Effect of upper gastrointestinal endoscopy on circulation in the elderly.

BACKGROUND: Upper gastrointestinal endoscopy in the elderly is increasingly becoming more common, despite the possibility that a minimal load on the circulation can cause serious complications such as shock and cardiac arrest. OBJECTIVE: The effects of endoscopy on the heart and the possibility of predicting circulatory accidents were studied using natriuretic peptide levels. METHODS: The patients were randomly chosen according to their age and divided into an elderly group (over 60 years of age, 64 patients) and a young group (under 30 years of age, 20 patients). The patients in the elderly group were further subdivided into two groups based on the presence or absence of circulatory complications (46 patients with circulatory complications and 18 without complications). The load on the heart was evaluated by measuring human atrial natriuretic peptide (hANP) and human brain natriuretic peptide (hBNP) which are secreted by the myocardial cells in response to cardiac load. Specimens were obtained before and after endoscopy. RESULTS: The hANP level was significantly higher after endoscopy in the elderly group, regardless of the presence or absence of circulatory complications. No significant difference was observed in the hBNP level. No significant increase in hANP or hBNP levels was observed after endoscopy in the young group. CONCLUSIONS: These observations suggest an increased atrial load during endoscopy in the elderly. The increase in pulse rate during endoscopy is one possible cause of atrial load. Therefore, the risk of circulatory system damage must be recognized when endoscopy is performed in the elderly. The measurement of plasma hANP and hBNP levels may provide effective indices for evaluating cardiac load during endoscopy.     

A CASE OF CHOLESTEROSIS OF THE COMMON BILE DUCT DIAGNOSED BY PERORAL CHOLANGIOSCOPY

We experienced a case of cholesterosis of the common bile duct in which peroral cholangioscopy (POCS) was very useful for making a diagnosis. The patient was a 66‐year‐old man. He was admitted for examination of an asymptomatic mass in the pancreas. The mass was diagnosed as a serous cystic tumor of the pancreas. While examining the tumor, endoscopic retrograde cholangiopancreatography (ERCP) incidentally revealed a 7 mm irregular filling defect in the distal common bile duct. EST was then performed, followed by POCS, which revealed a clump of yellowish‐white Ip or Isp polyps in the distal bile duct. Histological examination of biopsy specimens taken under direct vision gave a diagnosis of cholesterol polyps containing foamy cells. POCS was useful for allowing direct observation of the characteristic color of cholesterol polyps, and for obtaining biopsy specimens under direct vision.     

Amniotic membrane immobilized poly(vinyl alcohol) hybrid polymer as an artificial cornea scaffold that supports a stratified and differentiated corneal epithelium

Poly(vinyl alcohol) (PVA) is a biocompatible, transparent hydrogel with physical strength that makes it promising as a material for an artificial cornea. In our previous study, type I collagen was immobilized onto PVA (PVA-COL) as a possible artificial cornea scaffold that can sustain a functional corneal epithelium. The cellular adhesiveness of PVA in vitro was improved by collagen immobilization; however, stable epithelialization was not achieved in vivo. To improve epithelialization in vivo, we created an amniotic membrane (AM)-immobilized polyvinyl alcohol hydrogel (PVA-AM) for use as an artificial cornea material. AM was attached to PVA-COL using a tissue adhesive consisting of collagen and citric acid derivative (CAD) as a crosslinker. Rabbit corneal epithelial cells were air-lift cultured with 3T3 feeder fibroblasts to form a stratified epithelial layer on PVA-AM. The rabbit corneal epithelial cells formed 3-5 layers of keratin-3-positive epithelium on PVA-AM. Occludin-positive cells were observed lining the superficial epithelium, the gap-junctional protein connexin43-positive cells was localized to the cell membrane of the basal epithelium, while both collagen IV were observed in the basement membrane. Epithelialization over implanted PVA-AM was complete within 2 weeks, with little inflammation or opacification of the hydrogel. Corneal epithelialization on PVA-AM in rabbit corneas improved over PVA-COL, suggesting the possibility of using PVA-AM as a biocompatible hybrid material for keratoprosthesis.     

