What is the evidence status of Appropriate Use Criteria (AUC)? Insight from a matching exercise with the guidelines for echocardiography.

There is interest in adapting the American Appropriate Use Criteria (AUC) for transthoracic echocardiography to Australian practice. We matched 90 of 98 AUC with the guidelines (53 appropriate, 12 sometimes appropriate, 25 rarely appropriate), but eight lacked any match. Among the matched criteria, 76 (82%) indications were concordant with the guidelines. A stronger evidence base would be desirable to settle these discrepancies before Australian adoption of AUC.

Comparative study of treatment efficacy and the incidence of post-inflammatory hyperpigmentation with different degrees of irradiation using two different quality-switched lasers for removing solar lentigines on Asian skin.

BACKGROUND: Quality-switched (QS) lasers are well-known effective treatment for removing solar lentigines. However, the high incidence of post-inflammatory hyperpigmentation (PIH) raises concern in darker skin types. This is the first study comparing efficacies and incidences of PIH in Asian skin with different degrees of irradiation between two QS lasers. METHOD: In total, 355 solar lentigines in 193 cases, skin types III-V, were randomly divided into four groups. All cases received single laser treatment. Clinical results were evaluated after 4 weeks. Groups 1 and 3 were treated 'aggressively' with endpoints of very obvious immediate whitening (IW) of the lesion. Groups 2 and 4 were treated 'mildly' with endpoints of slight IW of the lesion. Groups 1 and 2 were irradiated with the QS ruby, and groups 3 and 4 with the QS frequency doubled Nd:YAG laser. RESULTS: There were no statistically significant differences in degrees of clearance among the four groups. However, PIH incidences were very different: 33.33%, 7.47%, 23.18% and 8.47% in groups 1, 2, 3 and 4 respectively. The difference between aggressively and mildly irradiated groups (1 and 3 vs. 2 and 4) was statistically significant (P < 0.001). However, there was no statistical difference between the two aggressively or the two mildly irradiated groups. There were no significant differences between skin types. CONCLUSION: Aggressive irradiation using QS lasers resulted in a high PIH incidence, while having no advantage in efficacy. For darker skin types, mild irradiation reduces the PIH risk with no disadvantage in efficacy.

Renal L-type fatty acid-binding protein mediates the bezafibrate reduction of cisplatin-induced acute kidney injury.

Fibrates, the PPAR alpha ligand-like compounds increase the expression of proximal tubule liver fatty acid binding protein (L-FABP) and significantly decrease cisplatin-induced acute kidney injury. To study whether the bezafibrate-mediated upregulation of renal L-FABP was involved in this cytoprotective effect we treated transgenic mice of PPAR agonists inducible human L-FABP expression with cisplatin in the presence or absence of bezafibrate. Blood urea nitrogen was unchanged in the first day but increased 3 days after cisplatin. While urinary L-FABP increased over 100-fold 1 day after cisplatin treatment in the transgenic mice it was significantly reduced when these transgenic mice were pretreated with bezafibrate. Cisplatin-induced renal necrosis and apoptosis were significantly reduced in bezafibrate pretreated transgenic mice and this correlated with decreased accumulation of lipid and lipid peroxidation products. Immunohistochemical analysis of kidney tissue of bezafibrate-cisplatin-treated transgenic mice showed preservation of cytoplasmic L-FABP in the proximal tubule, but this was reduced in transgenic mice treated only with cisplatin. L-FABP mRNA and protein levels were significantly increased in bezafibrate-cisplatin-treated transgenic mice when compared to mice not fibrate treated. Our study shows that the bezafibrate-mediated upregulation of proximal tubule L-FABP plays a pivotal role in the reduction of cisplatin-induced acute kidney injury.

Arachidonic acid and docosahexaenoic acid supplementation increases coronary flow velocity reserve in Japanese elderly individuals.

BACKGROUND: Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important components of phospholipids and cell membranes. There has, however, been no clinical report on the direct effects of ARA and DHA on coronary circulation. OBJECTIVE: To evaluate the effects of ARA and DHA on coronary circulation using the measurement of coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography (TTDE). METHODS: A double-blind, placebo-matched study of 28 Japanese elderly individuals (19 men, mean age 65 years) conducted to compare the effects of polyunsaturated fatty acids (PUFA; ARA 240 mg/day, DHA 240 mg/day) and placebo on CFVR. Coronary flow velocity (CFV) of the left anterior descending coronary artery was measured at rest and during hyperaemia by TTDE to determine CFVR. RESULTS: There were no significant differences in CFV at rest or during hyperaemia in CFVR at baseline in the two groups (PUFA versus placebo 17 (7 SD) versus 16 (6), 62 (20) versus 59 (12), and 3.85 (1.04) versus 3.98 (0.83) cm/s, respectively). After three months' supplementation, CFV during hyperaemia was significantly higher in the PUFA than in the placebo group (73 (19) versus 64 (12) cm/s, p<0.01) although no significant difference was found between the two groups in CFV at rest (17 (7) versus 16 (4) cm/s). CFVR thus significantly increased after PUFA consumption (3.85 (1.04) versus 4.46 (0.95), p = 0.0023). CONCLUSION: Three months' supplementation of PUFA increased CFVR in Japanese elderly individuals, which suggests beneficial effects of PUFA on the coronary microcirculation.

