Mogamulizumab-induced photosensitivity in patients with mycosis fungoides and other T-cell neoplasms.

BACKGROUND: Mogamulizumab (Mog) is a defucosylated, therapeutic monoclonal antibody, targeting CCR4 and was first approved in Japan for the treatment of adult T-cell leukaemia/lymphoma (ATLL), followed by cutaneous T-cell lymphoma and peripheral T-cell lymphoma. OBJECTIVE: To retrospectively investigate development of photosensitivity in patients with mycosis fungoides and other T-cell neoplasms after treatment with Mog. METHODS: We treated seven cutaneous lymphoma patients with Mog. Upon combination treatment with narrow-band UVB, we noticed that four patients developed photosensitivity dermatitis following Mog therapy, including two cases of mycosis fungoides, one case of adult T-cell leukaemia/lymphoma and one case of EB virus-associated T-cell lymphoproliferative disorder. Phototest was performed with UVA and UVB, and immunohistochemical staining for CD4, CD8 and Foxp3 was conducted in both photosensitivity and lymphoma lesions. RESULTS: Phototest revealed that the action spectrum of the photosensitivity was UVB in three cases and both UVB and UVA in one case. Histopathologically, the photosensitive lesions were characterized by a lichenoid tissue reaction with a CD8+ T cell-dominant infiltrate, sharing the feature with chronic actinic dermatitis, an autoreactive photodermatosis with a cytotoxic T-cell response. Foxp3+ regulatory T cells (Tregs) were decreased in the photosensitivity lesions compared with the lymphoma lesions. CONCLUSION: Increased incidence of photosensitivity reaction was observed during Mog treatment. Decreased number of Tregs in the lesional skin suggests that this reaction is possibly induced by autoreactive cytotoxic T cells.

Propionimicrobium lymphophilum and Actinotignum schaalii bacteraemia: a case report.

Propionimicrobium lymphophilum is an anaerobic Gram-positive bacillus that exists in human skin and urinary tract. The pathogenicity is, however, not well known. Only two cases of urinary tract infection have been described recently. In the case presented here, the bacterium was isolated, concomitant with Actinotignum schaalii, from blood culture of a patient with fever and difficulty of urination. The bacteria were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA sequencing. The case was successfully treated with ampicillin/sulbactam.

Clinical features of Bacteroides bacteremia and their association with colorectal carcinoma.

PURPOSE: We investigated the clinical features of Bacteroides bacteremia for 5 years to determine the risk factors for mortality and to ascertain whether bacteremia due to Bacteroides spp. is associated with colorectal carcinoma. METHODS: This study comprised a review of all patients with Bacteroides bacteremia at a teaching hospital in Tokyo from April 2003 to March 2008. We also conducted a case-control study between Bacteroides bacteremia and bacteremia due to other pathogens. RESULTS: During the study period, 25 cases of bacteremia were due to Bacteroides spp. Bacteroides bacteremia was associated with a high mortality rate (24%). Malignancy (76%) was the major comorbidity, followed by a history of surgery (40%). Colorectal carcinoma was the most frequent (n = 8, 32%) of the comorbid malignancies and was recognized as the primary infection site in six cases. Prevalence of colorectal carcinoma as comorbidity was significantly higher in Bacteroides bacteremia than in other bacteremia. CONCLUSIONS: In the Bacteroides bacteremia cases of this study, colorectal carcinoma was the major comorbidity and primary infection site. Colorectal carcinoma screening in Bacteroides bacteremia patients is potentially an important diagnostic marker for the early detection of this infection in the future.

Complete atrioventricular septal defect associated with tetralogy of fallot: surgical indications and results.

Complete atrioventricular septal defect (AVSD) associated with tetralogy of Fallot is a rare condition that still has problems in the postoperative period. The authors report their surgical experiences over the past 10 years. Nine children underwent total correction. The defect was repaired by the 2-patch technique and the ATrioventricular valve was reconstructed by suturing the cleft and annuloplasty. A transannular right ventricular outflow patch was used in 5 patients. All patients had Down syndrome and a free-floating superior bridging lEAflet. One patient died from cardiac failure. Although there was no reoperation or death in the late postoperative periods, mild mitral regurgitation occurred in 4 patients and there was moderate or severe pulmonary regurgitation in 2 patients. All survivors currently have no critical symptoms in their daily lives. With the standard of patient selection used, the optimal body weight was around 8 kg and PA index was 200 or more. Right ventriculotomy provided a better view for complete closure of the ventricular septal defect (VSD). In order to avoid re-regurgitation of the atrioventricular valve, the 2-patch technique is the most suitable procedure for total repair.

