A comparative analysis of micafungin and caspofungin for empirical antifungal therapy in antibiotic-unresponsive febrile patients with hematologic malignancies.

This study was retrospectively carried out to compare the efficacy of echinocandins such as micafungin (MCFG) and caspofungin (CPFG) in the treatment of antibiotic-unresponsive febrile patients with hematologic malignancies. A total of 163 patients received either MCFG or CPFG. We evaluated the efficacy of echinocandin against fever decline in all patients. Fever decline, defined as a body temperature of less than 37.5 °C sustained for more than 48 h without scheduled antipyretic medication. Efficacy assessments showed that the incidence of fever decline was not significantly different between the MCFG and CPFG groups (P=0.599). The median number of days from the start of echinocandin administration to fever decline was 5 in both the MCFG and CPFG groups. Multivariate analysis showed that the use of anti-MRSA drugs (HR, 0.64; 95%CI, 0.45-0.90; P=0.011) and a change from echinocandins to voriconazole or liposomal-amphotericin B (HR, 0.50; 95%CI, 0.30-0.74; P<0.001) are significant risk factors for sustained fever. A significant difference (P=0.002) in incidence of fever decline was however associated with differences in the timing of anti-MRSA drug administration. The median number of days from the start of echinocandin administration to fever decline was 5 when administration of the anti-MRSA drug occurred "simultaneously or prior to echinocandin start" and 11 in the "next day or later of echinocandin start" group. In other words, starting anti-MRSA drug treatment after echinocandin treatment is a risk factor. In conclusion, MCFG and CPFG have similar efficacy as empirical antifungal agents in the treatment of antibioticunresponsive febrile patients with hematopoietic malignancies.

Economic evaluation of infection control activities.

BACKGROUND: Healthcare-associated infections by drug-resistant bacteria affect a patient's prognosis. Infection control activities at medical institutions in Japan are increasingly focused on the threat from these bacteria. AIM: To undertake a full cost analysis that included the costs of consumables and labour required for infection control activities. METHODS: The cost of infection control activities undertaken by the infection control team (ICT) at Nishimino Kosei Hospital in Japan was surveyed from January 2013 to December 2015. The evaluation index of infection control activities used the meticillin-resistant Staphylococcus aureus detection rate. The cost:effectiveness ratio (CER) of each intervention was calculated. FINDINGS: Consumables and labour costs increased over time, as did the ratio of labour cost to total cost over time. However, the CER of interventions was found to have decreased, from ¥164,177 in 2014 to ¥57,989 in 2015. There were increases not only in the amount of consumables, but also in ICT time, suggesting the possibility of improvements in the economic efficiency of infection control. CONCLUSION: Increasing the amount of consumables and the time input of the ICT could help improve the economic efficiency of infection control. Our research suggests the possibility for improvements in the economic efficiency of infection control.

Phosphorylation of CPI-17, an inhibitory phosphoprotein of smooth muscle myosin phosphatase, by Rho-kinase.

Phosphorylation of CPI-17 by Rho-associated kinase (Rho-kinase) and its effect on myosin phosphatase (MP) activity were investigated. CPI-17 was phosphorylated by Rho-kinase to 0.92 mol of P/mol of CPI-17 in vitro. The inhibitory phosphorylation site was Thr(38) (as reported previously) and was identified using a point mutant of CPI-17 and a phosphorylation state-specific antibody. Phosphorylation by Rho-kinase dramatically increased the inhibitory effect of CPI-17 on MP activity. Thus, CPI-17 as a substrate of Rho-kinase could be involved in the Ca(2+) sensitization of smooth muscle contraction as a downstream effector of Rho-kinase.

Hemodynamic study of ischemic limb by velocity measurement in foot.

By means of a tracer technique with 99mTc-pertechnetate, provided with seven zonal regions of interest, 6 mm in width, placed at equal spaces of 18 mm, from the toe tip to the midfoot at a right angle to the long axis of the foot, arterial flow velocity in the foot during reactive hyperemia was measured. The mean velocity in the foot was 5.66 +/- 1.78 cm/sec in 14 normal limbs, 1.58 +/- 1.07 cm/sec in 29 limbs with distal thromboangiitis obliterans (TAO), 0.89 +/- 0.61 cm/sec in 13 limbs with proximal TAO, and 0.97 +/- 0.85 cm/sec in 15 limbs with arteriosclerosis obliterans (ASO). The velocity returned to normal in all 12 limbs after successful arterial reconstruction, whereas the foot or toe blood pressure remained pathologic in 9 of the 12 limbs postoperatively; the velocity reverted to normal in 4 of 13 limbs after lumbar sympathectomy. When the velocity was normalized after operation, the ulceration healed favorably, and the ischemic limb was salvaged. The most characteristic feature of peripheral arterial occlusive disease of the lower extremity was a stagnation of arterial circulation in the foot, and the flow velocity in the foot was a sensitive predictive index of limb salvage.

