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Pravastatin reduces restenosis after coronary angioplasty of high grade stenotic lesions: results of SHIPS (SHIga Pravastatin Study).

We conducted a multicenter prospective, randomized, double-blind, placebo-controlled trial to test whether pravastatin, a hydroxymethyl glutaryl coenzyme A reductase inhibitor, can decrease restenosis after percutaneous transluminal coronary angioplasty (PTCA). Pravastatin 10 mg twice daily was begun at least 10 days prior to elective PTCA in patients with total cholesterol less than 280 mg/dl. The end-point was a between-group comparison of the frequency of restenosis defined as a more than 50% loss of the initial gain in diameter stenosis at the PTCA site at 3 months during follow-up by automated quantitative coronary arteriography. Of 207 patients randomly assigned to study groups, 139 patients underwent PTCA; 133 procedures were successful, and 124 patients underwent follow-up angiography at 3 months, and 179 lesions (85 pravastatin, 94 placebo) in 124 patients (62 pravastatin, 62 placebo) were analyzed. The two groups were comparable for baseline characteristics. Total cholesterol decreased by 19.6% in the pravastatin group (p < 0.001) but not in the placebo group. Although the restenosis rate was not different in the two groups (29.4% in pravastatin vs. 39.4% in placebo, p = 0.215) as a whole, it was reduced to about one fifth (8.8%) in the pravastatin group compared with 44.8% in the placebo group (p = 0.0011) when the comparison was restricted to high grade lesions (> or = 75% diameter stenosis, 34 lesions in pravastatin, 29 lesions in placebo). Pravastatin thus reduces restenosis after PTCA of high grade lesions.

Adult↗

Usefulness of scintigraphic imaging using 131iodine-metaiodobenzylguanidine in localization of asymptomatic pheochromocytoma.

Localization of either multiple, metastatic and/or asymptomatic pheochromocytomas sometimes is elusive because all imaging methods to date have been nonspecific in character. We report 2 cases in which scintigraphy was used with a new radiopharmaceutical agent, 131iodine-metaiodobenzylguanidine, for the accurate localization of pheochromocytoma. To the best of our knowledge, this is the first report of asymptomatic pheochromocytoma imaged by 131iodine-metaiodobenzylguanidine scintigraphy.

3-Iodobenzylguanidine↗

Signature currents: a patch-clamp method for determining the selectivity of ion-channel blockers in isolated cardiac myocytes.

BACKGROUND: We describe a simple method using membrane potential ramps for rapidly determining the ion-channel selectivity of drugs that affect action-potential duration in isolated cardiac myocytes. The method allows the simultaneous assay of compounds on a number of ionic currents in a single cardiac cell. METHODS: Trains of membrane potential ramps were applied from -90 to +70 mV at 0.33 Hz to obtain a consistent "signature current," in which the major individual currents involved in the cardiac action potential could be easily identified. Confirmatory experiments were performed using known inhibitors of these currents. RESULTS: The identities of the currents in the signature were established by varying the concentrations of extracellular cations and by adding known ion channel blockers to superfusion solutions. Inhibition of each current had a characteristic and reproducible effect on the overall signature current. CONCLUSIONS: The consistent current signature in the presence and absence of blockers suggests that this method could be used for tertiary electrophysiological evaluation of compounds, eg, in a drug discovery program focusing on antiarrhythmic agents. The ability to assay for secondary effects of novel compounds against multiple currents in the target cell type is convenient and avoids the artefacts associated with using artificial expression systems.

Action Potentials↗

Utility of mixture of commercially available polymers as constituents of sustained-release microcapsules containing cefadroxil or theophylline.

Hydroxy propyl methyl cellulose acetate succinate high grade (AS-HG) and ethyl cellulose (EC) mixture microcapsules containing cefadroxil or theophylline were prepared by a solvent evaporation method in liquid paraffin dissolved sorbitan tri-stearate as a dispersing agent, and their sustained-release properties were evaluated. The microcapsules prepared with AS-HG:EC (in a 2:5 weight ratio) mixture containing 20% of cefadroxil or theophylline exhibited apparent zero-order releasing pattern in pH 6 to 8, at 50 rpm and 37 degrees C (paddle method). These microcapsules were administered orally to beagle dogs and the plasma concentrations of cefadroxil or theophylline were measured periodically. As a result of in vivo investigation, a satisfactory sustained-release plasma pattern and an apparent zero-order process in the gastrointestinal absorption were confirmed by deconvolution analysis of both drugs.

