Effect of photodynamic therapy with 5-aminolevulinic acid and EDTA-2Na against mixed infection of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

BACKGROUND: The increasing abundance of drug-resistant bacteria is a global threat. Photodynamic therapy is an entirely new, non-invasive method for treating infections caused by antibiotic-resistant strains. We previously described the bactericidal effect of photodynamic therapy on infections caused by a single type of bacterium. We showed that gram-positive and gram-negative bacteria could be killed with 5-aminolevulic acid and 410 nm light, respectively. However, clinically, mixed infections are common and difficult to treat. OBJECTIVE: We investigated the bactericidal effects of photodynamic therapy on mixed infections of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. METHODS: We compared bacterial growth with and without photodynamic therapy in vitro. Then, in vivo, we studied mixed infections in a mouse skin ulcer model. We evaluated the rates of ulcer area reduction and transitions to healing in treated and untreated mice. In addition, a comparison was made between PDT and existing topical drugs. RESULTS: We found that photodynamic therapy markedly reduced the growth of both methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, in culture, and it reduced the skin ulcer areas in mice. PDT was also more effective than existing topical medicines. CONCLUSION: This study showed that photodynamic therapy had antibacterial effects against a mixed infection of gram-positive and gram-negative bacteria, and it promoted skin ulcer healing. These results suggested that photodynamic therapy could be effective in both single- and mixed-bacterial infections.

Open study of photodynamic therapy for skin ulcers infected with MRSA and Pseudomonas aeruginosa.

BACKGROUND: Drug-resistant bacterial infections are a global problem. Novel treatment methods that simultaneously control infection and promote wound healing without leading to new resistant bacteria are needed. Photodynamic therapy (PDT) is a useful antibiotic-free treatment approach. Our previous studies have shown that PDT for skin ulcers infected with methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA) can achieve infection control and promoting wound healing in vitro and in vivo murine model. Here, we investigated the safety and effectiveness of PDT with 5-aminolevulinic acid (ALA-PDT) for human skin ulcers infected with MRSA and PA. METHODS: ALA-PDT with macrogol ointment containing 0.5% ALA-HCl and 0.005% EDTA-2Na (wavelength 410 nm, 10 J/cm2) was performed on consecutive days in patients aged ≥20 years who had skin ulcers infected with MRSA and PA. RESULTS: Six of our seven patients showed a clear tendency for ulcer area reduction to ≤60% of that measured at baseline. ALA-PDT was judged to be completely safe in all patients; only one patient had an increase in bacterial count. CONCLUSIONS: ALA-PDT is safe and effective for MRSA and PA infected skin ulcers to control and heal wound.

Incident Fluence Analysis for 755-nm Picosecond Laser Treatment of Pigmented Skin Lesions Based on Threshold Fluences for Melanosome Disruption.

BACKGROUND AND OBJECTIVES: In this study, the threshold fluences for disrupting the melanosomes for pigmented skin lesion treatment were determined using a 755-nm picosecond laser for clinical use. Based on the melanosome disruption thresholds, incident fluences corresponding to the target lesion depths were evaluated in silico for different laser spot sizes. STUDY DESIGN/MATERIALS AND METHODS: Melanosome samples were isolated from porcine eyes as alternative samples for human cutaneous melanosomes. The isolated melanosomes were exposed to 755-nm picosecond laser pulses to measure the mean particle sizes by dynamic light scattering and confirm their disruption by scanning electron microscopy. The threshold fluences were statistically determined from the relationships between the irradiated fluences and the mean particle sizes. Incident fluences of picosecond laser pulses for the disruption of melanosomes located at different depths in skin tissue were calculated through a light transport simulation using the obtained thresholds. RESULTS: The threshold fluences of 550- and 750-picosecond laser pulses were determined to be 2.19 and 2.49 J/cm2 , respectively. The numerical simulation indicated that appropriate incident fluences of picosecond laser pulses differ depending on the depth distribution of the melanosomes in the skin tissue, and large spot sizes are desirable for disrupting the melanosomes more deeply located within the skin tissue. CONCLUSION: The threshold fluences of picosecond laser pulses for melanosome disruption were determined. The incident fluence analysis based on the thresholds for melanosome disruption provides valuable information for the selection of irradiation endpoints for picosecond laser treatment of pigmented skin lesions. Lasers Surg. Med. © 2021 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

Enhanced sterilization and healing of cutaneous pseudomonas infection using 5-aminolevulinic acid as a photosensitizer with 410-nm LED light.