[Exercise capacity in children late after aortic valve replacement using the Konno procedure].

Between 1980 and 1996, aortic valve replacements using the Konno procedure were performed in 10 patients. In order to assess the latent problems after this procedure, the exercise capacity was evaluated in 6 patients (3 males and 3 females). Exercise stress tests by a bicycle ergometer with ramp protocol were performed and gas exchange responses using the mixing chamber method were measured. The mean age at the time of operation was 6.6 years (range 3 to 11) and the mean age at the time of exercise test was 11.4 years (range 8 to 15). All patients were NYHA class I except 2 patients who had residual PH. Maximum oxygen consumptions were 37 to 39 ml/kg/min in males and 23 to 34 ml/kg/min in females. Maximum heart rates ranged from 166 to 184 bpm and O2 pulses ranged from 4.6 to 7.1 ml/beat/BSA. In the 2 patients who had residual pulmonary hypertension, HR bursting and O2 pulse plateau & decline occurred, which may indicate presence of decreased stroke volume. In conclusion, all patients late after the Konno procedure could tolerate exercise beyond respiratory compensation and there were no arrhythmia during exercise. HR was satisfactorily increased but maximum oxygen consumption was lowered at about 70% of the normal level.

Predisposing factors of valve regurgitation in complete atrioventricular septal defect.

OBJECTIVES: We sought to determine the intrinsic risk factors of valve regurgitation in complete atrioventricular septal defect. BACKGROUND: Progression of regurgitation varies in each case, although the structure of the common atrioventricular valve itself is a predisposing factor. METHODS: In 90 consecutive patients undergoing surgical repair, we evaluated the preoperative and postoperative regurgitation, valve morphology, age at surgery and associated anomalies. A regurgitation jet with a high velocity reaching the deep left atrial wall by echocardiography was estimated as marked regurgitation. RESULTS: None of the 40 patients with Rastelli type C and an undivided inferior bridging leaflet had preoperative regurgitation in the first year of life, and 12% of them (95% confidence intervals [CI]: 0% to 28%) showed regurgitation at the age of 2. Of the remaining 50 with Rastelli type A and/or a divided inferior leaflet, regurgitation was determined in 21% (95% CI: 6% to 35%) of those 1 year old and in 49% (95% CI: 29%7 to 69%) of those 2 years old (p < 0.01). All patients underwent corrective surgery using the double-patch technique, with the "cleft" being sutured adequately. Irrespective of the valve morphology, regurgitation remained in 52% (12 of 23) of those with preoperative regurgitation, whereas regurgitation developed postoperatively in 28% (16 of 58) of those without regurgitation (p < 0.001). CONCLUSIONS: Those with Rastelli type C and an undivided inferior leaflet had a lesser degree of progression of preoperative regurgitation. However, regurgitation was likely to exist even after adequate repair once regurgitation had already advanced. Therefore, early primary repair before progression of the regurgitation may be the key to maintaining better competence of the atrioventricular valve.

Interventricular communication in complete atrioventricular septal defect.

BACKGROUND: Little attention has been paid to whether the interventricular communication in complete atrioventricular septal defect is different beneath the superior and inferior bridging leaflets, a feature of obvious surgical significance. METHODS: We searched for a defect under the bridging leaflets and examined the valve morphologies in 98 autopsied and 86 surgical patients. Of the overall specimens, 27 were associated with Fallot's tetralogy, and a further 20 had subaortic stenosis, aortic coarctation, or both. In the autopsied specimens, we also measured the degree of deficiency of the ventricular septum. RESULTS: No communication was found under the inferior bridging leaflet in 30% (29 of 98) of the specimens. All 29 hearts except two without such communications showed an undivided inferior leaflet. In contrast, all patients undergoing operation except 1 had a communication beneath both bridging leaflets (p < 0.001). The absence of a communication beneath the inferior leaflet was observed more in hearts with Fallot's tetralogy (seven of 14) or those with subaortic stenosis, aortic coarctation, or both (eight of 18) than in those without associated anomalies (14 of 66; p < 0.01). Those with a communication under the inferior leaflet showed a greater deficiency of the inlet ventricular septum than did those without it (p < 0.001). CONCLUSIONS: In a certain percentage of patients with complete atrioventricular septal defect, there will be no communication under the inferior bridging leaflet. Surgeons should be aware of this possibility, particularly when confronted with a patient with obstruction in either ventricular outlet.