Traumatic aneurysm of the abdominal aorta with acute thrombosis of bilateral iliac arteries.

A traumatic aneurysm of the abdominal aorta resulting in acute peripheral thrombosis is rare. A 29-year-old man suffered a sudden occlusion of the terminal abdominal aorta and bilateral iliac arteries. An infrarenal abdominal aortic aneurysm was found, along with destruction of lumbar vertebrae and an aberrant renal artery. The pathogenesis of this false aneurysm was thought to be traumatic rather than inflammatory because the patient's history and laboratory findings showed no signs of inflammatory reactions. He had been in an automobile accident five years previously, resulting in lumbar vertebral injury. Arterial reconstruction and intraoperative perfusion of the aberrant renal artery were performed successfully. To our knowledge, our case is the seventh one reported in the English literature of a traumatic aneurysm of the abdominal aorta successfully repaired by surgery.

Dynamics of iron-ascorbate-induced lipid peroxidation in charged and uncharged phospholipid vesicles.

Peroxidation of egg yolk phosphatidylcholine (egg PC) liposomes was induced by addition of ascorbic acid (AsA) and Fe(II) in the presence of a trace of autoxidized egg PC (PC-OOH), but not in the absence of PC-OOH. PC-OOH was degraded upon addition of AsA and Fe(II) but not of either one alone. The results suggest that PC-OOH is necessary to initiate lipid peroxidation by AsA/Fe(II). AsA oxidation in the bulk water phase was also associated with an increase in lipid peroxidation by AsA/Fe(II) in the presence of PC-OOH, but not in the absence of PC-OOH. Furthermore, the spin probe 12-NS [12-(N-oxyl-4,4'-dimethyloxazolidin-2-yl)stearic acid], which labels the hydrophobic region of dimyristoyl phosphatidylcholine (DMPC) liposomal membranes, was degraded upon addition of AsA and Fe(II) in the presence of PC-OOH, but not in the absence of PC-OOH. These results indicate that the "induction message" that is associated with decreases of PC-OOH and AsA in the initiation step of lipid peroxidation must be transferred from the membrane surface to the inner hydrophobic membrane region. AsA in the bulk phase was oxidized faster and more extensively upon its addition together with Fe(II) to egg PC liposomes than to DMPC liposomes, though the initial content of PC-OOH in the former was 5-10 times lower than in the latter. This suggests that, in egg PC liposomes, the OOH-groups of new PC-OOH generated in the inner membrane regions must become accessible from the surface, enabling reaction with AsA/Fe(II) which in turn would result in an extensive decrease in AsA.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of ilio-femoral venous occlusion.

During the past thirteen and a half years, 222 cases of iliofemoral venous occlusion were treated. Diagnosis was based mainly on clinical symptoms and phlebography. Surgery, injury, malignancy and heavy muscular exercise were the chief etiologic factors of this disease. As therapeutic maneuvres: (1) thrombectomy, (2) Palma's operation, (3) conservative procedures, (4) extirpation of a tumor, and (5) removal of secondary varicose veins were performed. Long-term results of treatment were reviewed. Thrombectomy and Palma's operation obtained good results in 59% and in 42% of cases respectively, while conservative procedures showed a favorable outcome in 36% of cases where followed. Results of thrombectomy were statistically better than those of conservative procedures (p less than 0.05).

Rhabdomyolysis and myocardial damage induced by palytoxin, a toxin of blue humphead parrotfish.

A 55-year-old man had rhabdomyolysis and myocardial damage induced by palytoxin. Weakness and myalgia of four extremities occurred five hours after eating a fish. Rhabdomyolysis developed and the serum creatine phosphokinase (CK) was elevated to 40,000 IU/l on the 3rd day. Gastric lavage with activated charcoal and forced mannitol-alkaline diuresis therapy were performed. The patient recovered with no complication such as renal failure. In this case, palytoxin was suggested to induce myocardial damage which was demonstrated by an elevation of the myosin light chain level and a change in electrocardiogram.

Pattern of arterial occlusion in Buerger's disease.

