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The risk of developing severe COVID-19 illness despite completing vaccination for patients who have previously received immunosuppressive therapy is unclear.We present three patients who received rituximab for treatment of autoimmune disorders who subsequently developed severe COVID-19 pneumonia post-vaccination requiring intensive care unit admission and found to have undetectable B cells.While there have been concerns about the effectiveness of COVID-19 vaccines in this patient cohort, this is the first case series to report development of severe COVID-19 illness after completing vaccination in those who previously received rituximab. Guidelines for the optimal timing of COVID-19 vaccination in relation to immunosuppressive therapy have been recently published, albeit after many patients in this subpopulation have already been vaccinated.This case series brings attention to the limited humoral response to vaccines in patients treated with rituximab, highlights existing guidelines and their limitations, and raises future considerations about the potential benefits to testing vaccine responsiveness.

Background Biofilm formation on endotracheal tubes (ETTs) is an early and frequent event in mechanically ventilated patients. The biofilm is believed to act as a reservoir for infecting microorganisms and thereby contribute to development and relapses of ventilator-associated pneumonia (VAP). Once a biofilm has formed on an ETT surface, it is difficult to eradicate. This clinical study aimed to compare biofilm formation on three widely used ETTs with different surface properties and to explore factors potentially predictive of biofilm formation. Methods We compared the grade of biofilm formation on ETTs made of uncoated polyvinyl chloride (PVC), silicone-coated PVC, and PVC coated with noble metals after > 24 h of mechanical ventilation in critically ill patients. The comparison was based on scanning electron microscopy of ETT surfaces, biofilm grading, surveillance and biofilm cultures, and occurrence of VAP. Results High-grade (score ≥ 7) biofilm formation on the ETTs was associated with development of VAP (OR 4.17 [95% CI 1.14–15.3], p = 0.031). Compared to uncoated PVC ETTs, the silicone-coated and noble-metal-coated PVC ETTs were independently associated with reduced high-grade biofilm formation (OR 0.18 [95% CI 0.06–0.59], p = 0.005, and OR 0.34 [95% CI 0.13–0.93], p = 0.036, respectively). No significant difference was observed between silicon-coated ETTs and noble-metal-coated ETTs (OR 0.54 [95% CI 0.17–1.65], p = 0.278). In 60% of the oropharyngeal cultures and 58% of the endotracheal cultures collected at intubation, the same microorganism was found in the ETT biofilm at extubation. In patients who developed VAP, the causative microbe remained in the biofilm in 56% of cases, despite appropriate antibiotic therapy. High-grade biofilm formation on ETTs was not predicted by either colonization with common VAP pathogens in surveillance cultures or duration of invasive ventilation. Conclusion High-grade biofilm formation on ETTs was associated with development of VAP. Compared to the uncoated PVC ETTs, the silicone-coated and noble-metal-coated PVC ETTs were independently associated with reduced high-grade biofilm formation. Further research on methods to prevent, monitor, and manage biofilm occurrence is needed. Trial registration ClinicalTrials.gov NCT02284438. Retrospectively registered on 21 October 2014.

The patient was a 68-year-old man who had an anal fistula for10 years. He was referred to our institution after visiting a local physician with left femoral pain as the main complaint and received a diagnosis of high inflammatory response. We then found discharge of pus in the perianal region during a medical examination. We also found an extensive intrapelvic tumor during a computed tomography(CT)/magnetic resonance imaging examination. In addition, the level ofa tumor marker and inflammatory response were high. To control the inflammation, we performed seton drainage and sigmoid colostomy. On the basis of the pathological findings from the mucus component, we confirmed a diagnosis of fistula cancer. Considering that the progressive lesion had extensively spread, we decided to initiate chemotherapy alone because ofthe absence ofan indication for radiotherapy. We administered bevacizumab plus mFOLFOX6, and partial response was observed on a CT scan. We could control the progression ofthe disease for6 months. The present case suggests that bevacizumab plus mFOLFOX6 can be an effective regimen for unresectable advanced fistula cancers.