Administration, Oral↗

Relation between the instrumental activities of daily living and physical fitness tests in elderly women.

A cross-sectional study was conducted to quantitatively evaluate the relationship between the instrumental activities of daily living (IADL) and various physical fitness tests in elderly women living at home. The study focused on the total population of those women aged 65 years and over living in Y Town, Hyogo Prefecture, Japan, who visited a nursing home for day services. A total of 128 subjects were divided into two groups: dependent in IADL group (n = 49) and independent in IADL group (n = 79). The magnitude of the relation was evaluated by the odds ratio (OR). The following tests showed a significant decrease in IADL: knee-raising test [age-adjusted OR = 4.23, 95% confidence interval (CI) 1.81-9.87], height (age-adjusted OR = 4.09, 95% CI 1.75-9.56), grip strength (age-adjusted OR = 3.68, 95% CI 1.57-8.60), sit-and-reach test (age-adjusted OR = 2.76, 95% CI 1.20-6.34), and standing on one leg with closed eyes (age-adjusted OR = 2.56, 95% CI 1.09-5.97). Multivariate analysis using Hayashi's quantification method I indicated that knee-raising was the test most highly correlated with decreased IADL. These results suggest that measurement of knee-raising ability, muscle strength of the lower extremities and flexibility of hip joint could be the most useful factors to assess the level of instrumental self-support ability.

Activities of Daily Living↗

High efficiency gene transfer into murine T cell clones using a retroviral vector.

To establish a gene transfer and expression system for murine T cell clones, we have introduced the neomycin phosphotransferase gene encoding resistance to the neomycin analogue, G418, into non-neoplastic inducer T cell clones by using a replication-defective retroviral vector. This method allowed highly efficient gene transfer (20 to 40%) into two inducer T cell clones. The level of viral RNA expression in G418r T cells was 0.1% of poly(A)+ RNA. The infected G418r cells retained physiologic responsiveness to specific antigen as judged by antigen-specific proliferation and production of IL 3.

Animals↗

Anti-angiogenic activity of a novel synthetic agent, 9alpha-fluoromedroxyprogesterone acetate.

9Alpha-fluoromedroxyprogesterone acetate (FMPA) is a novel synthetic analog of medroxyprogesterone acetate (MPA), widely used as therapeutic agent for breast and endometrium cancers. FMPA showed almost the same binding affinities to the progesterone and glucocorticoid receptors as MPA. In the rabbit corneal assay, FMPA, MPA and fumagillin significantly inhibited the angiogenic response induced by rat mammary tumor at doses of 0. 1, 1 and 50 microg/pellet, respectively, so FMPA showed greater anti-angiogenic activity than MPA and fumagillin. In the mouse dorsal air sac method, FMPA inhibited the mouse sarcoma 180 cell-induced angiogenesis by oral administration at a dose of 200 mg/kg. FMPA inhibited the activity of plasminogen activator (PA) in bovine endothelial cells. These results suggest that FMPA may be useful for diseases associated with angiogenesis by oral administration.

Angiogenesis Inhibitors↗

Reconstruction of the cervical esophagus using a free transverse colonic graft: report of a case with upper esophageal web and carcinoma.

Reconstruction of cervical esophagus and hypopharynx following cervical esophagectomy and laryngopharyngectomy is generally performed using jejunal autograft interposition. However, this method has some disadvantages and is not suitable for optimal swallowing function. In our institution, free transverse colonic graft has been successfully applied for reconstructive purposes in 12 cases since 1986. The present report describes a case of upper esophageal web accompanying superficial squamous cell carcinoma and details the operative techniques utilized.

Aged↗

A novel mechanism of fluconazole resistance associated with fluconazole sequestration in Candida albicans isolates from a myelofibrosis patient.