BACKGROUND: Pseudomonas aeruginosa (PA) frequently develops antibiotic-resistant characteristics, which is clinically problematic. The main reason behind the rise of antibiotic-resistant PA is the extensive use of antibiotics. Therefore, a novel technique is needed to treat PA infections. Photodynamic therapy (PDT) is thought to have the potential to be a non-antibiotic treatment for infections. 5-Aminolevulinic acid (ALA), which works as a photosensitizer after being metabolized into protoporphyrin IX (PpIX) in the heme synthetic pathway, is used for PDT. Thus far, the in vivo effectiveness of PDT using ALA against PA is unknown. OBJECTIVE: In this study, we investigated PDT using ALA both in vitro and in vivo. METHODS AND RESULTS: Although PDT with ALA alone did not show a bactericidal effect on PA, PDT with both ALA and EDTA-2Na had a bactericidal effect in vitro. In in vivo experiments, wounds healed faster in PA-infected mice treated with PDT using both EDTA-2Na and ALA compared to non-PDT. CONCLUSION: These results suggest that PDT with EDTA-2Na and ALA is a potential novel treatment option for PA-infected wounds.

Photodynamic therapy using systemic administration of 5-aminolevulinic acid and a 410-nm wavelength light-emitting diode for methicillin-resistant Staphylococcus aureus-infected ulcers in mice.

Bacterial resistance to antibiotics has become a worldwide problem. One potential alternative for bacterial control is photodynamic therapy. 5-aminolevulinic acid is a natural precursor of the photosensitizer protoporphyrin IX. Relatively little is known about the antibacterial efficacy of photodynamic therapy using the systemic administration of 5-aminolevulinic acid; a few reports have shown that 5-aminolevulinic acid exerts photodynamic effects on methicillin-resistant Staphylococcus aureus (MRSA) in vitro. In this study, we evaluated the effectiveness of photodynamic therapy using 5-aminolevulinic acid and a 410-nm wavelength light-emitting diode in vitro and in vivo for the treatment of MRSA. We found that 5-aminolevulinic acid photodynamic therapy with the light-emitting diode had an in-vitro bactericidal effect on MRSA. In vivo, protoporphyrin IX successfully accumulated in MRSA on ulcer surfaces after intraperitoneal administration of 5-aminolevulinic acid to mice. Furthermore, 5-aminolevulinic acid photodynamic therapy accelerated wound healing and decreased bacterial counts on ulcer surfaces; in contrast, vancomycin treatment did not accelerate wound healing. Our findings indicate that 5-aminolevulinic acid photodynamic therapy may be a new treatment option for MRSA-infected wounds.

Segmental arterial mediolysis accompanied by renal infarction and pancreatic enlargement: a case report.

INTRODUCTION: Due to recent advances in imaging diagnostic techniques, there are an increasing number of case reports of segmental arterial mediolysis. However, there are only a limited number of reports on segmental arterial mediolysis-related abnormalities of abdominal organs other than the intestine. This report describes a case of segmental arterial mediolysis accompanied by abnormalities of abdominal organs without clinical symptoms. CASE PRESENTATION: A 52-year-old Japanese man with hematuria and no prior medical history was referred to a urologist and was diagnosed as having urinary bladder cancer. He underwent trans-urethral resection of the bladder tumor and intra-vesical instillation therapy, which was followed by observation. During follow-up, although no abdominal symptoms were observed, an abdominal computed tomography scan revealed a dissection of the superior mesenteric artery. A false lumen partially occluded by a thrombus was located distal to this occlusion. The lumen was irregularly shaped with narrow and wide sections. Similar irregularities were also observed in the wall of the inferior mesenteric artery. Arterial dissection with thromboembolism in the left renal artery and renal infarction was also observed. Follow-up computed tomography after two months revealed an enlargement of the pancreatic tail adjacent to the splenic artery. Follow-up three-dimensional computed tomography showed gradual re-expansion of the true lumen of the superior mesenteric artery, improvement in arterial wall irregularities, and a reduction in the pancreas enlargement and renal infarction. Over the following 15 months, these changes gradually normalized. On the basis of the vascular changes in multiple arterial systems that resolved spontaneously, we considered that the lesions were associated with segmental arterial mediolysis. CONCLUSIONS: We present a rare case of segmental arterial mediolysis accompanied by abnormalities of abdominal organs without clinical symptoms. Three-dimensional computed tomography was useful for follow-up evaluation in our patient.

Safety and efficacy of an ultrashort-acting ß1-blocker on left ventricular dysfunction.