A role of liver fatty acid-binding protein in cisplatin-induced acute renal failure.

Previous studies from our laboratory showed that increased fatty acid oxidation by the kidney is cytoprotective during cisplatin (CP)-mediated nephrotoxicity. In this study, we determined the effects of CP and fibrates on peroxisome proliferation and the expression of liver fatty acid-binding protein (L-FABP) in normal mice, and in mice transgenically overexpressing human L-FABP (h-L-FABP). Labeling of peroxisomes demonstrated reduced peroxisomal staining in the proximal tubule of CP-treated mice compared with control mice. There was increased peroxisomal labeling in the proximal tubules of both control and CP-treated mice when either was treated with fibrate; a known peroxisome proliferator-activated receptor-alpha ligand. L-FABP protein expression, not detected in control or CP-treated mice, was significantly increased in the proximal tubules of fibrate-treated mice of either group. In the transgenic mice, CP increased the shedding of h-L-FABP in the urine, which was decreased by fibrate as was the acute renal failure. A cytosolic pattern of h-L-FABP expression was found in the proximal tubules of untreated transgenic mice with a nuclear presence in CP-treated mice. Fibrate pretreatment restored the cytosolic expression pattern in CP-treated mice. Our study shows that fibrate may improve CP-induced acute renal failure due to both peroxisome proliferation and increased L-FABP in the cytosol of the proximal tubule.

Supplement nephropathy due to long-term, high-dose ingestion of ascorbic acid, calcium lactate, vitamin D and laxatives.

A 48-year-old Japanese woman previously in good health was found to have severe proximal tubular dysfunction with a high serum level of ascorbic acid (57.3 microg/ml, reference range: 1.9 - 15.0 microg/ml). Renal biopsy specimen showed marked tubulointerstitial damage, i.e. tubular atrophy, dilatation of tubular lumen with flattened tubular epithelial cells, vacuolization of proximal and distal tubular epithelial cells, and severe interstitial fibrosis with mild infiltration of mononuclear cells. Calcified lesions, which caused tubular obstruction or stenosis, were also seen in interstitial area adjacent to degenerated proximal tubuli. Hypokalemic nephropathy, probably due to long-term use of laxatives, was clearly shown. However, calcified lesions seemed to be caused by inappropriate excessive daily ingestion of ascorbic acid (6 000 mg/day), calcium lactate, and vitamin D because of the patient's misunderstanding that these supplements could keep her in a good health. This condition may be clinically called "supplement nephropathy".

Diabetic ketoacidosis in a case of pheochromocytoma.

A 31-year-old woman was admitted to our hospital because of diabetic ketoacidosis (DKA). Ultrasound sonography revealed the existence of the left adrenal tumor and endocrinological examinations established a diagnosis of pheochromocytoma. She had been healthy and there was no evidence for gestational diabetes in her personal history. Characteristic features were not found in her tumor size and the catecholamine levels as compared with typical cases of pheochromocytoma. An overwhelming secretion of catecholamine might suppress insulin secretion, as evidenced by the improvement after the resection of the tumor. However, a significant insulin resistance continued after tumor resection. Obesity and the heterozygosity of beta3-adrenergic receptor gene (Try64Arg) might play a role in insulin resistance, which resulted in DKA at least in part. Literature survey revealed four cases of DKA in the patients with pheochromocytoma including ours, three of which were Japanese. Pancreatic capacity to secrete insulin has been reported to be less than Caucasians, which might be another reason for DKA. Thus, we speculate that both suppressed insulin secretion and insulin resistance deteriorated by obesity or other factor(s) such as abnormality in beta3 adrenergic receptor probably depress beta-cell function resulting in abnormal metabolic imbalance such as DKA.

Highly efficient random mutagenesis in transcription-reverse-transcription cycles by a hydrogen bond ambivalent nucleoside 5'-triphosphate analogue: potential candidates for a selective anti-retroviral therapy.