Morphometric analysis of atrioventricular septal defect with common valve orifice.

OBJECTIVES: We sought to analyze morphometric features of atrioventricular septal defect (AVSD) in autopsy specimens and to consider the developmental implications of obstruction in either ventricular outflow tract. BACKGROUND: Left ventricular outlet obstruction (LVO) is more prevalent in patients with Rastelli type A morphology. When tetralogy of Fallot (ToF) complicates this malformation, there is usually a free-floating superior bridging leaflet. The reasons for these associations are uncertain. METHODS: In 133 hearts with AVSD and common atrioventricular (AV) valve orifice, we measured the degrees of horizontal and anterior deviation of the great arteries from the AV valve, the diameters of the ventricular outlets and the great arteries and the degree of deficiency of the ventricular septum. RESULTS: In Rastelli type A morphology, the great arteries were deviated more leftward than in type C morphology (p < 0.01). Type A hearts also had a relatively small aorta, with a long and narrow subaortic tract. The presence of obstruction in either ventricular outlet was associated with a more oblique arrangement of the great arteries, with the pulmonary trunk being more leftward than in hearts without LVO (p < 0.01). In combination with ToF, the aorta was dextroposed and the pulmonary trunk was located more posteriorly (p < 0.01). No heart with type A morphology showed ToF (p < 0.01). CONCLUSIONS: The geometric arrangement of the great arteries correlated significantly with obstruction in either ventricular outflow tract and with the Rastelli subtypes. Malrotation of the developing outlet septum may be an embryologic factor producing obstruction, with horizontal deviation of the outlets also influencing the morphology of the superior bridging leaflet.

[Successful surgical correction for an incomplete endocardial cushion defect in an elderly patient].

A 72-year-old female who presented with symptoms of severe congestive heart failure, was subsequently diagnosed as having an incomplete endocardial cushion defect. A severe left-to-right shunt and mitral and tricuspid valve regurgitation were noted. Closure of the ostium primum defect, mitral valve replacement, and tricuspid valve annuloplasty were performed simultaneously. The postoperative course was uneventful. A review of literature revealed that this is the oldest such surgical patient described in Japan to date. We believe that surgical correction can be effective even in elderly patients.

[One-stage surgery for Stanford type-A aortic dissection, annulo-aortic ectasia, and chronic constrictive pericarditis--a case report].

A case is reported of a rare combination of chronic constrictive pericarditis and aortic dissection. A 23-year-old male was diagnosed with constrictive pericarditis and annulo-aortic ectasia concomitant with type-A dissection. A pericardiectomy was performed under cardiopulmonary bypass, and an aortic segment, from the root to the arch, was totally replaced by a composite graft using selective cerebral perfusion. Both procedures were performed in one stage. An aged clot was found in the pericardial cavity. Sustained rupture of the aortic dissection into the pericardial cavity is considered to be a possible explanation for the development of constrictive pericarditis. The postoperative course was uneventful and the patient was discharged 34 days after the operation.

[Open heart surgery without homologous blood transfusion for tetralogy of Fallot--use of hydroxyethyl starch diminishes the necessity of protein transfusion].

To avoid any blood or protein transfusions, we employed 6% hydroxyethyl starch in 0.9% saline (saline HES) during cardiopulmonary bypass (CPB) for intracardiac repair in 24 consecutive patients with Tetralogy of Fallot (TF). The postoperative course has been satisfactory (central venous pressure 9.5 +/- 1.2 cmH2O, duration of intubation after surgery 4.4 +/- 1.5 hours), and all patients but one did not require transfusion therapy during their hospital stay. We conclude that intracardiac repair without transfusions is feasible in almost all patients with TF, when substituting saline HES for blood or proteins.

Properties of yeast expressed Aspergillus nidulans chitin synthase B which is essential for hyphal growth.