The pattern of arterial occlusion in Buerger's disease was analyzed by simultaneous bilateral femoral arteriography in 210 limbs of 105 patients with Buerger's disease. In 55 limbs of 42 patients, the femoropopliteal segment was affected in addition to the infrapopliteal arterial obstructive lesion. The pattern of crural arterial occlusion was similar in about 40% of both the patients with femoropopliteal occlusion and the patients with crural occlusion. Toes were ulcerated in 4 of 58 limbs with continuous arterial flow, and ulceration occurred in 86 of 152 limbs with a discontinuous flow. The rate of occurrence of bilateral trophic lesion in the group with an arteriographically similar occlusion pattern was not significantly higher than that in the group with a different pattern. The pattern of arterial occlusion in Buerger's disease seemed to be fixed mainly within 1 year after the onset of symptoms, and the skip-lesion in the main artery was favorable to proximal progression of the disease.

Measurement of blood pressure in all toes in arterial occlusive disease of the leg.

In the present study, systolic blood pressure in all toes was measured by using a bladder-free cuff in 20 normal limbs and 106 limbs with arterial occlusive disease, and the clinical significance of blood pressure measurement in all toes was studied. In 97 of 106 limbs with arterial occlusion, all 5 toes showed a significantly decreased blood pressure, indicating that any toe can be used for the purpose of diagnosis of arterial occlusions. However, 41% of cases showed the difference in blood pressure of more than 15 mm Hg between any 2 toes. Great variations of blood pressure among 5 toes were observed especially in limbs with gangrene or with other skin ischemic symptoms such as cold sensitivity, numbness, or history of gangrene in the toes. In these cases, evaluation of hemodynamics in each toe is considered to be of use for prognostic study of gangrene, selection and evaluation of treatments, and follow-up study. In limbs with intermittent claudication, however, blood pressure measurement in all toes may have little value in clinical practice because of small variation among blood pressure values of 5 toes. In comparison of blood pressure values in each toe from limbs with gangrene, toes with gangrene showed a significantly lower blood pressure than toes without gangrene. However, even in these toes without gangrene, a significantly lower blood pressure was observed than in toes from limbs without gangrene. These findings indicate that severe damage to digital circulation due to an occlusive process proximal to the toes is a primarily indispensable condition for development of gangrene in arterial occlusive disease.

A case of superficial spreading melanoma in situ 2.5 mm in diameter.

A 60-year-old woman with superficial spreading melanoma in situ, measuring 2.5 mm in diameter, was examined. She had noticed a very small pigmented lesion 1.2 mm in diameter on her left lower leg in April of 1989. By April of 1990, it had grown to 2.5 mm in diameter. Its edge was irregular, and its color was variegated black to brown. Skin surface markings had disappeared in the center portion. Histopathologically, the lesion was asymmetrical. Atypical large cells nested in the lower epidermis and were scattered singly in the mid and upper epidermis, as seen in Paget's disease. At the periphery of the lesion, single large tumor cells were scattered in the mid epidermis. The tumor cells reacted to monoclonal anti-melanoma antibody HMB-45.

Measurement of blood pressure, blood flow and flow velocity in arterial reconstruction of the lower extremity.

Seventy-five limbs of 66 patients undergoing arterial reconstruction of the lower extremity were studied. In 41 of 64 limbs that were not involved in early failure, API returned to normal immediately and the increased API was maintained as long as grafts remained patent. The limbs exhibiting a rise in API of 0.1 or more following proximal reconstruction in the cases with combined iliac and femoral arterial occlusion or bypass grafting to an isolated segment obtained marked improvement of symptoms. Postoperative increase in TPI was not so marked as in API, and TPI remained very low in the limbs with arterial obstructive lesions below the ankle after successful reconstruction. Early or late failure could not be predicted on the basis of preoperative or postoperative API, TPI or A-T gradient. In the limbs with no recovery of TPI, blood flow or flow velocity in the foot was of value predicting which limbs would be salvaged.

Indirect blood pressure measurement at the common femoral artery.

In the present study the technique and the reliability of indirect blood pressure measurement at the common femoral level was described. The blood pressure was measured by using a long cuff, which encircled the hips at the level of the groin, and determining the flow signals by Doppler technique applied at the ankle. In order to transmit the cuff pressure to the artery, a slender bag with air, which was a blood pressure cuff used in children, was placed over the common femoral artery under the cuff. A 14 cm. wide cuff-bladder was usually used, but in obese subjects with the size of hips more than 90 cm, a 16 cm. wide cuff-bladder was applied. In patients with collateral vessels around the groin due to the iliac disease, the blood pressure could be measured by placing the Doppler flat probe over the common femoral artery or the collateral vessel. In observation of 24 subjects, a close correlation was obtained between the femoral cuff pressures and common femoral intra-arterial pressures. Furthermore, blood pressure values at the common femoral level measured indirectly showed similar reproducibility as those at the ankle and toe levels.

Arterio-venous fistula formation after hand replantation.

Replantation of a completely severed finger, hand or arm is now performed with wide success. We now report an extremely rare complication of this replantation, an arterio-venous (A-V) shunt formation. Pathogenesis of the new A-V fistula formation is discussed.

