using Optifast (240 kcal/d for 8 to 12 weeks). Body weight and body mass index (BMI) values before and after weight reduction were 87.2 +/- 4.1 kg and 34.5 +/- 0.9 kg/m2, and 67.8 +/- 2.7 kg and 27.0 +/- 0.4 kg/m2, respectively. GH response to GRH, arginine, and L-dopa in obese subjects was markedly impaired before weight reduction, whereas significantly increased responses were noted after weight reduction (P less than .01). Impaired integrated GH response to GRH, arginine, and L-dopa in obese subjects was significantly restored after weight reduction (P less than .01). Plasma glucose levels did not change, while plasma insulin and FFA levels decreased significantly after weight reduction (P less than .01, P less than .05). There was no significant correlation between integrated GH response to these three stimuli and plasma levels of glucose, insulin, and FFA, respectively. The reversibility of GH response to all three stimuli after weight reduction suggests that impaired GH secretion is a consequence of obesity rather than a pre-existing pituitary-hypothalamic disorder.     

Thrombophilic dysfibrinogen Tokyo V with the amino acid substitution of gammaAla327Thr: formation of fragile but fibrinolysis-resistant fibrin clots and its relevance to arterial thromboembolism

Thrombophilic dysfibrinogen Tokyo V was identified in a 43-year-old man with recurrent thromboembolism. Based on analyses of the patient fibrinogen genes, the amino acid sequence of the aberrant fibrinogen peptide, and deglycosylation experiments, fibrinogen Tokyo V was shown to have an amino acid substitution of gamma Ala327Thr and possibly extra glycosylation at gamma Asn325 because the mutation confers the N-linked glycosylation consensus sequence Asn-X-Thr. The mutation resulted in impaired function and hypofibrinogenemia (hypodysfibrinogen). Polymerization of fibrin monomers derived from patient fibrinogen was severely impaired with a partial correction in the presence of calcium, resulting in very low clottability. Additionally, a large amount of soluble cross-linked fibrin was formed upon thrombin treatment in the presence of factor XIII and calcium. However, Tokyo V-derived fibrin was resistant to degradation by tissue plasminogen activator (tPA)-catalyzed plasmin digestion. The structure of Tokyo V fibrin appeared severely perturbed, since there are large pores inside the tangled fibrin networks and fiber ends at the boundaries. Taken together, these data suggest that Tokyo V fibrin clots are fragile, so that fibrinolysis-resistant insoluble fibrin and soluble fibrin polymers may be released to the circulation, partly accounting for the recurrent embolic episodes in the patient.