A clinical comparison between dedifferentiated low-grade osteosarcoma and conventional osteosarcoma.

AIMS: The purpose of this study was to clarify the clinical behaviour, prognosis, and optimum treatment of dedifferentiated low-grade osteosarcoma (DLOS) diagnosed based on molecular pathology. PATIENTS AND METHODS: We retrospectively reviewed 13 DLOS patients (six men, seven women; median age 32 years (interquartile range (IQR) 27 to 38)) diagnosed using the following criteria: the histological coexistence of low-grade and high-grade osteosarcoma components in the lesion, and positive immunohistochemistry of mouse double minute 2 homolog (MDM2) and cyclin-dependent kinase 4 (CDK4) associated with MDM2 amplification. These patients were then compared with 51 age-matched consecutive conventional osteosarcoma (COS) patients (33 men, 18 women; median age 25 years (IQR 20 to 38)) regarding their clinicopathological features. RESULTS: The five-year overall survival (OAS) rates in the DLOS and COS patients were 85.7% and 77.1% (p = 0.728), respectively, and the five-year progression-free survival (PFS) rates were 57.7% and 44.9% (p = 0.368), respectively. A total of 12 DLOS patients received chemotherapy largely according to regimens for COS. Among the nine cases with a histological evaluation after chemotherapy, eight showed a poor response, and seven of these had a necrosis rate of < 50%. One DLOS patient developed local recurrence and five developed distant metastases. CONCLUSION: Based on our study of 13 DLOS cases that were strictly defined by histological and molecular means, DLOS showed a poorer response to a standard chemotherapy regimen than COS, while the clinical outcomes were not markedly different. Cite this article: Bone Joint J 2019;101-B:745-752.

High titre of anti-Ascaris immunoglobulin E associated with bronchial asthma symptoms in 5-year-old rural Bangladeshi children.

BACKGROUND: Increasing interest has arisen whether helminthic infections protect against asthma and allergy. The prevalence of wheezing among Bangladeshi children is higher in rural areas where helminthic infectious burden is greater, which is contrary to the general assumption. OBJECTIVE: We therefore examined the association between Ascaris infection, serum level of anti-Ascaris IgE, which should be investigated differently from the infection, and wheezing in 5-year-old children from rural Bangladesh. METHODS: A total of 219 children who reported wheezing during the previous 12 months and 122 randomly selected age-matched individuals who had never experienced wheezing were tested for serum levels of total and specific Ascaris, Dermatophagoides pteronyssinus, alternaria and cockroach IgEs, and for intestinal helminth infection as well. RESULTS: Anti-Ascaris IgE levels were significantly and independently associated with current wheezing during the previous 12 months [odds ratio (OR) per log(e) increment is 1.31 (95% confidence interval (CI) 1.08-1.60), P=0.007], a history of at least four episodes of wheezing [OR per log(e) increment is 1.52 (95% CI 1.18-1.96), P=0.001], wheezing with sleep disturbances [OR per log(e) increment is 1.35 (95% CI 1.10-1.64), P=0.011] and wheezing with speech disturbances [OR per log(e) increment is 1.57 (95% CI 1.19-2.08), P=0.001]. These were adjusted for gender, pneumonia history, parental asthma, Trichuris infection, use of dry leaves as fuel and other specific IgE levels. The prevalence of Ascaris infection by the presence of wheezing was not significantly different (76% vs. 72%, respectively). CONCLUSION: We conclude that a high titre of anti-Ascaris IgE is associated with an increased risk of asthma symptoms among 5-year-old rural Bangladeshi children with a high helminthic infectious load.

Professional healthcare use for life-threatening obstetric conditions.