A series of 10 strains of Candida albicans, from TIMM 3309 to TIMM 3318, were repeatedly isolated in one myelofibrosis-complicated patient with recurrent candidemia. The latter five isolates, from TIMM 3314 to TIMM 3318, became suddenly resistant to fluconazole during the 10 to 16 weeks after antimycotic therapy. We investigated the resistant mechanism of fluconazole using one susceptible isolate and two of the five resistant isolates in the series. The ergosterol synthesis by cell-free extracts from the two resistant isolates was less susceptible to fluconazole partly as a result of a decreased affinity of cytochrome P-450. Unexpectedly, these two resistant isolates showed higher levels of an intracellular accumulation of [H]fluconazole than the susceptible isolate and the control strain of C. albicans ATCC 10231. In the resistant isolate, TIMM 3318, most intracellular incorporated fluconazole was distributed in the 12,000 X g pellet (P-120) fraction by centrifugation unlike the two susceptible strains. An observation of the ultrastructure of TIMM 3318 showed the most notable alteration to be the characteristic appearance of numerous vesicular vacuoles (diameter, 150 to 400 nm); these vacuoles were not observed, however, in either of the susceptible strains. A direct observation of the subcellular fraction prepared from TIMM 3318 by the electron microscopy negative-staining method suggests that most of the vesicular vacuoles were recovered in the P-120 fraction. These results suggest that fluconazole sequestration caused by vesicular vacuoles of the resistant isolate might act as a novel mechanism of fluconazole resistance besides the decreased affinity of cytochrome P-450.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Preoperative localization of supernumerary and ectopic parathyroid glands in patients with secondary hyperparathyroidism].

The undetectable supernumerary and ectopic parathyroid glands have a high risk of persistent and recurrent hyperparathyroidism, especially in the patients with secondary hyperparathyroidism. Preoperative image diagnosis, CT scan, echogram and 201T1C1 scintigram were very useful for detecting supernumerary and ectopic parathyroid glands in our 132 patients who underwent parathyroidectomy for secondary hyperparathyroidism. Among these methods the scintigraphy showed the highest detection rate of the glands in the thymic tongue and in the upper mediastinum. CT scan showed the best detection rate of the glands located in the thyroid gland and those located between the thyroid gland and trachea. The echography was useful in detecting the glands in the thyroid gland, but could not offer easy visualization those located in the mediastinum. Even the ectopic parathyroid glands, weighing more than 500 mg were identifiable at about 90% when all the methods were applied routinely. In our experience, four patients had a supernumerary gland which was detected by the preoperative image diagnostic procedures at the initial surgery. One patient had a supernumerary gland in the mediastinum which was detected by image diagnosis after the initial operation and was removed at reoperation.

Adult↗

[A successful treatment of an infective endocarditis caused by methicillin-resistant Staphylococcus aureus with a combination of cefmetazole with fosfomycin].

A case of infective endocarditis caused by methicillin-resistant Staphylococcus aureus (MRSA) was successfully treated with a combination therapy with cefmetazole (CMZ) and fosfomycin (FOM). A 55 year old man was admitted to the Keio Hospital because of fever of unknown origin. Physical examination revealed blood pressure of 132/62 mmHg, heart rate of 118/min and body temperature of 39.8 degrees C. Diastolic regurgitant murmur (Levine II/VI) was heard at the left sternal border on the third intercostal space. Chest X-ray showed mild cardiomegaly. Two dimensional echocardiography and color flow mapping demonstrated mildly dilated and hyperkinetic left ventricle, redundant aortic valve, giant vegetation from the aortic valve and severe aortic regurgitation. MRSA was isolated from the blood of this patient. Bacteriostatic synergism between CMZ and FOM against S. aureus isolated from the blood of this patient was detected both by the Kirby-Bauer method and by the checker-board method. The combination therapy with CMZ and FOM cleared the clinical symptoms and normalized the inflammatory reactions. No relapse was observed for at least 10 months. We concluded that the combination therapy with CMZ and FOM was invaluable for the treatment of infections endocarditis by MRSA.

Cefmetazole↗

CT scan as a diagnostic tool to detect cancer invasion in the carotid artery.

The presence of cervical lymph node metastasis in head and neck tumors is usually determined by manual neck palpitation. However, this method cannot ascertain whether carotid artery invasion is present or not. Actually, fixed lymph node metastasis means nothing but deep fascia invasion of the metastasis. Contrast CT scan, on the contrary, can present exact information about the carotid artery. We investigate the comparison between CT scan results and surgical results in this paper.