Landiolol hydrochloride, an ultrashort-acting ß1-selective blocker, is a highly regulated drug. This study evaluated the safety and efficacy of this drug for cases of coronary artery bypass grafting (CABG) with left ventricular dysfunction. Between September 2006 and August 2009, 32 patients with a left ventricular ejection fraction of <40% underwent CABG. Two groups of patients, a group administered landiolol hydrochloride and a control group not administered this drug, were compared. The administration of landiolol hydrochloride was initiated at 1 µg/kg per minute (γ) after cardiopulmonary bypass in on-pump cases and after completion of all the distal anastomoses in off-pump cases. We observed no significant differences between the groups with respect to preoperative patient background or incidences of complications, except for postoperative atrial fibrillation. The heart rate decreased significantly 30 minutes after landiolol hydrochloride administration, but no change was observed in arterial pressure. No change was observed in other parameters; the hemodynamics were stable. The occurrence of atrial fibrillation during the intensive care unit stay (during landiolol hydrochloride administration) was significantly lower in the administration group. The difference remained significant after multiple logistic regression analysis; landiolol hydrochloride was the sole inhibitory factor.

WITHDRAWN: Endoscopic Radial Artery Harvesting: Long-Term Results and Graft Patency Rate.

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Efficacy of propafenone hydrochloride in preventing postoperative atrial fibrillation after coronary artery bypass grafting.

BACKGROUND: Atrial fibrillation (AF) is one of the most common complications after coronary artery bypass grafting (CABG), and the incidence of postoperative AF (PAF) is estimated to range from 10% to 40%. PAF is a serious complication that is related to unstable hemodynamics, development of embolisms, patient discomfort, and increased medical costs associated with the prolongation of hospital stay. Sometimes, immediate attention is also necessary. In this study, we assessed the efficacy of treatment with the antiarrhythmic drug propafenone hydrochloride, which was administered in the early postoperative period, in preventing the development of PAF, and we attempted to identify risk factors for PAF. MATERIALS AND METHODS: The subjects were 78 patients who underwent isolated off-pump CABG between July 2007 and October 2008. We conducted the study by dividing the patients into 2 groups, a group of 26 patients who received propafenone hydrochloride (P group) and a control group of 52 patients who did not receive this drug (C group). The patients in the P group were given propafenone hydrochloride (150-450 mg/day orally) for 10 days, starting on the day after surgery, and were observed for the development of AF by means of continuous 12-lead electrocardiographic monitoring. Development of AF was defined as AF that lasted

Primary tuberculosis of the appendix in a young male patient: report of a case.

A 23-year-old man without a history of tuberculosis presented with right lower abdominal pain and a fever. An increased inflammatory response was found, and abdominal computed tomography showed a diffuse enlargement and wall thickening in the appendix. An ileocecal abscess and perforating appendicitis were suspected. Therefore, an emergency operation was performed. The surgery revealed a diffuse enlargement with adhesion to the retroperitoneum, which was suspected to be a neoplastic lesion of the appendix, thus an ileocecal resection including the appendix was performed. A histopathological examination revealed a number of epithelioid granulomas having Langerhans giant cells with caseous necrosis in the appendix, in addition to many granulomas without caseous necrosis in the regional lymph nodes. No tubercle bacilli were detected by Ziehl-Neelsen staining. Further examination revealed no tubercular lesions in other organs, thus leading to the diagnosis of primary tuberculosis of the appendix. This is an extremely rare disease reported in Japan.

Endoscopic radial artery harvesting for coronary artery bypass grafting: the initial clinical experience and results of the first 50 patients.

BACKGROUND: The radial artery (RA) is a commonly used arterial conduit in coronary artery bypass grafting (CABG). Traditional open-vessel harvest often leads to postoperative wound complications and cosmetic problems. Endoscopic RA harvesting (ERAH) has been widely used to prevent these problems. The purpose of this study was to assess these problems and graft patency in the first 50 patients who underwent ERAH. METHODS: Between February 2006 and October 2007, 50 patients underwent ERAH with the VasoView system (Boston Scientific). These patients were compared with 50 patients who underwent the traditional open technique. RESULTS: The mean age was 62.8 years in both groups. All RAs were successfully harvested. No conversion was made from ERAH to the traditional open technique. The mean harvesting time (forearm ischemic time) was 27.4 + or - 6.5 minutes, and the mean length of the RA in the ERAH group was 18.5 cm. Neither wound complications, such as wound infection and skin necrosis, nor severe neurologic complications were recorded. The patency rate was 95.9% (95/99) in the ERAH group and 94% (94/100) in the open group. CONCLUSION: ERAH can be performed safely, and the early results are satisfactory. Endoscopic vessel harvesting is therefore recommended as the technique of choice for RA harvesting.

[Perioperative management following cardiovascular surgery in patients with renal insufficiency].