Obstetric complications are the major causes of death and disability in women of reproductive age. Our study aimed at investigating the use of professional healthcare when women in communities recognised possible life-threatening obstetric conditions (PLTCs). We conducted a survey in a Cambodian district with a population of 130,000. The subjects were women of reproductive age who had delivered babies during a 3-month period prior to the survey. We interviewed 980 women, and 141 (14.4%) of these had PLTCs. The utilisation rates of professional healthcare were 47% for prolonged labour; 42% for bleeding during the delivery and puerperal period; 33% for antenatal bleeding; 25% for convulsion; and 23% for postpartum high fever. A logistic regression analysis revealed that education, geographic accessibility and parity were significant determinants of seeking healthcare. Two additional determinants, namely, economic affluence and antenatal care attendance, were identified in the socioeconomic status (SES) and obstetric models.

Recurrent Membranous Nephropathy After Kidney Transplantation Associated With Phospholipase A2 Receptor and Successfully Treated With Rituximab: A Case Report.

Primary membranous nephropathy (MN) is an organ-specific autoimmune disease mainly caused by autoantibodies acting against the podocyte antigen M-type phospholipase A2 receptor 1 (PLA2R). Herein we present the clinical and histologic findings, including PLA2R staining, of early recurrent MN after kidney transplantation that was successfully treated with rituximab. A 60-year-old Japanese man had end-stage renal failure due to steroid-resistant primary MN and underwent ABO-incompatible living donor kidney transplantation. At 1 month after transplantation, a protocol biopsy revealed positive granular staining of IgG, C4d, and PLA2R on glomerular capillaries (GCs) without any abnormalities on light microscopy (LM). Although the patient had low-level proteinuria, recurrent MN was suspected based on the positive PLA2R staining; he was treated with an angiotensin receptor blocker and a single dose of 200 mg rituximab. However, proteinuria gradually increased to 877 mg/d. At 21 months after transplantation, a graft biopsy revealed spikes along the outer aspects of GC on LM, with stronger staining for PLA2R than that at 1 month after transplantation. A single dose of 500 mg rituximab was added, which effectively reduced proteinuria, and clinical remission continued until 3 years after transplantation. The latest graft biopsy showed reduced staining of PLA2R. The disease activity and therapeutic effect were well-reflected in the intensity of PLA2R staining. An approach intending an early diagnosis by protocol biopsy using PLA2R immunostaining is made and early treatment with rituximab will help reduce the risk of kidney graft loss due to recurrent primary MN.

Magazine information on safety belt use for pregnant women and young children.

To assess the information on safety belt use for pregnant women and infants in maternity and baby magazines, we reviewed 2003 issues of the three top-selling monthly baby and maternity magazines. Articles on safety belt use during pregnancy and child safety seat (CSS) use for infants, and advertisements of the CSS, automobiles, or CSS-related products were examined for their informational content. Of the 9418 pages in the maternity magazines, 46 pages were on infants, 16 pages on pregnant women and 162 pages displayed advertisements. Of the 9750 pages in the baby magazines, 34 pages of articles addressed CSS use; no articles addressed the issue of pregnant women; 83 pages were advertisements. Although the magazines showed accurate information in general; its amount was not sufficient, and little specific information on appropriate use and selection of a CSS was seen. Some information was misleading and even incorrect: specifically related to when to start using a forward-facing seat, what products are attachable to the CSS, and the reuse of a CSS. Greater amounts and accuracy of safety information in these magazines would help pregnant women and parents acquire important safety knowledge that healthcare providers are falling short of providing in Japan.

Living Kidney Donation From a Donor With Pulmonary Sarcoidosis: A Case Report and Review of the Literature.

BACKGROUND: Sarcoidosis is a chronic systemic disease that is characterized by the formation of noncaseating granuloma and whose etiology is unclear. It is unclear whether patients with sarcoidosis are suitable organ donors. CASE: We treated a 56-year-old woman with pulmonary sarcoidosis who donated her kidney. She was previously in good health and was diagnosed with pulmonary sarcoidosis during her preoperative examination. Because she presented with no symptoms and was otherwise in good condition, donor nephrectomy was performed. RESULTS: Baseline biopsy examination showed no evidence of sarcoidosis. One year after transplantation, both the donor and the recipient had not developed kidney dysfunction or recurrence of sarcoidosis. CONCLUSION: This is a rare case in which a patient with pulmonary sarcoidosis donated a kidney for transplantation, and both the recipient and the donor were clinically healthy. A patient with sarcoidosis and no kidney lesion can donate a living kidney, because transplantation appears to be safe for both the recipient and the donor.