A complementary DNA of the Aspergillus nidulans chsB gene encoding chitin synthase, an essential gene for hyphal growth, was obtained by RT-PCR and expressed in Saccharomyces cerevisiae by using the GAL1 promoter in a multicopy plasmid. The biochemical characteristics of chitin synthase B (ChsB) expressed in S. cerevisiae were examined. The chitin synthase B produced in galactose medium showed zymogenicity due to activation by trypsin treatment and required Mg2+ ion to exert maximal activity. It was competitively inhibited by polyoxin D. The Ki value of the inhibitor was 10 microM, and the K(m) for the substrate was 1.6 mM. The activity was enhanced by the addition of N-acetylglucosamine. The optimal pH is 7.5 when Mg2+ is used. These characteristics are the same as those of other chitin synthases.

[Open heart surgery without blood transfusion for complete atrioventricular septal defect associated with tetralogy of Fallot].

Open heart surgery without blood transfusion was successfully performed in two patients with complete atrioventricular septal defect associated with tetralogy of Fallot. The postoperative hemodynamics and respiratory status were uneventful in both patients (central venous pressure after ICU admission: 13.7 cmH2O and 11.5 cmH2O, intubation time after surgery: 9 hours and 11 hours). Autologous blood donation immediately after induction of anesthesia and minimization of bypass circuit were effective methods for open heart surgery without blood transfusion, particularly in cyanotic patients requiring prolonged cardiopulmonary bypass for intracardiac repair.

Right heart growth after the Bjork connection in tricuspid atresia.

BACKGROUND: Atrioventricular (Bjork) connection used for the correction of tricuspid atresia has become of little more than historical interest. However, the optimal form of management of patients undergoing this repair still requires continued assessment of the long-term outcome. We review our experience with valveless atrioventricular connection focusing on the morphological changes seen in the heart chambers. METHODS: Between October 1978 and March 1986, seven patients with tricuspid atresia having concordant ventriculoarterial connection underwent atrioventricular connection. Configuration of the surgical connection included Dacron extracardiac conduit without valve insertion. End-diastolic volumes were calculated in the respective heart chambers. A group of patients undergoing atriopulmonary connection was used as control subjects. RESULTS: The diminutive right ventricle showed conspicuous growth at 1.1 +/- 1.1 years after the initial repair, with the end-diastolic volume index increasing from 25.0 +/- 8.7% of normal value at a preoperative state to 80.4 +/- 31.1% of normal value postoperatively. Further operation was done in three patients because of the obstructive atrioventricular pathway. At reoperation, reconstruction of the connection with an addition of either atriopulmonary or cavopulmonary anastomosis afforded clinical improvement in our series. CONCLUSIONS: This study suggests that volume load resulting from the widely patent atrioventricular connection combined with backward regurgitation affects the development of young heart muscle of the right ventricle. The optimal choice of surgical strategy should be made at reintervention through recognition of the particular postsurgical anatomy.

Inhibition of hepatitis-B-virus core promoter by p53: implications for carcinogenesis in hepatocytes.

The incidence of hepatocellular carcinoma (HCC) is particularly high in regions of Asia and sub-Saharan Africa where rates of infection with human hepatitis-B virus (HBV) and aflatoxin-B1 contamination of food are high. In HCC tumors occurring in inhabitants of these regions, a G-to-T mutation frequently occurs at position 249 of the tumor-suppressor gene p53. This suggests that HBV and p53 mutation may collaborate in the carcinogenic process in liver. We have examined the effect of the HBV protein HBX in HCC lines with exogenous wild-type p53 or mutated p53 on transactivation of 2 different reporter genes. Transfection of HCC lines with wild-type p53 and a reporter with the promoter from the p53-responsive gene WAF1/p21 resulted in a high level of expression, as expected. When cells were co-transfected with a reporter gene driven by the HBV core promoter and with the HBX gene, expression was enhanced in the Hep 3B, HLE, PLC/PRF/5 and HuH 7 lines, but not in the HuH 1 line. Co-transfection of the reporter with a plasmid containing wild-type p53 resulted in significant inhibition of the HBV core promoter in all of the lines, whereas the mutated p53 gene had no effect. Our results indicate that wild-type p53 can inhibit transcription from the HBV core promoter. In similar experiments, both HBX and p53 were co-transfected into HCC lines with the WAF1/p2l reporter gene. HBX inhibited p53-induced expression in 4 of the 6 lines (Hep 3B, HuH 1, HuH 7 and HLE), there was no effect in one line (HLF), and enhancement was evident in PLC/PRF/5. Our results indicate that inhibition of p53 transcriptional activity by HBX does occur in HCC, but is highly cell-context-dependent. Inhibition of transcription from the HBV core promoter by wild-type p53 appears to be more universal, and may represent a mechanism by which wild-type p53 can protect against the carcinogenic process in liver.