The nucleoside P can base pair with both A and G. We evaluated the mutation frequency induced by the 5'-triphospbate of the ribonucleoside P (PTP) in an in vitro retroviral replication model. After 4 cycles of replication in the presence of PTP, the mutation frequency was raised to 3.8 x 10(-2) per nucleotide and C-to-U and U-to-C mutations were dominantly observed. These results suggest that ambivalent NTP analogues, like PTP, could induce mutations beyond the error threshold of retroviruses.

Inhibition of DNA adduct formation and mutagenic action of 3-amino-1-methyl-5h-pyrido[4,3-b]indole by chlorophyllin-chitosan in rpsL transgenic mice.

We have studied the inhibitory effect of chlorophyllin-chitosan (Chl-Chi) complex, an insoluble form of chlorophyllin, on the DNA adduct formation and mutagenesis by a heterocyclic food mutagen-carcinogen, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), in mice carrying the E. coli rpsL gene as a mutagenesis reporter. Upon administration of a diet containing 0.002% or 0.01% Trp-P-2, DNA adducts were formed in various tissues in a dose-dependent manner, with the maximum level observed in the liver. Addition of 3% Chl-Chi to the diet reduced the Trp-P-2 adduct by up to 90%. The rpsL mutant frequencies increased significantly in both the liver and spleen upon administration of a 0.01% Trp-P-2 diet. Addition of Chl-Chi to the diet decreased these induced mutant frequencies to the background level. No harmful effect of Chl-Chi was detected during these experiments. The results show that Chl-Chi may be a candidate chemopreventive agent against the genotoxic action of Trp-P-2, and possibly also other aromatic carcinogens in the diet.

Effect of chromatic aberration on contrast sensitivity in pseudophakic eyes.

OBJECTIVE: To evaluate the effect of chromatic aberrations in pseudophakic eyes with various types of intraocular lenses (IOLs). PATIENTS AND METHODS: The study included 51 eyes of 33 patients who underwent cataract surgery. The eyes were divided into 3 groups according to the material from which their IOL was made: group 1, polymethyl methacrylate; group 2, silicone; and group 3, an acrylate/methacrylate copolymer. Ten normal phakic control eyes (group 4) underwent the same examination. Best-corrected distance visual acuity and contrast sensitivity were measured under white light and monochromatic light with wavelengths of 470 nm, 549 nm, and 630 nm, with the best correction under white light. RESULTS: There were no significant differences in best-corrected visual acuity and contrast sensitivity under the 549-nm monochromatic light in any group. However, under both white multichromatic light and 470- and 630-nm monochromatic light, the mean contrast sensitivity in group 3 tended to be lower, sometimes significantly, than in the other IOL groups. CONCLUSIONS: Our results showed that longitudinal chromatic aberrations of some IOLs may degrade the quality of the retinal image. Attention must be paid to the detailed optical performance of IOL materials to achieve good visual function.

Photorejuvenation for Asian skin by intense pulsed light.

BACKGROUND: Dermabrasion and deep chemical peeling are used in the treatment of photoaged skin. These ablative procedures are effective enough to produce a certain improvement but have often caused postinflammatory hyperpigmentation among Asian patients. To avoid such adverse effects, a new, nonablative procedure has been sought. OBJECTIVE: To determine the effectiveness of photorejuvenation for Asian skin using intense pulsed light (IPL). The specific parameters used, improvement ratios, side-effects, and downtime required are also discussed. METHODS: Ninety-seven patients were treated for photoaging using IPL. The cutoff filters of 550 nm and 570 nm were utilized for three to six treatments at intervals of 2 to 3 weeks. RESULTS: Treatment results were evaluated and rated by both patients and physicians at the end of the third treatment based on improvement in pigmentation, telangiectasia, and skin texture. A combined rating of "good" or "excellent" was given to more than 90% of the patients for pigmentation, more than 83% for telangiectasia, and more than 65% for skin texture. There were some minor complications in four cases: one had erythema that continued to the next day and three had minor blisters leaving no marks. CONCLUSION: Photorejuvenation using IPL is a completely safe and effective procedure even for Asian skin. It will be increasingly used for skin rejuvenation in the future.

Binding specificities of the mismatch binding protein, MutS, to oligonucleotides containing modified bases.

We have studied the effects of DNA mismatch repair on mutagenesis induced by nucleoside analogs. Among them, the mutagenic action of 3,4-dihydro-6H,8H-pyrimido[4,5-c][1,2]oxazin-7-one 2'-deoxyriboside (dP) showed high susceptibility to the mismatch repair system, while mutagenesis by N4-aminocytidine and N4-hydroxycytidine was only weakly affected. 2-Aminopurine mutagenesis showed intermediate susceptibility. MutS protein specifically bound to an oligonucleotide duplex containing a dP-dG pair, while the dP-dA pair was bound only weakly. The binding to the dP-dG pair was as strong as binding to a dA-dC mismatch. These specific binding properties can explain the effective avoidance of dP-induced mutagenesis by the mismatch repair system. We have also studied the effects of the repair system on mutagenesis induced by methylating and ethylating agents.