腎移植後2年10か月目に緑膿菌による尿路感染症でショック状態となった18歳男性に，持続性血液透析濾過とエンドトキシン吸着療法を直列回路にて施行し，奏功した症例を経験した。急性血液浄化療法を始める前に，すでに体重比10%を超える水分負荷が行われて肺水腫，低血圧の状態であったが，上記方法はfluid resuscitationに反応しない低血圧と溢水の改善に有効であった。腎移植後の尿路感染症のような特殊病態に対する，過剰な水分負荷は慎重に行うべきであり，負荷後にすぐに急性血液浄化療法が施行できる体制下で行われなければ非常に危険である。

We studied changes in the drug resistance of 606 strains of Haemophilus influenzae (H. influenzae) and 502 strains of Streptococcus pneumoniae (S. pneumoniae) isolated from our patients between 1997 and 2006. The incidence of beta-lactamase nonproducing ampicillin-susceptible H. influenzae (BLNAS) in 1997-1998 and 1999-2000 was 72.0 and 69.6%, respectively. In 2005-2006, the incidence of BLNAS decreased to 31.0%, while that of beta-lactamase nonproducing ampicillin-resistant H. influenzae (BLNAR) and intermediate-resistant H. influenzae increased to 65.5%. Remarkably early development of BLNAR and intermediate-resistant H. influenzae was found in patients younger than 3 years, as compared to patients older than 3 years. The proportion of penicillin-susceptible S. pneumoniae (PSSP) in 1999-2000 was 18.4%. In 2005-2006, the proportions of penicillin-resistant S. pneumoniae (PRSP) and penicillin-intermediate S. pneumoniae (PISP) were lower, while that of PSSP increased to 38.2%. An early increase in the proportion of PSSP was found in patients older than 3 years, as compared to patients younger than 3 years. The difference between age groups may be attributed to entrance into nursery school, frequent administration of antibiotics, and the immature immunological state of patients younger than 3 years. Therefore, changes in the drug resistance of H. influenzae and S. pneumoniae should be investigated separately, depending on the age of the patients. The minimum inhibitory concentrations of antibiotics, including cefditoren and cefcapene, against BLNAR and PRSP did not increase. The marked increase in intermediate-resistant H. influenzae and BLNAR mandates a re-evaluation of the directions for antibacterial agents.

We previously reported that provision of immediate enteral nutrition (EN) with a certain amount of omega (omega)-3 fatty acids (FAs) in patients after esophageal cancer surgery resulted in reduced platelet aggregation, coagulation activity, and cytokine production. We investigated whether EN using immuno-enhanced diet (IED) containing a large amount of omega-3 FAs as well as arginine and RNA affected the above-described responses. We also attempted to reveal whether arginine in the IED can potentially harm patients who undergo esophageal cancer surgery. Twenty-nine patients with esophageal cancer who underwent similar surgical procedures were selected. All patients received EN starting immediately after surgery. Fourteen patients received the formula with fewer omega-3 FAs, and fifteen patients received the IED. Administration of the IED tended to inhibit postoperative decrease in platelet count. Prothrombin activity and thrombin-antithrombin III complex levels were significantly reduced in the IED group. Plasma IL-8 levels were significantly lower (P < 0.05) in patients without the IED on the fifth postoperative day (POD). The proportion of T-cells was significantly higher (P < 0.05) in the IED group on PODs 1 and 7. Nitrate/nitrite levels did not differ significantly between the two groups. Early EN with an IED may enhance the inhibitory effects on postoperative platelet aggregation and hypercoagulation, and appeared to be advantageous to T-cell proliferation. These effects are expected to be beneficial in patients at risk of developing infectious complications. This study also showed that the IED could be safely used without any adverse effects for patients early after a radical surgery for the esophageal cancer.

症例は56歳，男性．2004年9月，小腸GIST疑いで待機手術の予定であったが，白血球数，CRPの上昇，腹部の圧痛を認め，腫瘍穿孔による汎発性腹膜炎の診断で，緊急に腸間膜腫瘍切除，空腸部分切除，腹腔内洗浄，ドレナージ術を施行した．病理組織学的検査で腸間膜デスモイドと診断された．退院後，外来で経過観察としたが，2006年5月，術後20カ月に再発を認め，当科で再切除を行った．再切除後，小腸の広範囲切除により，短腸症候群となったが，内服薬でコントロールされ，63病日に退院した．外来，近医での点滴治療で経過観察としたが，既往のパーキンソン症候群の進行と短腸症候群による栄養状態の悪化により，再手術後5カ月で死亡した．

