Hemophagocytic syndrome after Kawasaki disease

Hemophagocytic syndrome (HPS) is a rare and life-threatening disease in which a generalized histiocytic proliferation results in hemophagocytosis and up-regulation of inflammatory cytokines. This syndrome has been associated with infections, malignancy, drugs and immunologic triggers such as Kawasaki disease (KD). We describe the clinical and laboratory features of two children with HPS after KD and review the three previously reported pediatric cases of recrudescence of HD leading to HPS.     

Endotoxemia and elevation of lipopolysaccharide-binding protein after hematopoietic stem cell transplantation

BACKGROUND: Hematopoietic stem cell transplantation (SCT) carries a significant risk of severe therapy-associated complications chief among which is acute graft vs.host disease (aGVHD). Animal models indicate that myeloablative chemotherapy compromises the mucosal barrier, thereby allowing translocation of intestinal flora-derived lipopolysaccharides (or endotoxin) that subsequently trigger aGVHD, but there are no comparable data in humans. Our aim was to gain insight into the potential role of endotoxin and endotoxin-induced acute phase proteins in children undergoing SCT. METHODS: Plasma concentrations of C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) were measured in 57 pediatric patients undergoing SCT. In addition plasma endotoxin levels were measured in 25 patients. RESULTS: The previously described rise in CRP was confirmed, and a marked elevation of LBP was observed that peaked at Day 7 (median value, 6.6 microg/ml; P < 0.03 for all pairwise comparisons). CRP and LBP values were significantly correlated (r = 0.77, P < 0.001). A significant but complex relationship was noted between LBP concentrations at Day 0 and severity of subsequent aGVHD (P = 0.02). Of the 25 patients assayed, 11 (44%) had detectable endotoxemia, including 4 who were endotoxin-positive at Day 0. CONCLUSIONS: The detection of endotoxemia coupled with marked elevations in LBP at Day 7 raises the possibility that inflammatory responses early after SCT may be driven in part by the entry of lipopolysaccharide into the bloodstream.     

Genetic alterations in primary cutaneous CD30+ anaplastic large cell lymphoma

Primary cutaneous CD30+ anaplastic large cell lymphoma (C-ALCL) represents a distinct clinical subtype of CD30+ anaplastic large cell lymphomas. The etiology and underlying molecular pathogenesis of C-ALCL remain unclear. This study aimed to investigate genetic changes in C-ALCL. Comparative genomic hybridization (CGH) analysis of 23 DNA samples from 15 C-ALCL cases identified chromosome imbalances (CI) in 10 samples from eight cases (43%). The mean number of CI per sample was 2.09 +/- 3.86, with gains (2.00 +/- 3.85) more common than losses (0.09 +/- 0.29). The most frequent CI were gains of 1/1p and 5 (50%) and 6, 7, 8/8p, and 19 (38%). Microarray-based CGH analysis of six DNA samples from five cases with CI revealed genomic imbalances (GI) in all of the cases studied. This included oncogene copy number gains of FGFR1 (8p11) in three cases, and NRAS (1p13.2), MYCN (2p24.1), RAF1 (3p25), CTSB (8p22), FES (15q26.1), and CBFA2 (21q22.3) in two cases. Real-time PCR analysis of nine DNA samples from eight cases with CI and GI detected amplifications of CTSB and RAF1 in seven cases (88%), REL (2p13p12) and JUNB (19p13.2) in six cases (75%), and MYCN and YES1 (18p11.3) in four cases (50%). Immunohistochemical staining of paraffin sections from six cases demonstrated expression of JUNB protein in five cases and BCL2 in three cases. These results reveal a consistent pattern of genetic alterations in C-ALCL and provide the molecular basis for further investigation of this disease.     

Oocyte maturation,follicle rupture and luteinization in human cryopreserved ovarian tissue following xenografting

BACKGROUND: Previous studies have demonstrated development of antral follicles in cryopreserved human ovarian tissue after autografting and xenografting, thus indicating successful preservation of follicular function. The study aim was to assess whether these follicles could also undergo periovulatory changes in response to hCG. METHODS: Ovarian tissue from three patients were dehydrated in propanediol (PROH)/sucrose and cryopreserved using the slow cooling/rapid thaw procedure. Thawed tissue was placed under the kidney capsule in immunodeficient mice. Following growth (>20 weeks) in the presence of gonadotrophin, hCG was administered and ovarian tissue examined histologically. RESULTS: Thirty-two antral follicles (diameter range 0.6 to 5 mm) were examined. Histological evidence of a response to hCG was evident in all follicles. Disruption of the concentric layers of mural granulosa and theca cells was apparent in all antral cavities. In 17 (53%) follicles the exterior follicular wall had reduced to a few cells thick, and in eight (25%) the wall had ruptured. Mucified oocyte-cumulus cell complexes were present in 32 follicles, 17 of which had begun to detach from the pedicle. Resumption of meiosis had occurred in over half the oocytes (five metaphase II and seven metaphase I oocytes, eight germinal vesicle breakdown). Two corpora lutea were also detected. CONCLUSIONS: Follicles cryopreserved within human ovarian tissue using the PROH procedure, can develop to the antral stage and undergo periovulatory changes following xenografting and exposure to a luteinizing stimulus.     