Reverse transcriptional mutagenesis induced by ribonucleoside triphosphate analogue, PTP and its availability for anti-HIV-1 therapy.

The bicyclic pyrimidine analogue, 3,4-dihydro-6H,8H-pyrimido[4,5-c][1,2]oxazin-7-one (P) can base pair with both A and G. The riboside 5'-triphsophate of P (PTP) efficiently induces mutation during in vitro transcription and reverse transcription cycles using a phage promoter. In the present study, we have constructed an in vitro transcription system promoted by the human immunodeficiency virus type 1 (HIV-1) 5'-long terminal repeat (LTR) using HeLa nuclear extract supplemented with HIV-1 Tat protein. Using this system, the effects of mutagenic ribonucleotide analogues were studied.

Defining a neural network controller structure for a rubbertuator robot.

Rubbertuator (Rubber-Actuator) robot arm is a pneumatic robot, unique with its lightweight, high power, compliant and spark free nature. Compressibility of air in the actuator tubes and the elastic nature of the rubber, however, are the two major sources of increased non-linearity and complexity in motion control. Soft computing, exploiting the tolerance of uncertainty and vagueness in cognitive reasoning has been offering easy to handle, robust, and low-priced solutions to several non-linear industrial applications. Nonetheless, the black-box approach in these systems results in application specific architectures with some important design parameters left for fine tuning (i.e. number of nodes in a neural network). In this study we propose a more systematic method in defining the structure of a soft computing technique, namely the backpropagation neural network, when used as a controller for rubbertuator robot systems. The structure of the neural network is based on the physical model of the robot, while the neural network itself is trained to learn the trajectory independent parameters of the model that are essential for defining the robot dynamics. The proposed system performance was compared with a well-tuned PID controller and shown to be more accurate in trajectory control for rubbertuator robots.

Insulin levels during fasting and the glucose tolerance test and Homa's index predict subsequent development of hypertension.

OBJECTIVE: To determine whether there is a longitudinal relationship between hypertension and hyperinsulinemia and to find the most useful parameter(s) for predicting the subsequent development of hypertension. SUBJECTS AND METHODS: The oral glucose (75 g) tolerance test (OGTT) was performed in 313 patients, who were divided into three groups according to glucose tolerance based on the WHO criteria: normal, borderline and diabetes mellitus. The fasting insulin (IRI) levels, sigmaIRI (the sum of the insulin levels 0, 30, 60 and 120 min after the OGTT), insulinogenic index and Homa's index, a candidate for the simple assessment of insulin sensitivity, of the normotensive and hypertensive subjects in each subgroup were compared. In addition, 145 normotensive subjects were followed up for over 3 years and observed for the development of hypertension. RESULTS: Hypertensive diabetic subjects had not only higher fasting IRI levels and sigmaIRI values, but they also had higher Homa's indices than normotensive diabetics. Normotensive subjects with normal glucose tolerance (n = 20) did not develop hypertension. However, 16 out of 94 patients with borderline glucose tolerance and five out of 31 diabetics became hypertensive. The incidence of hypertension in the group with fasting IRI > or = 15, sigmaIRI > or = 150 or Homa's index > or = 4 was between 5 and 9 times higher than that in the group with fasting IRI < 10, sigmaIRI < 100 or Homa's index < 2. This difference was still significant when multivariate analysis, including various factors such as age, body mass index (BMI) and sex, was performed. CONCLUSIONS: These results suggest that higher plasma IRI levels and/or insulin resistance are closely related to the pathogenesis of hypertension in patients with diabetes mellitus. Homa's index, fasting and sigmaIRI may be useful predictors of the subsequent development of hypertension.

Retrovirus-specific random mutagenesis by a nucleoside 5'-triphosphate analogue, PTP.

In a retrovirus replication model system, which consists of in vitro transcription and reverse transcription cycles, 6-(beta-D-ribofuranosyl)-3,4- dihydro-8H-pyrimido[4,5-c][1,2]oxazin-7-one-5'-triphosphate (PTP) induced highly efficient random mutations and this was due to the ambiguous incorporation of PTP by RNA polymerases. The types of mutations were mainly C-to-U or U-to-C transition mutations and the frequency was about 4 x 10(-2)/nucleotide during four cycles of the replication. Since a high mutation rate is harmful to species, PTP may be new candidate for anti-retroviral drugs. N4-aminoCTP and N4-hydroxyCTP were also incorporated ambiguously by RNA polymerase. These compounds may have a potential to induce mutation by the same mechanism as PTP.