Background: There are few published reports on kidney transplantation (KT) in physically handicapped patients with mental retardation. The aim of this study is to clearly identify the outcome of KT in these patients and clarify whether handicapped patients can be candidates for KT. Methods: Our study identified 25 multiply handicapped transplant recipients from 8 institutions. Causes of mental retardation were chromosomal abnormality in 5 patients, genetic syndrome in 10 patients, developmental brain anomaly in 2 patients, and other or unknown causes in 8 patients. Primary diseases leading to end-stage renal disease were congenital urinary tract anomaly in 12 patients, focal segmental glomerulosclerosis in 3 patients, cystic kidney disease in 3 patients, and other in 7 patients. Results: Twenty-three patients received living-related transplants from a parent and 2 patients received cadaver transplants. Twenty-two patients were on peritoneal dialysis therapy, 2 patients were on hemodialysis therapy at the time of KT, and 1 patient underwent preemptive KT. Eleven acute rejection episodes occurred in 8 patients. All episodes were completely reversed with treatments that included mainly methylprednisolone pulse therapy. Posttransplantation lymphoproliferative disorder occurred in 2 patients. Follow-up data showed that all grafts were functioning during a mean observation period of 41.1 months (range, 4 to 187 months). All persons providing primary support for patients were satisfied with the KT and believed that quality of life was improved in both transplant recipients and themselves. Conclusion: Results indicate that KT is not contraindicated in handicapped patients, but cannot determine which patients are unsuitable to undergo KT.

Influenza C virus (Inf. C) is one of pathogens of human respiratory tract infection and prevalent throughout the world at an early stage in life. However, Inf. C has been isolated only accidentally and there have been few reports on its clinical and epidemiological features. From November 1999 to March 2000, Inf. C was isolated from clinical specimens (throat swabs) of 4 pediataric patients with respiratory tract illness at Hiroshima Prefectural Hospital and was isolated in 4 peditaric patients at the other medical institutions in Hiroshima prefecture. There were no differences in clinical features including duration of illness, duration of fever, maximum body temperature between 4 patients with Inf. C infection and patients with influenza A (H1N1 and H3N2) and influenza B infection from 1992 to 2000. We investigated geographical distribution of patients with inf. C infection and analyzed for antigenic characteristics with a set of monoclonal antibodies against hemagglutinin-esterase glycoproteins. The data suggested that at least two antigenically different Inf. C prevalented in a region during winter from 1999 to 2000.

Severe hypertension (HTN) and acute kidney injury frequently associated with atypical hemolytic uremic syndrome (aHUS) were refractory to various therapies in the pre-eculizumab era. Here we report the case of a 4-month-old boy who developed aHUS presenting with undetectable C3 protein, no predisposing mutations in complement factors, and no antibodies against factor H.Repeated plasma infusions and nine sessions of plasmapheresis were ineffective. The patient initially required continuous hemodiafiltration and thereafter peritoneal dialysis. Despite vigorous antihypertensive treatment and improved fluid overload with dialysis, HTN persisted. His low C3 level (20 mg/dl) suggested unrestricted complement activation. Therefore, based on the suspicion of unrestricted complement cascade in the pathogenesis, treatment with eculizumab, a human anti-C5 monoclonal antibody, was initiated with the aim of controlling disease activity.Eculizumab therapy resulted in the control of severe HTN and cessation of peritoneal dialysis.This infant with HTN and acute kidney injury associated with aHUS was treated successfully with eculizumab.

We report a 28-day-old female infant with pertussis presenting as severe acute bronchiolitis with cyanosis. On admission, the patient's symptoms were similar to those of acute bronchiolitis. However, occasional apneic episodes with cyanosis and peripheral lymphocytosis suggested neonatal pertussis and prompted us to examine the presence of Bordetella pertussis using loop-mediated isothermal amplification (LAMP) based on the insertion sequence IS481. LAMP of the nasopharyngeal and intratracheal aspirates was positive for B. pertussis and a diagnosis of neonatal pertussis was made. As the clinical features of pertussis in neonates and early infancy are not characteristic, LAMP is a useful tool for rapid diagnosis of B. pertussis infection.

AIM To evaluate the efficacy of single-dose oral mizoribine (MZB) pulse therapy given twice weekly for frequently relapsing steroid-dependent nephrotic syndrome (FR-SDNS). METHODS The subjects were 8 patients with FR-SDNS with a median age of 6.9 years old (range 3.1 - 18.0 y). The study was performed as a Phase II trial. The MZB dose was adjusted to achieve a peak blood level of 3 - 5 μg/ml (3.9 - 15.9 mg/kg/d, maximum dose: 750 mg) using a single dose given twice weekly before a meal. The therapeutic benefits of MZB pulse therapy were assessed based on a comparison of the incidence of relapse and the required daily dosage of prednisolone (PSL) in the 12 months prior to and following therapy. RESULTS The incidence of relapse after therapy was significantly lower than that before therapy (2.5 ± 1.4 vs. 4.3 ± 0.5, p < 0.01) and the required daily dosage of prednisolone (PSL) after therapy was lower than that before therapy (0.48 ± 0.23 vs. 0.52 ± 0.32 mg/kg/d, not significant). However, this therapy was not effective for 3 out of 4 patients treated with cyclosporine. During follow-up, discontinuation of PSL was possible in 4 of 5 patients who showed a decreased rate of relapse after therapy. The peak blood concentration of MZB in these patients was significantly higher than that in 3 patients who did not show a decreased rate of relapse (3.95 ± 0.11 vs. 3.05 ± 0.21 μg/ml, p < 0.01). No adverse effects were observed in any patients. CONCLUSION Our results show that single-dose oral MZB pulse therapy is effective in decreasing the frequency of relapse in some pediatric patients with FR-SDNS. A peak concentration of MZB of ~3.8 - 4.0 μg/ ml may be required for FR-SDNS therapy.