Utility of the Japanese Glomerular Filtration Rate Equation in Estimating Glomerular Filtration Rate of Donor Kidney.

BACKGROUND: An equation for the estimated glomerular filtration rate (eGFR) is generally used for evaluating renal function in Japan. OBJECTIVE: To assess the accuracy of the preoperative eGFR for estimating kidney donors' measured glomerular filtration rate (mGFR). METHODS: Between April 2009 and August 2014, 91 Japanese living kidney donors were included in this study. The eGFR was calculated as follows: eGFR = 194 × serum creatinine(-1.094) × Age(-0.287) (and × 0.739 for women), and the mGFR was evaluated using inulin clearance. The preoperative eGFR was then compared with the mGFR. RESULTS: Patients included 27 men and 64 women with a mean age of 56.8 ± 9.5 years (range, 36-79 years), mean body surface area of 1.56 ± 0.14 m(2) (range 1.27-1.92 m(2)), mean body mass index of 22.3 ± 2.3 kg/m(2) (range 14.0-27.0 kg/m(2)), and mean serum creatinine level of 0.66 ± 0.14 mg/dL (range 0.39-0.97 mg/dL). The mean eGFR was 81.3 ± 14.2 mL/min/1.73 m(2) (range 45.5-125.9 mL/min/1.73 m(2)), and the mean mGFR was 89.0 ± 15.5 mL/min/1.73 m(2) (range 45.4-130.7 mL/min/1.73 m(2)). The eGFR was significantly lower than the mGFR (P < .001). The correlation coefficient for the relationship between the eGFR and mGFR values was 0.503, and the mean difference between the 2 values was -7.8 (8.7%). CONCLUSIONS: Although the eGFR correlated with the mGFR, the eGFR values did not accurately estimate the mGFR in living kidney donors. Therefore, it is necessary to evaluate the mGFR, especially in marginal kidney donors.

Immunoglobulin A Nephropathy in a Living Kidney Donor Diagnosed and Treated After Transplantation: A Case Report.

OBJECTIVE: We report the clinical course and pathologic findings of a kidney transplant donor who was diagnosed with immunoglobulin A (IgA) nephropathy by means of preimplantation biopsy and was later treated with methylprednisolone and tonsillectomy. CASE REPORT: The patient was a 57-year-old woman who met the criteria for kidney donation and was accepted as a donor. Donor nephrectomy was performed, and the preimplantation biopsy revealed that the donor had IgA nephropathy. One month after the nephrectomy, the donor's laboratory findings indicated proteinuria and hematuria. Because these findings indicated active IgA nephropathy, we decided to perform tonsillectomy and methylprednisolone pulse therapy. Soon after these treatments, the patient's proteinuria and hematuria were no longer observed. CONCLUSIONS: Subclinical IgA nephropathy can be incidentally found on preimplantation biopsies of living kidney donors. As demonstrated in this case, IgA nephropathy can become exacerbated and requires therapeutic intervention after kidney donation. Informed consent and careful observation should be used before and after transplantation, even for donors who have been determined to be eligible for kidney donation.

Preemptive Living Donor Kidney Transplantation and Kidney Function at the Initial Hospital Visit: A Single-Center Case-Control Study.