In recent years as the population becomes older, the number of patients undergoing cardiovascular surgery and thereafter suffering various complications has risen with increasing severity. Renal insufficiency is one of the characteristic complications. Most cardiovascular procedures require extracorporeal circulation. With extracorporeal circulation, kidney perfusion pressure and the perfusion volume decrease and this can result in potential renal tubule disorders following surgery. Therefore, it is important to prevent the postoperative aggravation of the renal function in patients with renal dysfunction before the induction of dialysis because they have a diminished renal reserve capacity and specific management is also required for patients on dialysis. The important points are as follows; (1) for the patient who is not on dialysis, it is important to maintain a sufficient blood pressure and prevent a shift to dialysis by avoiding exsiccation, (2) for the patient on dialysis, it is important to carefully evaluate the situation for each patient before resuming dialysis after surgery, (3) for both patient populations, it is important to always consider the dosage and dosage interval when any drugs are administered.

New method of thermal coronary angiography for intraoperative patency control in off-pump and on-pump coronary artery bypass grafting.

BACKGROUND: We evaluated the effectiveness of a new thermal coronary angiogram system using intraoperative imaging with an infrared camera for coronary artery bypass grafting. METHODS: The thermal coronary angiograms of 51 patients who underwent a total of 107 coronary artery bypass grafts were evaluated. Thermal coronary angiograms were obtained after completing distal anastomoses by the injection of cold saline solution into the vein grafts or free arterial grafts or by reperfusion with warmer blood in the internal thoracic artery grafts. Temperature differences of greater than 0.1 degrees C between the injectant and the epimyocardium resulted in high-contrast images. RESULTS: Thermal coronary angiograms were obtained from 107 coronary artery bypass grafts; 103 grafts were patent (96.3%), and 2 internal thoracic artery grafts were occluded. After reanastomoses, thermal coronary angiograms were again obtained, and all grafts appeared to be patent. Four grafts did not clearly show hemokinesis because of an intramyocardial segment or circumferential fat surrounding the artery. CONCLUSIONS: Thermal coronary angiograms cannot show hemokinesis clearly in cases with an intramyocardial arterial segment or in patients in whom the grafts are surrounded by fat. Therefore, thermal coronary angiograms are considered to play a valuable role in confirming the success or failure of myocardium revascularization because this diagnostic modality does not interfere with the surgical procedures, is noninvasive, and can be both quickly and easily performed.

Coronary artery bypass grafting in DES era.

Coronary artery bypass grafting (CABG) has played an important role in the treatment of ischemic heart disease. Recently, the introduction of a drug-eluting stent (DES) has decreased the incidence of restenosis after percutaneous intervention (PCI). PCI with a DES is being increasingly performed, whereas the number of patients for whom CABG has been indicated has decreased over the last few years in Japan and the United States. According to a report, the number of patients undergoing CABG will not decrease in the future due to its usefulness in the treatment of multi-vessel lesions. We have also reviewed how CABG should be improved. For this purpose, it may be important to carry out less invasive CABG by the off-pump method and to improve the long-term results obtained by CABG with an internal thoracic artery graft and complete revascularization. Hence, CABG may achieve better long-term results compared with PCI and continued future application of CABG.

Application of a new suture material called the U-Clip for composite and sequential grafting with off-pump coronary bypass surgery.

BACKGROUND: The U-Clip was found to facilitate the interrupted anastomosis of coronary artery bypass grafts (CABG). This device may be beneficial especially in multivessel off-pump CABG (OPCAB) using composite grafts or sequential anastomosis. The aim of this study was to evaluate our early clinical experience using the U-Clip in OPCAB cases. METHODS: This retrospective study included 118 patients who underwent off-pump CABG between 2001 and 2004. The mean age of the 91 men and 27 women was 69.5 +/- 8.0 years (range, 47-85). The U-Clip was adopted for sewing 73 proximal ends of the free graft to the side or end of the inflow conduit to prepare the composite graft. The U-Clip was also applied to 112 distal anastomoses, especially to the side-to-side anastomosis of the sequential graft. RESULTS: Hospital mortality rate was 0.8% (1/118). The early patency rate of distal anastomoses using the U-Clip was 95% (96/101). The early patency rate of proximal anastomoses using the U-Clip was 98.4% (62/63). Interim angiography was performed in 12 patients (range, 3.8-42 months; average, 16 months). In these 12 patients, a total of 8 proximal anastomoses of conduits using the U-Clip were all patent without stenosis. The patency rate of a total of 10 distal anastomoses in the 12 patients using the U-Clip was 100%. CONCLUSIONS: The U-Clip-interrupted anastomosis enables a safe, definite, and rapid end-to-end or end-to-side connection of arterial grafts. We therefore consider the U-Clip to be a useful suture material especially for multivessel OPCAB using multiple arterial grafts.