The morphology and antigenic property of elementary bodies (EBs) of new Chlamydia pneumoniae YK-41 strain isolated in Hiroshima, Japan, were compared with those of C. pneumoniae strains TW-183 and AR-39, C. trachomatis L2/434/Bu strain and C. psittaci Cal 10 and Budgerigar-1 strains by SDS-PAGE and immunoblotting techniques. In spite of a clear difference in EB morphology between the YK-41 and the other C. pneumoniae strains used, protein profile of the YK-41 strain in SDS-PAGE was similar to that of the other strains. However, some quantitative difference in 200 and 98 kDa peptides and a faint difference in SDS-PAGE pattern was also observed in the molecular masses from 42 to 50 kDa. Immunoblot analysis with the patient serum at the convalescent stage revealed the presence of genus-specific and species-specific antigens in YK-41 EBs: i. e., the major outer membrane protein and 73 kDa peptides were genus-specific and the peptides of 43, 46, 53, 60 and 98 kDa appeared to be C. pneumoniae-specific.

A 78-year-old woman was admitted to our hospital complaining of persistent abdominal pain and diarrhea. Computed tomography (CT) and colonoscopy (CF)revealed a huge ascending colon tumor, invading the descending part of the duodenum. The patient was treated preoperatively with a combination of S-1 plus CPT-11 (S-1 80 mg/body day 1-29, CPT- 11 100 mg/body day 1, 8, 15 and 22). No serious side effect was observed except low-grade fever and grade 2 appetite loss and diarrhea. Tumor reduction was significant on the preoperative CT and CF, with the invasion to the duodenum obscured. Right hemicolectomy with wedge resection of the duodenum was performed. Resected specimen revealed residual tumor in a small area of the submucosal to proper muscular layer of the contracted ascending colon, without pathological invasion to the duodenum. No nodal metastasis was observed. The patient was administered UFT (300 mg daily)postoperatively for two years and is still alive and free of disease after three years and ten months since the operation.

We studied changes in the drug resistance of 606 strains of Haemophilus influenzae (H. influenzae) and 502 strains of Streptococcus pneumoniae (S. pneumoniae) isolated from our patients between 1997 and 2006. The incidence of beta-lactamase nonproducing ampicillin-susceptible H. influenzae (BLNAS) in 1997-1998 and 1999-2000 was 72.0 and 69.6%, respectively. In 2005-2006, the incidence of BLNAS decreased to 31.0%, while that of beta-lactamase nonproducing ampicillin-resistant H. influenzae (BLNAR) and intermediate-resistant H. influenzae increased to 65.5%. Remarkably early development of BLNAR and intermediate-resistant H. influenzae was found in patients younger than 3 years, as compared to patients older than 3 years. The proportion of penicillin-susceptible S. pneumoniae (PSSP) in 1999-2000 was 18.4%. In 2005-2006, the proportions of penicillin-resistant S. pneumoniae (PRSP) and penicillin-intermediate S. pneumoniae (PISP) were lower, while that of PSSP increased to 38.2%. An early increase in the proportion of PSSP was found in patients older than 3 years, as compared to patients younger than 3 years. The difference between age groups may be attributed to entrance into nursery school, frequent administration of antibiotics, and the immature immunological state of patients younger than 3 years. Therefore, changes in the drug resistance of H. influenzae and S. pneumoniae should be investigated separately, depending on the age of the patients. The minimum inhibitory concentrations of antibiotics, including cefditoren and cefcapene, against BLNAR and PRSP did not increase. The marked increase in intermediate-resistant H. influenzae and BLNAR mandates a re-evaluation of the directions for antibacterial agents.