Structure-activity study and analgesic efficacy of amino acid derivatives as N-type calcium channel blockers.

The synthesis and structure-activity relationship (SAR) study of a novel series of N-type calcium channel blockers are described. L-Cysteine derivative 2a was found to be a potent and selective N-type calcium channel blocker with IC(50) 0.63 microM on IMR-32 assay. Compound 2a showed analgesic efficacy in the rat formalin-induced pain model by intrathecal and oral administration.

Phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by protein kinase N.

CPI-17 is a phosphorylation-dependent inhibitory protein for smooth muscle myosin phosphate. Phosphorylation at Thr(38), in vitro, by protein kinase C or Rho-kinase enhances the inhibitory potency toward myosin phosphatase. Phosphorylation of CPI-17 by protein kinase N (PKN), a fatty acid- and Rho-activated serine/threonine kinase, and its effect on smooth muscle myosin phosphatase activity were investigated. CPI-17 was phosphorylated by GST-PKN-CAT, a constitutively active GST-fusion fragment of PKN, to 1.46 mol of P/mol of CPI-17, in vitro. The K(m) value of CPI-17 for PKN was 0.96 microM. Phosphorylation of PKN dramatically increased the inhibitory effect of CPI-17 on myosin phosphatase activity. The major and inhibitory phosphorylation site was identified as Thr(38) using a point mutant of CPI-17 and a phosphorylation-state specific antibody. Thus, CPI-17 is a substrate of PKN and might be involved in the Ca(2+) sensitization of smooth muscle contraction as a downstream effector of Rho and/or arachidonic acid.

Purification and characterization of rhesus monkey liver amido hydrolases and their roles in the metabolic polymorphism for E6123, a platelet-activating factor receptor antagonist.

We previously showed that a polymorphism for E6123 [(S)-(+)-6- (2-chlorophenyl)-3-cyclopropanecarbonyl-8,11-dimethyl-2,3,4,5- tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a] [1,4]diazepine] metabolism exists only in rhesus monkeys. In the present study, we purified, from rhesus monkey hepatic microsomes, three amido hydrolases that are involved in the metabolic polymorphism. Two forms of amido hydrolase from an extensive metabolizer and one from a poor metabolizer were purified by Q-Sepharose Fast Flow, Red A-agarose, octylamino-Sepharose 4B, and hydroxyapatite-Ultrogel chromatography, after solubilization with Lubrol. The three purified enzymes had the same molecular mass (47 kDa), and their amino-terminal amino acid sequences were identical. The enzymes were different from various known carboxylesterases in terms of substrate specificity, molecular mass, and amino-terminal amino acid sequence. They resembled arylacetamide deacetylase from human hepatic microsomes with respect to molecular mass and amino-terminal amino acid sequence. The KM values of the high and low affinity enzymes in the extensive metabolizer and the sole enzyme in the poor metabolizer were 37.6, 73.0, and 76.5 microM, respectively. The Vmax values were 3312.4, 504.8, and 427.9 pmol/min/mg of protein, respectively. The high affinity enzyme in extensive metabolizer appears to be quite distinct, whereas the low affinity enzyme in extensive metabolizer in similar or identical to the sole enzyme in poor metabolizer. Thus, the metabolic polymorphism in rhesus monkey may depend upon the existence of the high affinity enzyme in extensive metabolizer.

Predictive value of remnant-like particles cholesterol/high-density lipoprotein cholesterol ratio as a new indicator of coronary artery disease.

BACKGROUND: There is as yet no definite consensus on the predictive value of the various lipid profiles and fibrinolytic parameters that became available in clinical use recently for coronary artery disease. METHODS: Levels of lipoprotein(a), high-density lipoprotein cholesterol (HDL-C), remnant-like particles cholesterol (RLP-C), tissue plasminogen activator (TPA), TPA inhibitor, antithrombin III, and protein C were measured in 124 patients who underwent diagnostic coronary angiograms. RESULTS: Of these patients, 37 had no significant stenoses (group N) and 87 had significant stenoses (group S). There were no significant differences in patient characteristics between the two groups. HDL-C was significantly lower (p = 0.0071 ) and RLP-C was significantly higher (p = 0.0022) in group S. When a product and a ratio of each of two factors were calculated, RLP-C/HDL-C was demonstrated to be a highly significant predictor for coronary artery stenoses (p < 0.0001). There were also significant increases in RLP-C/HDL-C levels with increasing number of vessels involved (r = 0.359, p < 0.0001 ). CONCLUSION: Our present study disclosed the predictive value of RLP-C/HDL-C ratio as a new indicator of coronary artery disease.