Central arterial cannulation and the arch first method for aortic arch aneurysm repair.

BACKGROUND: We investigated whether the axillary artery or ascending aorta cannulation combined with the arch first method decreases the risk of stroke during total arch replacement. PATIENTS AND METHODS: From January 2002 to January 2006, 35 total arch replacements were performed with the arch first method and central arterial cannulation. The mean age was 66+/-10 years. The cannulation sites were the axillary artery in 19 and the ascending aorta in 16. The arch first method (a short period of deep hypothermic circulatory arrest with retrograde cerebral perfusion and then subsequent antegrade cerebral perfusion) was used in all patients. RESULTS: The mean retrograde cerebral perfusion time was 29+/-7 min. The incidence of the permanent neurological dysfunction related to the surgical procedures was 2.9% (1/35). Hospital mortality was 5.7% of patients (2/35). There was no difference in the operative outcome between the 2 arterial inflow sites. CONCLUSION: At the time of total arch replacement, the use of central arterial cannulation and the arch first method are effective methods for preventing permanent brain injury. Cannulation of the ascending aortic using Dispersion cannula perfusing toward the aortic valve is considered to be a safe and favorable method for central arterial cannulation.

Pulsed dye laser treatment for linear scars with concave and erythematous appearance.

Facial linear scars with concave and erythematous appearance sometimes occur after long observation even if adequate conservative treatments have been applied. Because the regenerated epithelium is thin, those scars are seen as red or pink, and are sometimes accompanied with postinflammatory hyperpigmentation. For these scars, flashlamp-pumped pulsed dye of the wavelength of 585 nm and pulse-width of 450 micro s was used, and acceptable results were obtained. Three cases required one treatment and one case needed two, and any side effects were not recognized. Compared with the carbon dioxide laser, which often shows severe scarring as a side effect, the pulsed dye laser with a short down time is useful.

Alterations and diversity in the cytoplasmic tail of the fusion protein of subacute sclerosing panencephalitis virus strains isolated in Osaka, Japan.

We determined the nucleotide sequence of the fusion (F) gene of three strains (Osaka-1, -2, and -3) of nonproductive variants of measles virus (MV). These viral strains were isolated in Osaka, Japan, from brain tissues of patients with subacute sclerosing panencephalitis (SSPE). Phylogenetic analysis revealed a close relationship among the three strains of SSPE virus. The cytoplasmic tail of the F protein, predicted from sequence analysis of the gene, is altered in all three SSPE strains when compared to the MV field strains. However, the extent and mode of alteration are different in each strain. The F protein of the Osaka-1 strain has six nonconservative amino acid substitutions and a 29-residue elongation of its cytoplasmic tail. The F protein of the Osaka-3 strain has two nonconservative substitutions and a 5-residue truncation of its C-terminus. Although the termination codon is not altered in the F protein of the Osaka-2 strain, five or six amino acids are changed in the cytoplasmic tail of the F protein of the two sibling viruses of this strain. The significance of the altered cytoplasmic domain of the SSPE viruses in the SSPE pathogenesis is discussed.

Comparison of the neuropathogenicity of two SSPE sibling viruses of the Osaka-2 strain isolated with Vero and B95a cells.

Two sibling viruses, Fr/V and Fr/B, of the subacute sclerosing panencephalitis (SSPE) virus Osaka-2 strain were isolated from a small biopsy specimen of the brain of an SSPE patient by cocultivation with two different cell lines, Vero and B95a cells, respectively. These two sibling viruses differ from each other in their molecular mechanisms of defective M protein expression. In this study, we found that the Fr/B virus could scarcely form syncytium foci on Vero cells, although the Fr/V virus could do so on both Vero and B95a cells, showing a similar relation of cell tropism between recent field isolates and laboratory strains of the measles virus. Severe neurovirulence of both Fr/V and Fr/B viruses was observed in hamsters inoculated intracerebrally with less than 100 PFU, in contrast to the negative neurological and pathological findings in hamsters inoculated even with more than 10(5) PFU of their possible progenitor measles virus. Comparative sequence analysis of inoculated viruses and reisolated viruses from diseased hamster brains showed few variations at a region containing the P-M gene junction, indicating that the inoculated viruses propagated in the brains and induced neurovirulence. All these results suggest that SSPE virus isolated with a lymphoid cell line is similar in neuropathogenicity to that isolated with a nonlymphoid cell lines, irrespective of differences in the molecular mechanism of M protein defectiveness.