Recurrent FSGS is a major challenge in the field of nephrology. To clarify the role of NPHS2 defects in the pathogenesis of FSGS recurrence, we sequenced all eight exons of NPHS2 in 11 Japanese pediatric FSGS patients with or without post-transplant recurrence. All patients had biopsy-proven primary FSGS, had no family history of renal diseases or consanguinity, were steroid-resistant, and received living-related renal transplantation. The mean age at onset was 5.0 +/- 3.1 yr and mean age at renal transplantation was 10.4 +/- 4.1 yr. Mutational analysis of NPHS2 was performed using polymerase chain reaction and direct sequencing. We found a synonymous T/C polymorphism at alanine 318 (GCC to GCT) in seven of 11 patients but no other causative NPHS2 mutations. FSGS recurred immediately after transplant in seven patients, while the remaining four patients had no recurrence for 3.2-5.8 yr. There were no differences between recurrent and non-recurrent patients in the onset age and the interval from onset to ESRD. In conclusion, we detected no causative NPHS2 mutations in Japanese pediatric FSGS patients with or without post-transplant recurrence. Further studies on the involvement of other genes are required to better understand recurrent FSGS.

Herein is presented the case of an esophageal pleomorphic giant cell carcinoma combined with small cell carcinoma (SCC). The patient, a 77-year-old man, initially presented with dysphagia and hoarseness, and endoscopy indicated a large esophageal tumor. Despite chemoradiation therapy, the patient died from widespread local extension of the tumor and distant metastases approximately 8 months after onset of the symptoms. Histologically, the primary tumor was composed of pleomorphic tumor components, SCC components, and a tiny focus of squamous cell carcinoma. The pleomorphic tumor cells, consisting of solid sheets of poorly cohesive epithelioid cells and numerous multinucleated giant cells with abundant eosinophilic cytoplasm, were immunohistochemically positive for vimentin and desmin, with scattered positivity for epithelial membrane antigen (EMA) and neuron-specific enolase (NSE), but negative for myoglobin. These findings were histopathologically compatible with pleomorphic giant cell carcinoma occurring at other sites such as the lung. SCC cells, morphologically similar to their pulmonary counterpart, were positive for EMA and some neuroendocrine markers such as chromogranin A and NSE, and occasionally positive for vimentin and desmin. Esophageal pleomorphic giant cell carcinoma can occur in close association with SCC, and should be included in the differential diagnosis of esophageal tumors showing pleomorphism.

Tumor regression is used widely as a measure of tumor response following radiation therapy or chemoradiation therapy (CRT). In cases of esophageal cancer, a different pattern of tumor shrinkage is often observed between primary tumors and metastatic lymph nodes (MLNs). Regression of MLNs surrounded by normal tissue may be a more direct measure of the response to CRT than regression of a primary tumor as exfoliative mechanical clearance does not participate in shrinkage of MLNs. In this study we evaluated the significance of the reduction rate (RR) of MLNs as a prognostic factor in esophageal cancer patients treated with neoadjuvant CRT. Forty-two patients with marked MLNs were selected from 93 patients with esophageal carcinoma who had received neoadjuvant CRT. The RRs of the primary tumor and the MLNs were calculated from computed tomography scans. In 20 patients, surgical resection was carried out following CRT. Univariate analysis was used to determine which of the following variables were related to survival: size of the primary tumor and MLNs; RRs of both lesions; degree of lymph node (LN) metastasis; clinical stage; and surgical resection. Multivariate analysis was then performed to assess the prognostic relevance of each variable. The primary tumor was larger than the MLNs in 69% of patients before CRT and in 40% of patients after CRT. In 79% of the patients, the RR of the primary tumor was greater than the RR of the MLNs. The results of the univariate analyses showed that a high RR of the MLNs and surgical resection after CRT were associated with significantly improved survival. The multivariate analysis demonstrated that the RR of MLNs had the strongest influence on survival. The RR of LN metastasis should be evaluated as an important prognostic predictor in patients with marked LN metastasis of esophageal cancer treated with CRT.

Influenza C virus (Inf. C) is one of pathogens of human respiratory tract infection and prevalent throughout the world at an early stage in life. However, Inf. C has been isolated only accidentally and there have been few reports on its clinical and epidemiological features. From November 1999 to March 2000, Inf. C was isolated from clinical specimens (throat swabs) of 4 pediataric patients with respiratory tract illness at Hiroshima Prefectural Hospital and was isolated in 4 peditaric patients at the other medical institutions in Hiroshima prefecture. There were no differences in clinical features including duration of illness, duration of fever, maximum body temperature between 4 patients with Inf. C infection and patients with influenza A (H1N1 and H3N2) and influenza B infection from 1992 to 2000. We investigated geographical distribution of patients with inf. C infection and analyzed for antigenic characteristics with a set of monoclonal antibodies against hemagglutinin-esterase glycoproteins. The data suggested that at least two antigenically different Inf. C prevalented in a region during winter from 1999 to 2000.