BACKGROUND: Studies have revealed that patients who undergo preemptive kidney transplantation (PKT) have favorable prognoses compared with those who undergo kidney transplantation after the initiation of dialysis. The number of PKT cases performed worldwide has been increasing. The goal of this study was to determine the clinical characteristics of patients who may successfully receive PKT. METHODS: A single-center, case-control study was conducted to determine the clinical factors that lead to referral for PKT. RESULTS: Between April 1, 2009, and August 1, 2015, a total of 118 patients underwent living donor kidney transplantation. Thirty of these patients had not undergone dialysis before their initial visit to the study hospital. Of these, 20 received kidney transplantation before and after dialysis initiation, respectively (group PKT+, successful PKT; group PKT-, failed PKT). The baseline characteristics at the primary visit were compared between groups. The median duration from the first visit to the study institution to PKT was 5.6 ± 0.7 months. Serum creatinine (Cr) levels differed significantly between groups (PKT+ vs PKT-, 6.0 ± 0.3 mg/dL vs 7.5 ± 0.5 mg/dL; P = .03). The receiver-operating characteristic curves revealed that a serum Cr level >5.7 mg/dL at the initial visit to the unit was a cutoff point for predicting the success of PKT (area under the curve, 0.721; P = .02). CONCLUSIONS: Our results indicate that PKT should be performed within ∼6 months of the initial visit to the transplant center. Serum Cr levels <5.7 mg/dL predict successful PKT.

Traditional healers' roles on eye care services in Nepal.

AIM: To evaluate the traditional healer (TH) training programme carried out by Nepal Netra Jyoti Sangh, a non-governmental organisation in Nepal, by measuring the changes in knowledge and practices of trained THs in providing primary eye care services. METHODS: 103 trained THs practising in six districts of Nepal were interviewed with a semistructured questionnaire. Their knowledge about various illnesses and eye care practices were compared before and after the training. RESULTS: A significant change in the number of THs with accurate perceived knowledge about trachoma (28.2% v 70.9%, p<0.0001) and cataract (54.4% v 94.2%, p<0.0001) was found after the training. In total, 98 (95%) THs stopped using traditional eye medicines after receiving the training (p<0.0001). The referral practices of THs improved significantly after the training (15% v 100%, p<0.0001). After the training, 95% of the THs used an eye care kit to treat patients with red eyes and simple ocular trauma. CONCLUSION: The findings show that a TH training programme on primary eye care services convinced traditional healers to stop the use of traditional eye medicines and improve referral practices in Nepal.

Exploratory study on psychosocial impact of the severe acute respiratory syndrome (SARS) outbreak on Chinese students living in Japan.

The aim of this study is to explore the impact of the 2003 SARS outbreak on Chinese students living in Japan. A cross-sectional study was conducted using a semi-structured questionnaire. The participants were recruited at multiple locations at the University of Tokyo, Japan. The results showed approximately 60% (96/161) of the respondents felt an impact of SARS on college life; they had experienced SARS-related fear, worry, depression as well as social discrimination and had taken SARS prevention measures for daily protection in Japan during the epidemic. The magnitude of the impact was associated with socio-demographic factors, including their age, specialty, area of previous residence in China and length of stay in Japan. The findings suggest that the SARS outbreak had a psychosocial impact on the Chinese students living in Japan, even though none of them had SARS. Social support tailored for these foreign students should be provided during such a disease outbreak.

Nutritional and mental health status of Afghan refugee children in Peshawar, Pakistan: a descriptive study.

The study sought to ascertain and describe the physical and mental health states of Afghan refugee children after the terrorist attack on September 11, 2001 in the US and the aerial bombing of Afghanistan that followed. A cross-sectional survey was carried out in four refugee camps in Peshawar, Pakistan from February to March 2002, and comparisons among camps were made. A total of 70 males (mean age SD = 9.81 +/- 1.98 years old) and 30 females (7.94 +/- 2.07) answered a self-developed questionnaire on demographic data, traumatic events experience, living environment in the camps, and physical and mental health, through interviews. Anthropometric measures were measured and physical symptoms including anaemia and edema were assessed. Severe malnutrition was not shown and there were no significant differences in most nutritional and physical states among the camps. Nevertheless, in the newer camps more children experienced war related traumatic events. Mental symptoms were prevalent in all camps, though the characteristics of the symptoms differed among the camps.

Plasma Cell-Rich Rejection After Kidney Transplantation and the Role of Donor-Specific Antibodies: A Case Report and Review of the Literature.