An Australian study of midwives' breast-feeding knowledge

OBJECTIVE: To investigate midwives' breast-feeding knowledge, assess associations between knowledge and role, and report on the validity and reliability of the Breast-feeding Knowledge Questionnaire for the Australian context. DESIGN: Postal questionnaire. SETTING: National Australia. PARTICIPANTS: Midwives (n=3500) who are members of the Australian College of Midwives Inc (ACMI). FINDINGS: A response rate of 31% (n=1105) was obtained. Respondents were knowledgeable of the benefits of breast feeding and common management issues. Key areas requiring attention included management of low milk supply, immunological value of human milk, and management of a breast abscess during breast feeding. Participants over the age of 30, possessing IBCLC qualifications; having personal breast-feeding experience of more than three months; and more clinical experience achieved higher knowledge scores. Role perceptions were positive with 90% of midwives reporting being confident and effective in meeting the needs of breast-feeding women in the early postnatal period. Midwives' role perception contributed 39% of the variance in general breast-feeding knowledge scores and was a significant predictor of participants' breast-feeding knowledge. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The level of basic breast-feeding knowledge of Australian midwives was adequate but there are deficits in key areas. Knowledge variations by midwives may contribute to conflicting advice experienced by breast-feeding women. Further research is needed to investigate in-depth breast-feeding knowledge, breast-feeding promotion practices, and associations between knowledge and practice.     

Vulvar hidradenitis suppurativa. Immunohistochemical evaluation of apocrine and eccrine involvement

OBJECTIVE: To evaluate the pathology of vulvar hidradenitis suppurativa (HS). STUDY DESIGN: A retrospective review of the histology of resections for vulvar HS was performed, and a battery of immunohistochemical stains was performed. They included markers of apocrine differentiation (GCDFP-15, CD15, lysozyme) and eccrine differentiation (GCDFP-15, S-100, CA-19.9, HMB45). RESULTS: Thirteen cases were available for review. Eccrine glands accounted for the majority of glands in all cases. Apocrine glands were not seen or were present only away from the area of active inflammation in 10 cases. In two cases, glands were totally destroyed in the areas of inflammation. Evidence of follicular obstruction was present in 11 of 13 cases. Severity of inflammation was variable, ranging from minimal, with burned-out disease, to severe. Fibrosis was variable but was greater with less inflammation, suggesting a later stage in disease evolution. Inflammation of the glands was often absent or minimal and seen only with associated poral occlusion. GCDFP-15 stained both apocrine and eccrine glands (only the dark cells). S-100 stained only the secretory (clear) cells of the eccrine glands. CD15 stained apocrine glands. Lysozyme stained apocrine glands, but this was not a consistent finding. CA19-9 gave inconsistent results in eccrine glands. HMB-45 was negative in all cases. CONCLUSION: Cases of vulvar HS showed a majority of eccrine glands in active areas. Apocrine glands, when present, were away from active inflammation. Inflammation and eventual destruction of glands appear to be a secondary part of the disease process. GCDFP-15 is a reliable marker for both apocrine differentiation and the dark cells of eccrine glands. S-100 is a reliable marker for the clear cells of eccrine glands. CD15 also was reliable for apocrine differentiation. Lysozyme showed weak apocrine staining. CA19-9 and HMB-45 were not reliable markers for apocrine or eccrine gland differentiation.     

Three-dimensional imaging of the inner ear by volume-rendered reconstructions of magnetic resonance data

OBJECTIVE: To evaluate 3-dimensional inner ear visualization by volume rendering of high-resolution magnetic resonance data in patients with clinically suspected inner ear abnormality. DESIGN: Prospective comparative study of different postprocessing techniques, based on blinded film readings. SETTING: Tertiary referral hospital. SUBJECTS: Fifty patients (17 females and 33 males) aged 1 to 77 years (average age, 42 years) with sensorineural hearing loss, vertigo, and/or tinnitus. INTERVENTION: Postprocessing of magnetic resonance data to inner ear reconstructions by the use of volume rendering as well as maximum-intensity projection; caloric testing by electronystagmography. MAIN OUTCOME MEASURES: Film was read blindly by 4 radiologists using a 5-point parameter scale for image quality and diagnostic value. The assessibility of inner ear subsegments was evaluated. The specificity of volume-rendered reconstructions for detecting semicircular canal obliterations was assessed in a subgroup of 9 patients by caloric testing. The time required for data postprocessing as well as film reading was recorded by means of a stopwatch. RESULTS: Volume-rendered inner ear reconstructions were superior in image quality (P<.001), diagnostic value (P<.001), subsegment inner ear assessment (P<.01 to P<.001), and film reading time (P<.001) compared with maximum-intensity projections. The data postprocessing time was comparable for both techniques. Caloric weakness was noted in all patients assessed by electronystagmography. CONCLUSION: Volume rendering is the postprocessing technique of choice for 3-dimensional inner ear visualization, performing better than maximum-intensity projections with respect to various parameters.