BACKGROUND A retrospective investigation was conducted to define the clinical features of exercise-induced acute renal failure (ARF) associated with renal hypouricaemia with the aim of clarifying further the clinical features of the disease entity. METHODS A questionnaire was mailed to 43 institutions in Japan that had experienced case(s) of exercise-induced ARF associated with renal hypouricaemia. Fifty-four patients (48 males and six females) were identified from 38 institutions. RESULTS Median age at the first episode of ARF was 17 years (range 11-46). The maximal serum uric acid and creatinine levels were 4.40+/-2.49 (range 0.4-13.3) and 5.45+/-3.33 mg/dl (range 1.10-17.7), respectively. The serum uric acid level after recovery was 0.70+/-0.25 mg/dl (range 0.1-1.4). The short-term prognosis seemed to be good and histological findings in 28 patients showed minimal change or acute tubular necrosis except for one patient with chronic lesions. ARF episodes occurred predominantly in September, October and May, mostly after strenuous exercise such as a short-distance race. The first symptoms were nausea/vomiting in 51 episodes, loin pain in 35, abdominal pain in 22, general fatigue in 16 and low-grade fever in seven. Thirteen patients (24.1%) experienced recurrent ARF at various intervals. Univariate and multivariate analyses failed to demonstrate any risk factor of ARF recurrence, although no female patients experienced ARF recurrence. CONCLUSIONS The reason for the heterogeneity in ARF associated with renal hypouricaemia remains unknown. Further studies, especially on molecular mechanisms, are required to establish the best guidance against ARF recurrence.

Human metapneumovirus (hMPV) was newly discovered as a pathogen in 2001 and is thought to be associated with respiratory disease. To elucidate the prevalence and clinical significance of hMPV among children, we investigated the positive cases of hMPV-RNA by reverse transcription-polymerase chain reaction (RT-PCR) in their nasopharyngeal specimens collected from January to August 2003 in Hiroshima Prefecture, Japan. Our prospective study revealed 77 hMPV-positive cases among 377 children with acute respiratory diseases. Clinical diagnoses of 77 hMPV-positive cases were as follows; bronchitis (33.8%), pneumonia (24.7%), acute respiratory illness (19.5%), asthmatic bronchitis (11.7%) and bronchiolitis (5.2%). The most common symptoms were cough (97.4%), high fever (94.8%) and rhinorrhea (76.6%). Most of the hMPV-positive cases were identified in the spring (between March and May), indicating the presence of an epidemic of hMPV infection in Hiroshima Prefecture. Phylogenetic analysis of the amplified F gene of hMPV isolates revealed that hMPV strains were divided into two genotypes and that their simultaneous circulation occurred within the same epidemic area of Hiroshima Prefecture.

Two siblings with allergic purpura after Salmonella O9 infection were reported. A girl (patient 1) aged 4 years and 4 months started to have knee joint pain and abdominal pain followed by purpura of the lower extremities and was referred to us for treatment of allergic purpura. She had contracted enterocolitis one month before visiting our hospital and Salmonella enteritidis was identified. During the course of the illness she had nephritis associated with allergic purpura. However, she made a favorable progress and proteinuria and hematuria disappeared within 6 months. A boy (an elder brother of patient 1) aged 6 years was admitted to our hospital because of the allergic purpura. He similarly had contracted Salmonella enterocolitis. He had severe gastro-intestinal symptoms including abdominal pain, vomiting and bloody stool, which rapidly subsided after initiation of treatment with intravenous hyperalimentation combined with prednisolone. It is possible that allergic purpura in our patients was closely associated with Salmonella enteritidis infection. Further accumulation of cases is a requisite to clarify an association of Salmonella enteritidis infection with allergic purpura and pathogenesis of allergic purpura.

A 14-year-old girl with rapidly progressive glomerulonephritis was transferred to our hospital because of acute renal failure. A diagnosis of Wegener granulomatosis was made according to the symptom triad of a renal biopsy demonstrating crescentic glomerulonephritis, severe sinusitis, and serological findings of raised proteinase 3 anti-neutrophil cytoplasmic antibody level. In spite of combination therapy with methylprednisolone, cyclophosphamide, and plasma exchange, her renal function gradually deteriorated. Thereafter, she suffered a severe headache and generalized seizures. Brain computed tomography (CT) scan revealed bilateral low-density areas in the parieto-occipital lobes. Magnetic resonance imaging (MRI) disclosed a high-intensity area on T2-weighted images and a low-signal intensity area on T1-weighted images in the same lesion. Follow-up brain CT scan 3 weeks and MRI 2 months after the first studies showed complete resolution of the abnormal lesions, which indicated reversible posterior leukoencephalopathy syndrome. In addition to renal failure, hypertension, and cyclophoshamide, the primary disease may have played a role in the development of this uncommon syndrome in our patient.