[Open heart surgery with bloodless priming for cyanotic congenital heart diseases--the role of autologous blood donation after induction of anesthesia].

In 50 patients with cyanotic congenital heart diseases, open heart surgery was conducted with bloodless priming from January 1994 to August 1995. Surgical procedures included the Rastelli procedure (n = 14), the modified Fontan procedure (n = 10), and intracardiac repair of TOF (n = 26). The non-transfusion rate from January 1994 to August 1994 was 17% (1/6) in the Rastelli group, 67% (2/3) in the Fontan group, and 67% (8/12) in the TOF group. Autologous blood donation immediately after induction of anesthesia was carried out from September 1994 because post-operative hemorrhage and severe hemolysis of residual blood of the pump required conventional blood transfusions up to August. Autologous blood of 12 +/- 2 ml/kg could be collected, and the non-transfusion rate from September 1994 to August 1995 was increased to 75% (6/8) in the Rastelli group, 86% (6/7) in the Fontan group, and 93% (13/14) in the TOF group. There were no complications due to asanguineous extracorporeal circulation or autologous blood donation, and the post-operative hemodynamic and respiratory status were uneventful in almost all cases. We conclude that open heart surgery without blood transfusion is feasible in more than 70-80% patients who undergo the Rastelli procedure, the modified Fontan procedure or intracardiac repair of TOF. Autologous blood donation after induction of anesthesia proved to be highly effective method for reducing conventional blood transfusion.

[Axillo-iliac bypass grafting for reoperation of graft stenosis after aortic arch reconstruction of type B interruption of the aortic arch: two cases report].

Right axillo-iliac bypass grafting was performed in two females (10 and 14 years old) who had stenosis or obstruction of grafts after reconstruction of the aortic arch in type B interruption. The initial bypass operations were carried out at the age of 5 months and 5 years, with the use of a 5-mm EPTFE graft and a 10-mm Dacron graft. Nine years later, the EPTFE graft was completely obstructed, and the Dacron bypass has stenosis, kink and calcification. To minimize surgical invasion, axillo-iliac extra-anatomical bypass was employed in both patients. 8-mm or 10-mm Hemashield grafts were implanted between the right axillar artery and the right common iliac artery through the intrapleural-preperitoneal route, and favourable results were obtained in both patients. The axillo-iliac bypass is considered to be a beneficial conservative method of reoperation for stenosis after graft reconstruction of the aortic arch in the younger age patients.

[Open heart surgery with bloodless priming for ventricular septal defect and pulmonary hypertension].

In 17 patients with ventricular septal defect and pulmonary hypertension (VSD, PH) weighing 5.2 kg to 9.5 kg, open heart surgery was conducted with bloodless priming (total priming volume: 370-470 ml). None of the patients required blood transfusion during their hospital stay. The post-operative respiratory status was excellent in all cases with duration of intubation being 6 +/- 3 hours. While 12 patients weighing over 6.6 kg maintained individual constant hematocrit (Hct) values during cardiopulmonary bypass (CPB), all 5 patients weighing under 6.1 kg showed significant decrease during rewarming (17 +/- 2% after initiation of CPB to 14 +/- 2% during rewarming). The lowest Hct value was 12% during rewarming in 6.0 kg infant. The pre-operative circulating blood volume (CBV) was calculated retrospectively from the priming volume, the Hct value after anesthetic induction and the Hct value after initiation of CPB. The relationship, CBV (ml) = body weight (kg) x 72-13 (r = 0.85, p < 0.01) was derived. Using this equation, we calculated the predicted Hct level after initiation of CPB using the 370 ml bypass circuit in 43 VSD PH patients weighing 3.4 kg-5.9 kg. The Hct values were 17 +/- 2% in 13 patients weighing over 5 kg with 12 (91 percent) above 15%, and 13 +/- 2% in 30 patients weighing under 4 kg with 3 (11 percent) above 15%. Hct levels of 34%-36% before CPB were essential in patients weighing 4.0 kg-4.9 kg for the Hct level after initiation of CPB to exceed 15%.(ABSTRACT TRUNCATED AT 250 WORDS)