SARS-CoV spike protein-expressing recombinant vaccinia virus efficiently induces neutralizing antibodies in rabbits pre-immunized with vaccinia virus

A vaccine for severe acute respiratory syndrome (SARS) is being intensively pursued against its re-emergence. We generated a SARS coronavirus (SARS-CoV) spike protein-expressing recombinant vaccinia virus (RVV-S) using highly attenuated strain LC16m8. Intradermal administration of RVV-S into rabbits induced neutralizing (NT) antibodies against SARS-CoV 1 week after administration and the NT titer reached 1:1000 after boost immunization with RVV-S. Significantly, NT antibodies against SARS-CoV were induced by administration of RVV-S to rabbits that had been pre-immunized with LC16m8. RVV-S can induce NT antibodies against SARS-CoV despite the presence of NT antibodies against VV. These results suggest that RVV-S may be a powerful SARS vaccine, including in patients previously immunized with the smallpox vaccine.     

Comparative in-vitro activities of newer cephalosporins cefclidin, cefepime, and cefpirome against ceftazidime- or imipenem-resistant Pseudomonas aeruginosa.

Three hundred and thirty-four recent clinical isolates of Pseudomonas aeruginosa were examined for susceptibility to cefclidin, cefepime, and cefpirome. Of these strains, 28.7% were resistant to ceftazidime, and 23.4% were resistant to imipenem. About half of those resistant to ceftazidime were also resistant to imipemem. Although 37.4% and 59.6% of the isolates were resistant to cefepime and cefpirome respectively, and most or all ceftazidime-resistant strains showed resistance to cefepime and cefpirome, only 3.9% were resistant to cefclidin. Ceftazidime-resistant, but cefclidin-susceptible, P. aeruginosa produced high levels of chromosomal cephalosporinases. Of the compounds tested, cefclidin showed the lowest affinity for these enzymes, suggesting that its high activity against P. aeruginosa resistant to several beta-lactams was mainly due to its high resistance to enzymatic hydrolysis. Thirteen strains resistant to cefclidin were also resistant to both cefepime and cefpirome, and eight and three of these strains were resistant to ceftazidime and imipenem, respectively. A penicillinase, which hydrolyzed cefclidin, was detected in the cefclidin-resistant P. aeruginosa, which was similar to the OXA-1 beta-lactamase.     

In vitro and in vivo antifungal activities of ER-30346, a novel oral triazole with a broad antifungal spectrum.

ER-30346 is a novel oral triazole with a broad spectrum of potent activity against a wide range of fungi. ER-30346, with MICs at which 90% of the strains tested are inhibited (MIC90s) ranging from 0.025 to 0.78 microgram/ml, was 4 to 32 times more active than itraconazole, fluconazole, and amphotericin B against Candida albicans, Candida parapsilosis, and Candida glabrata. Against Candida tropicalis, ER-30346, with an MIC90 of 12.5 micrograms/ml, was 2 to > 8 times more active than itraconazole and fluconazole, but was 16 times less active than amphotericin B. ER-30346 (MIC90, 0.78 microgram/ml) was four to eight times more active than fluconazole and amphotericin B and had activity comparable to that of itraconazole against Trichosporon beigelli. The MIC90s of ER-30346 were 0.10 microgram/ml for Cryptococcus neoformans and 0.39 microgram/ml for Aspergillus fumigatus. ER-30346 was 2 to 8 times more active than itraconazole and amphotericin B and 32 to > 256 times more active than fluconazole. ER-30346 also showed good activity against dermatophytes, with MICs ranging from 0.05 to 0.39 microgram/ml, and its activity was comparable to or 2 to 16 times higher than those of itraconazole and amphotericin B and > 32 times higher than that of fluconazole. In vivo activity was evaluated with systemic infections in mice. Against systemic candidiasis and cryptococcosis, ER-30346 was comparable in efficacy to fluconazole and was more effective than itraconazole. Of the drugs tested, ER-30346 was the most effective drug against systemic aspergillosis. We studied the levels of ER-30346 in mouse plasma. The maximum concentration of drug in plasma and the area under the concentration-time curve for ER-30346 showed good linearity over a range of doses from 2 to 40 mg/kg of body weight.     