A 14 year old boy with chronic mucocutaneous candidiasis and persistent pulmonary infection caused by Haemophilus influenzae and Streptococcus pneumoniae is reported. Initial bacterial culture studies showed H. influenzae type B and S. pneumoniae as causative agents. H. influenzae type D was constantly isolated from the patient's sputum. Abnormally low levels of serum immunoglobulin G2 (IgG2) found in the patient may have contributed to the pulmonary infection and H. influenzae type D may be an important causative agent in immunodeficient patients.

A 15-year-old boy with chronic renal failure secondary to Alport's syndrome underwent living-related renal transplantation from his 48-year-old father. His primary immunosuppressive regimen was composed of tacrolimus, mizolibine, and methylprednisolone. The postoperative course was satisfactory with one episode of mild acute rejection, treated successfully with methylprednisolone pulse therapy. Two months later, hypercalcemia (11.8-13.2 mg/dl) and hypophosphatemia (2.5-3.0 mg/dl) were noted without any bone symptoms. The serum intact-parathyroid hormone (PTH) and serum alkaline phosphatase levels were 240 pg/ml and 2483 IU/l, respectively. Ultrasound studies revealed enlargement of the two parathyroid glands. Under the diagnosis of tertiary hyperparathyroidism, he underwent percutaneous ethanol injection (PEIT) into the left parathyroid gland. Although levels of serum calcium and phosphorus returned to normal ranges and the intact PTH level decreased to 95 pg/ml with the three injections, another injection was needed to normalize recurrent hypercalcemia 2 months later. The patient experienced only transient mild dysphonia and local pain after PEIT. Although PEIT is believed less effective than parathyroidectomy, it has some advantages such as applicability to high-risk patients, repeatability of treatment, low incidence and severity of side effects.

We evaluated a 1-year course of a newly developed immunosuppressant, mizoribine (at a dosage of 3 mg/kg body weight per day), in nine children with steroid-dependent nephrotic syndrome. Steroid treatment could be discontinued in two patients and the maintenance dosage of steroid could be reduced to less than half of that given before mizoribine therapy in a third. There were no beneficial effects in the remaining six patients. No adverse effects of mizoribine were observed during the course of therapy.

Chlamydia was isolated from the throat of a 15-year-old male patient with acute bronchitis. The Chlamydia isolate, YK-41, was stained with FITC-conjugated monoclonal antibodies specific to C. pneumoniae and the genus Chlamydia, whereas staining of monoclonal antibody specific to C. trachomatis was negative. These results indicated that the strain YK-41 could be identified as C. pneumoniae. Serum IgM antibody against C. pneumoniae was detected in high titer in the patient in the acute phase using the microimmunofluorescence (MIF) test, serum IgG antibody against C. pneumoniae demonstrated a fourfold antibody titer rise between acute and convalescent serum using MIF test. Thus, our patient almost certainly contracted acute bronchitis caused by C. pneumoniae.

We studied the effect of phorbol myristate acetate (PMA) on endogenous leukotriene B4 (LTB4) metabolism of calcium ionophore A23187-stimulated human neutrophils. Preincubation of normal neutrophils with PMA significantly suppressed the recovery of endogenous LTB4 induced by A23187. PMA did not suppress the recovery of LTB4 produced by neutrophils from patients with chronic granulomatous disease (CGD), which is known to be defective in NADPH oxidase activation to produce reactive oxygen species (ROS). PMA inhibited the formation of omega-oxidation products of LTB4, but enhanced arachidonic acid release in normal and CGD neutrophils. Furthermore, 5-lipoxygenase activity of 10,000 x g supernatants from normal neutrophils pretreated with PMA was equivalent to that of the controls. Decrease in LTB4 recovery was not attributed to the suppression of the intracellular Ca2+ increase. Thus, it is suggested that reactive oxygen species (ROS) produced by PMA may directly affect endogenous LTB4 and convert it into metabolite(s) distinct from omega-oxidation products.