OBJECTIVE: We report a case of the clinical course and pathologic findings for a kidney transplant recipient with plasma cell-rich rejection (PCRR) accompanied by antibody-mediated rejection (ABMR). METHODS: A 29-year-old man with end-stage renal disease caused by lupus nephritis received an ABO-compatible living kidney transplant. RESULTS: Eighteen months after transplantation, the patient presented with proteinuria and increased serum creatinine. An episode biopsy revealed severe tubulointerstitial infiltration with plasma cells accompanied by peritubular capillaritis and positive findings on immunofluorescent C4d staining. Donor-specific antibodies were positive for DR52, and the patient was subsequently diagnosed with PCRR accompanied by ABMR. Treatment was initiated with high-dose steroids, intravenous immunoglobulin, gusperimus hydrochloride, muronmonab antibody CD3, and rituximab. However, ABMR persisted and allograft failure developed 20 months after onset. CONCLUSIONS: We argue that PCRR accompanied by ABMR is a subtype of PCRR that can progress to allograft failure owing to persistent ABMR.

Spontaneous regression of a cerebral arteriovenous malformation. Report of a case and review of the literature.

A cerebral arteriovenous malformation (AVM) spontaneously and completely disappeared on subsequent angiography. Computed tomography revealed a very similar picture to that of angiographically occult AVM, which was histologically thrombotic. Reviewing the literature, we suggest that in many cases the important factor related to regression of AVM is a previous bleeding episode.

Haplotype-phenotype correlation in Fukuyama congenital muscular dystrophy.

In typical Fukuyama congenital muscular dystrophy (FCMD), peak motor function is usually only unassisted sitting or sliding on the buttocks, though a few patients are able to walk at some point. However, a few patients have a severe phenotype and never acquire head control. In addition, it is clinically difficult to differentiate this severe FCMD from Walker-Warburg syndrome (WWS) or from muscle-eye-brain disease (MEBD). In order to establish a genotype-phenotype correlation, we performed haplotype analysis using microsatellite markers closest to the FCMD gene (FCMD) in 56 Japanese FCMD families, including 35 families whose children were diagnosed as FCMD with the typical phenotype, 12 families with a mild phenotype, and 9 families with a severe phenotype. Of the 12 propositi with the mild phenotype, 8 could walk and the other 4 could stand with support; 10 cases were homozygous for the ancestral founder (A-F) haplotype whereas the other 2 were heterozygous for the haplotype. In the 9 severe cases, who had never acquired head control or the ability to sit without support, 3 had progressive hydrocephalus, 2 required a shunt operation, and 7 had ophthalmological abnormalities. Haplotype analysis showed that 8 of the 9 cases of the severe phenotype are heterozygous for the A-F haplotype, and the other one homozygous for the haplotype. We confirmed that at least one chromosome in each of the 56 FCMD patients has the A-F haplotype. The rate of heterozygosity for the A-F haplotypes was significantly higher in severe cases than in typical or mild cases (P < 0.005). Severe FCMD patients appeared to be compound heterozygotes for the founder mutation and another mutation. Thus, the present study yielded molecular genetic evidence of a broad clinical spectrum in FCMD.

Focal circumvention of blood-brain barrier with grafts of muscle, skin and autonomic ganglia.

The efficacy with which circulating horseradish peroxidase (HRP) spreads from transplants into the brain's interstitial spaces (IS), was assessed by 3 factors: graft type, site and age. Pieces of skeletal muscle, skin or entire superior cervical ganglion (SCG) were inserted into the IV ventricle (ventricular) or substance of the brain (parenchymal). The age of the grafts, i.e. the intervals after transplantation, were 1, 3, 6 and 12 months. Generally, HRP spread into the IS to about the same extent from ventricular muscle and skin autografts--1 mm, but less from parenchymal SCG allografts--0.5 mm. The spread from all grafts--ventricular and parenchymal--diminished with time. Exudation distance from muscle was the same as that from skin grafts for the first 6 months, but by 1 year, the penetration was significantly greater from muscle than from skin transplants. The flow of HRP was more extensive from parenchymal SCG grafts than from parenchymal muscle and skin grafts at 6 and 12 months. In some of the 6 and 12 month old parenchymal grafts of muscle and skin, no detectable HRP was extravasated. HRP consistently penetrated the brain more deeply from ventricular skin and muscle grafts than from parenchymal ones because more tissue mass survived in ventricular than in parenchymal autografts. Though care was taken not to damage the brain surface during ventricular insertion, there was a consistent, vigorous, collateral sprouting of, as yet unidentified, cranial nerves. These sprouts innervated muscle and skin autografts which, consequently, were able to survive for at least 1 year and contained vessels permeable to HRP. Allografts of muscle between inbred strains did not become innervated, survived for only 2 months and contained the central, barrier type of vessels, but not their intrinsic, permeable type. Thus, it is the muscle cell or its basal lamina within muscle grafts that determines the type of surviving vessel. In SCG allografts, even when all their ganglion cells had disappeared, leaving only connective tissue, Schwann cells and their basal lamina, the ganglion's capillaries survived and remained permeable to HRP. Therefore, the characteristics of the SCG vessels are determined by the Schwann cell-fibroblast milieu rather than the neuronal one.