Carotid Artery Diseases↗

Inheritance of Chediak-Higashi syndrome in Japanese black cattle.

Fifty-six Japanese black cattle affected with Chediak-Higashi syndrome (C-HS) have been referred to Miyazaki University Veterinary Teaching Hospital during the past 12 years, and 44 pedigree records were collected. In pedigree analysis, the parents had no clinical sign, the affected dams had clinically normal calves, and approximately equal numbers of males and females were affected, we therefore considered this syndrome to be an autosomal recessive trait. Quantitative genetic analyses were then made in a restricted area. Segregation analysis by the a priori method in 8 families showed that C-HS was a simple autosomal recessive trait. Furthermore, 36 dams and their 257 offspring (including 8 C-HS affected cattle) were analyzed using population genetics in the same area. The result was the same as in the former analysis.

Animals↗

Repetitive and safe transgene expression in rat liver is achievable by adenoviral infusion into the common bile duct.

To examine the feasibility of adenovirus-mediated gene transfer into the liver, we examined whether adenoviral infusion into the common bile duct could induce repetitive and safe transgene expression in rat livers. Recombinant adenovirus carrying a reporter lacZ gene was repetitively infused retrogradely into the common bile duct of rats. LacZ expression in rat livers was estimated histochemically by X-gal staining and quantitatively by a chemiluminescent reporter gene assay after the first, second and third adenoviral infusion into the common bile duct. To assess the safety of repetitive adenoviral infusion into the common bile duct, various liver- and kidney-related serum parameters, and liver damage were examined biochemically and histologically, respectively. Retrograde adenoviral infusion into the common bile duct achieved sufficient and safe lacZ expression in rat livers. Although transgene expression in the liver was transient, the second and third adenoviral infusion into the common bile duct could induce the expression of the same transgene in the liver. Furthermore, repetitive adenoviral infusion into the common bile duct caused no significant reverse reactions. Because retrograde adenoviral infusion into the common bile duct is a clinically practical method by using a widely used endoscopic technique, namely endoscopic retrograde cholangiography, these results suggest that retrograde adenoviral infusion into the common bile duct is a practical gene therapy modality in clinical settings.

Adenoviridae↗

Factors affecting visual outcomes after small-incision phacoemulsification in diabetic patients.

PURPOSE: To examine the factors affecting visual outcome after phacoemulsification and evaluate the use of preoperative visual potential in assessing the visual prognosis in diabetic patients. SETTING: Department of Ophthalmology, University of Texas Medical Branch, Galveston, Texas, USA. METHODS: In a retrospective chart review of 1345 consecutive patients who had uneventful small-incision phacoemulsification, operated eyes from 106 diabetic and 55 nondiabetic control patients were selected. Data on demographics, level of retinopathy, perioperative glycosylated hemoglobin (HbA(Ic)), surgical duration, preoperative best corrected visual acuity (BCVA), and visual potential were collected. RESULTS: The age, sex, preoperative BCVA, and visual potential in the diabetic and control eyes were comparable. Throughout the postoperative period, BCVA was worse of the diabetic group. At 1 year, BCVA was 20/40 in 82.1% of the diabetic group and 94.7% of the control group (P =.01). The most important factors affecting postoperative BCVA included coexisting diabetes and preoperative level of retinopathy. No correlation was found between perioperative and postoperative BCVA. Diabetic patients were less likely than control patients to achieve a BCVA better than or equal to the preoperative visual potential at 4 years (hazard ratio 0.6; 95% confidence interval, 0.4-0.9; P =.011). Patients with nonproliferative diabetic retinopathy were nearly 5 times less likely (P =.023) and patients with proliferative diabetic retinopathy 30 times less likely (P <.0001) to achieve a postoperative BCVA of 20/40 than diabetic patients without retinopathy. CONCLUSIONS: Although uneventful small-incision phacoemulsification improved visual acuity in diabetic patients, this group had an overall worse visual outcome than nondiabetic patients. The most important predictors of visual outcome were coexisting diabetes and the extent of preoperative retinopathy. Methods used to assess preoperative visual potential provided a reasonable estimate of postoperative BCVA in diabetic patients. Given the inverse association between the level of retinopathy and visual outcome, it may be better to perform cataract extraction in diabetic patients during earlier stages of retinopathy.