Exogenous adenine strongly inhibited mitogen-stimulated transformation, cytoplasmic immunoglobulin production, and natural killer activity of human mononuclear leukocytes at the high concentration of 1.0 mM. These inhibitions by adenine were not due to cytotoxicity, because the viability of cultured cells was not affected by adenine up to 1.0 mM. As the magnitude of inhibition by adenine of these in vitro immunological functions was similar in normal and adenine phosphoribosyltransferase-deficient cells, its inhibition was not mediated by corresponding nucleotides. Adenine at the concentration of 0.1 mM caused 50% inhibition of cytoplasmic immunoglobulin production without alternating cell proliferation or viability. This suggests that an appropriate concentration of adenine may inhibit the differentiation of B cells to plasma cells rather than affecting cell proliferation. Understanding the mechanisms of adenine inhibition may lead to new approaches for the regulation of immune responses.

Pituitary hyperplasia, microadenoma or an empty sella was detected in three children with primary hypothyroidism and three with Turner syndrome with the use of high resolution contrast-enhanced computed tomography (CT) with thin slices. Hyperplasia or microadenoma of the pituitary gland frequently occurs secondary to primary hypothyroidism and gonadal dysgenesis, and recognition of these results may eliminate unnecessary surgery in favor of hormone replacement therapy. High resolution contrast-enhanced CT, especially coronal CT, with thin slices is very helpful in demonstrating these pituitary abnormalities.

Undersulfation observed in the glycosaminoglycans synthesized by cultured skin fibroblasts from a Lowe's syndrome patient [Fukui, S. et al . (1981) J. Biol. Chem. 256, 10313–10318] was found to be caused by elevated degradation of 3′-phosphoadenosine 5′-phosphosulfate (PAPS). The enzyme involved in this degradation was then identified as an enzyme of nucleotide pyrophosphatase (EC 3.6.1.9) nature, cleaving the phosphosulfate linkage. The specific activities were 8 – 24 (mU/mg protein) in patients' fibroblasts, in contrast to 3 in normal and 5 – 14 in heterozygote cells. A possibility is discussed that the elevation of nucleotide pyrophosphatase activity is the primary genetic defect in Lowe's syndrome.

Glycosaminoglycan metabolism in cultured skin fibroblasts from a patient with Lowe's syndrome (oculocerebrorenal syndrome) was compared with that in normal fibroblasts. Cells were incubated with [3H]glucosamine and 35SO42-, and then the labeled glycosaminoglycans in the medium, trypsinate, and cell membrane fractions were analyzed by means of enzymatic and chemical degradations and by electrophoresis. Glycosaminoglycans, mostly chondroitin sulfates and dermatan sulfate, were markedly undersulfated in Lowe's syndrome. Undersulfation was most pronounced in the cell membrane fraction of cells which had been incubated at 0.03 mM sulfate concentration. Even at 0.52 mM or a higher sulfate concentration, undersulfation of chondroitin sulfates in the cell membrane fractions was significant. The undersulfation was the result of depressed sulfation rather than that of increased desulfation, as demonstrated by pulse-chase experiments using 35SO42-. Hyaluronate synthesis was not significantly impaired in the Lowe's syndrome fibroblasts. It was inferred, based on the results of the present study and those previously reported that the undersulfation of glycosaminoglycans is a consequence of a lower level of active sulfate (adenosine 3'-phosphate 5'-phosphosulfate) in the Lowe's syndrome fibroblasts, caused by an elevation of nucleotide pyrophosphatase activity degrading adenosine 3'-phosphate 5'-phosphosulfate.

We report a patient with low serum IgA levels and persistent pulmonary infection. In spite of the normal contents of serum IgG and IgM, the patient had a deficiency for plasma cell differentiation of all major classes of immunoglobulins (IgG, IgA and IgM). Cross culture systems between normal T or B cells and the patient's T or B cells showed a defect of both T and B cell function.

Zinc determinations were made in a 5 month-old female with the Chediak-Higashi syndrome. Zinc concentrations in plasma, erythrocytes, lymphocytes and granulocytes from the patient were significantly higher than those in healthy children of a similar age, and were higher than--or equal to--those of healthy adults. Lymphocyte zinc levels in the parents were significantly lower than those of healthy adults. Although the cause of the high zinc concentrations in these samples cannot be fully explained , abnormally high zinc levels may be partially responsible for impairment of some leukocyte functions in patients with CHS since zinc plays a central role in cellular metabolism.

On the initial examinations of a 17-year-old boy with acro-osteolysis syndrome, the levels of serum 25-hydroxycholecalciferol (25OHD) were low, whereas serum levels of 1,25-dihydroxycholecalciferol (1,25(OH)2D) were normal. Administration of 1 alpha-hydroxycholecalciferol (1OHD) failed to improve the osteoporosis, although the serum 25OHD level rose to normal. It is unlikely that impaired bone remodeling due to abnormal vitamin D-metabolism was a primary defect in our patient.