E-0702, a new cephalosporin, is incorporated into Escherichia coli cells via the tonB-dependent iron transport system.

E-0702, a new cephalosporin with a potent antipseudomonal action, was synthesized. In the study of the mode of action of this antibiotic in Escherichia coli, it was found that mutants which acquired resistance to E-0702 were isolated spontaneously and could be shown to be susceptible to its closely related derivatives, E-0702-060 and E-0702-061, and other representative beta-lactam antibiotics. In these mutants, no increased production of beta-lactamase was detectable. No apparent differences between the resistant mutants and the parental strains were observed in the affinity of E-0702 for penicillin-binding proteins. Furthermore, no significant reduction in or loss of both OmpF and OmpC porin proteins in the outer membrane was observed. The mutation was mapped to the tonB gene, which is known to be essential for the iron transport system of bacteria. The bactericidal action of E-0702 was rapidly expressed against iron-starved cells in which the iron transport system was induced, whereas the bactericidal action against iron-supplemented cells was ineffective. It is suggested that E-0702 is incorporated into bacterial cells as a chelator of iron via the tonB-dependent iron transport system, after which its strong and rapid bactericidal action is manifested.     

Low Direct Cytotoxicity and Cytoprotective Effects of Nitric Oxide Releasing Indomethacin

Nitric oxide (NO) releasing non-steroidal anti-inflammatory drugs (NSAIDs) have shown a marked reduction of gastrointestinal side effects and we here examined the cytotoxicity of NCX 530 (NO-indomethacin). Under conditions where indomethacin clearly induced both necrosis and apoptosis, NCX 530 induced neither. NCX 530 protected cells from celecoxib-induced necrosis and apoptosis. NCX 530 partially suppressed celecoxib-dependent membrane permeabilization and an inhibitor for guanylate cyclase suppressed the cytoprotective effect of NCX 530 against celecoxib. In vivo, NCX 530 alone produced fewer gastric lesions in rats than did indomethacin. A combination of the oral administration of celecoxib together with the intraperitoneal administration of indomethacin, but not of NCX 530, clearly resulted in the production of gastric lesions. The low direct cytotoxicity and the cytoprotective effect of NCX 530 observed in vitro may also act in vivo, thus ensuring that NCX 530 is safe for use on the gastric mucosa.     

Effects of Dobutamine Infusion on Mitral Regurgitation

Both intensity of mitral regurgitant murmur and color-coded Doppler regurgitant signal area have been reported to correlate with the degree of regurgitation. To evaluate the relationship between the intensity of regurgitant murmur and severity of mitral regurgitation, phonocardiography, echocardiography, and Doppler ultrasound were performed in 18 patients with mitral regurgitation before and during dobutamine infusion. Mitral regurgitation was due to mitral valve prolapse with ruptured chordae tendineae in 8 patients, rheumatic change in 5 patients, and dilated cardiomyopathy in 5 patients. With intravenous dobutamine infusion, heart rate (77–103 beats/min), systolic blood pressure (119–144 mmHg), peak mitral regurgitant jet velocity (4.5–5.4 m/sec), intensity of mitral regurgitant murmur (to 201% of that before infusion in early systole) increased, while left ventricular end-diastolic volume (124–102 mm), left ventricular end-systolic volume (57–42 mm), mitral anular diameter (33–28mm), and color Doppler mitral regurgitant signal area (704–416 mm²) decreased (P < 0.05). Total (forward + backward) left ventricular stroke volume (66–61 mL/beat) showed no change. Dobutamine decreased mitral regurgitant flow/beat, regardless of etiology of mitral regurgitation, which was probably due to the decrease of left ventricular size and mitral annular diameter. Although total (forward + backward) left ventricular stroke volume was unchanged, dobutamine effectively increased forward left ventricular stroke volume by decreasing backward regurgitation. Mitral regurgitant murmur became louder despite the decrease of mitral regurgation, indicating the uselessness of auscultation in the grading of the severity of mitral regurgitation.