Adult↗

Evaluation of bitterness suppression of macrolide dry syrups by jellies.

The purpose of this study was to evaluate the bitterness-suppressing effect of three jellies, all commercially available on the Japanese market as swallowing aids, on two dry syrups containing the macrolides clarithromycin (CAM) or azithromycin (AZM). The bitterness intensities of mixtures of the dry syrups and acidic jellies were significantly greater than those of water suspensions of the dry syrups in human gustatory sensation tests. On the other hand, the mixture with a chocolate jelly, which has a neutral pH, was less bitter than water suspensions of the dry syrups. The bitterness intensities predicted by the taste sensor output values correlated well with the observed bitterness intensities in human gustatory sensation tests. When the concentrations of CAM and AZM in solutions extracted from physical mixtures of dry syrup and jelly were determined by HPLC, concentrations in the solutions extracted from mixtures with acidic jellies were higher than those from mixtures with a neutral jelly (almost 90 times higher for CAM, and almost 7-10 times higher for AZM). Thus, bitterness suppression is correlated with the pH of the jelly. Finally, a drug dissolution test for dry syrup with and without jelly was performed using the paddle method. There was no significance difference in dissolution profile. It was concluded the appropriate choice of jelly with the right pH is essential for taste masking. Suitable jellies might be used to improve patient compliance, especially in children. The taste sensor may be used to predict the bitterness-suppressing effect of the jelly.

Adult↗

Therapeutic effects of alendronate 35 mg once weekly and 5 mg once daily in Japanese patients with osteoporosis: a double-blind, randomized study.

The efficacy and safety of treatment with oral alendronate (ALN) 35 mg once weekly for 52 weeks were compared with those of ALN 5 mg once daily in a double-blind, randomized, multicenter study of Japanese patients with involutional osteoporosis. The primary efficacy end point was the percent change from baseline in the lumbar spine (L1-L4) bone mineral density (BMD) after 52 weeks of treatment. In this study, 328 patients were randomized to ALN 5 mg once daily (160 patients) or ALN 35 mg once weekly (168 patients). The adjusted mean percent change from baseline in lumbar spine (L1-L4) BMD after 52 weeks of treatment was 5.8% and 6.4% in the once-daily group and the once-weekly group, respectively (both P < 0.001). The 95% confidence interval for the difference in spine BMD change between the two treatment groups was -0.31% to 1.48%, indicating that the two regimens were therapeutically equivalent, since the confidence interval fell entirely within the predefined equivalence criterion (+/-1.5%). The time course of the spine BMD increase was also similar for both regimens. Regarding total hip BMD, mean changes from baseline at 52 weeks were 2.8% and 3.0% in the once-daily group and the once-weekly group, respectively. In addition, the bone markers (urinary deoxypyridinoline, urinary type-I collagen N-telopeptides, and serum bone-specific alkaline phosphatase) were reduced to a similar level by either treatment throughout the treatment period. The tolerability and safety profiles were also similar between the treatment groups. Taken together, we conclude that the efficacy and safety of the ALN 35-mg once-weekly regimen are therapeutically equivalent to those of the ALN 5-mg once-daily regimen.

Adult↗

Met-enkephalin-Arg6-Gly7-Leu8 in large-cored vesicles of splanchnic nerve terminals innervating guinea pig adrenal chromaffin cells.

Met-enkephalin-Arg6-Gly7-Leu8 (Met-Enk-Arg-Gly-Leu)-like immunoreactivity in the guinea pig adrenal medulla was investigated by the peroxidase-antiperoxidase method for light microscopy and by the protein A-gold method for electron microscopy. Because of a distinct Met-Enk-Arg-Gly-Leu-like immunoreactivity in the splanchnic nerve terminals innervating the chromaffin cell, their distribution and structure were clearly demonstrated. With electron microscopy, specific colloidal gold particles representing Met-Enk-Arg-Gly-Leu were localized in large-cored vesicles.

Adrenal Medulla↗