Central nervous system involvement and generalized muscular atrophy in occipital horn syndrome: Ehlers-Danlos type IX. A first Japanese case.

Occipital horn syndrome (OHS, Ehlers-Danlos syndrome type IX) belongs to the category of the copper metabolism disorders and is at present being investigated biochemically as is Menkes' disease. Unlike Menkes' disease, most patients with OHS have mild submentality. We report a case of OHS with severe central nervous system involvement and muscular atrophy in a 34-year-old male. He had psychomotor retardation and seizures since early childhood and now presented severe mental retardation and generalized muscular atrophy in addition to characteristic facial appearance, hyperelasticity of the skin and joint subluxation. Laboratory investigations revealed a low serum copper and ceruloplasmin level as well as intestinal non-absorption of copper. Radiographic imaging showed occipital exostoses, bladder diverticula, tortuosity of the peripheral vein and osteoporosis of the skeletal bones. The activity of lysyl oxidase, a copper-enzyme involved in cross-link formation in collagen, was found to be decreased in a skin-biopsy specimen. Electron-microscopic investigation of a muscle biopsy showed irregularity of the myofibrillar network and accumulation of concentric laminated bodies in the subsarcolemmal regions.

Delayed expression of dystrophin on regenerating muscle from two siblings with Becker muscular dystrophy.

We present here a unique expression of dystrophin on biopsied muscle from 2 siblings with Becker muscular dystrophy (BMD). They had neither muscle weakness nor atrophy. Clustered dystrophin-deficient fibers were constituted to regenerating basophilic fibers (mainly type 2C fiber) based on histochemical stainings. We speculate that the developmental delay in the expression of dystrophin is a characteristic finding in regenerating fibers from asymptomatic and young BMD patients, such as the siblings in this report.

Electron microscopic study of the biopsied cardiac muscle in Duchenne muscular dystrophy.

Cardiac muscular biopsies were performed on 4 patients with Duchenne muscular dystrophy (DMD). None of the patients had cardiac symptoms and all of them exhibited normal electro- and echocardiographic findings. Electron microscopic examination of cardiac muscles from 4 patients with DMD disclosed proliferation of the mitochondria, changes in the cristae, abnormalities of the Z-bands, dilatation of the sarcoplasmic reticulum, deposition of glycogen, and changes in the nuclei. The most striking finding in these patients was that the residual bodies were increased and were observed mainly in the perinuclear region. These ultrastructural features suggest that an extreme exhaustion had already been present in myocardial tissue of the patients prior to the onset of cardiac symptoms.

Expanding intracerebral hematoma from pituitary adenoma: case report.

We report the case of a 53-year-old man presenting with a headache of sudden onset and blurred vision secondary to hemorrhage from a nonfunctioning pituitary adenoma, which had been treated 25 years previously by transcranial surgery and postoperative irradiation. The intratumoral and intracerebral hematoma expanded to three times its initial size because of a recurrent hemorrhage that occurred during a 2-day period while the patient awaited surgery. The mechanisms of hematoma expansion and the management strategy in such a case are discussed, and a review of the pertinent literature is presented.