Tinidazole in treatment of amoebic liver abscess in children

Tinidazole as a single drug therapy given in a single dose daily for 5 or 3 days was put to rigorous test in malnourished children. Of 25 children with amoebic liver abscess, 23 were cured. The 2 remaining cases required surgical drainage followed by other amoebicides, one subsequently dying from complicating bronchopneumonia.     

Molecular internalization of a region of myelin basic protein

The conformation of myelin encephalitogenic or basic protein (BP) was investigated with a double-antibody radioimmunoassay by studying the reaction of BP or its fragments with antibodies produced in two rabbits against peptide 43-88 linked to rabbit serum albumin. Both antisera reacted well with peptide 43-88 but showed little or no reaction with BP. Absorption of these antisera with a BP-immunoadsorbent did not remove the antibody activity against peptide 43-88. Within the region of peptide 43- 88 it was shown that peptides 68-88 and 79-88 gave an equivalent or better reaction than peptide 43-88, whereas peptides 43-67 and 64-73 had very little reactivity. In the BP fragments containing region 43-88, peptide 1-88 showed the best reactivity, peptide 20-166 showed minimal reactivity, while peptide 1-115 showed none. These data document the internal position of at least a portion of peptide 43-88 and all of residues 79-88 in the BP molecule. The much greater reactivity of peptide 1-88 as compared to peptide 1-115 suggests that the region or a portion of the region of BP containing residues 89- 115 participates in the conformational alignment of BP restricting access to peptide 79-88. After absorption with BP, neither of the antisera prepared to peptide 43-88 reacted with PNS myelin in fixed tissue sections but continued to react with CNS myelin in similarly treated sections. The present findings demonstrate the need to consider the role of shielded antigenic determinants in the investigation of antigens or of immune responses.     

Prediction of treatment response in psoriasis with measurement of serum levels of adalimumab,etanercept, and antidrug antibodies: a pilot study

BackgroundA substantial proportion of patients with psoriasis do not respond or lose initial response to tumour necrosis factor antagonists. This may partly be attributable to development of an immunogenic antibody response which causes subtherapeutic drug levels because of the clearance of drug-antidrug complexes. The aim of this study was to investigate the association between serum drug (adalimumab and etanercept) levels, antidrug antibodies, and clinical response in a cohort of psoriasis patients.MethodsIn a single-centre cohort of 56 adults with psoriasis initiated on adalimumab or etanercept between 2009 and 2011, drug and antidrug antibody levels were measured with a commercially available ELISA at the patients’ routine clinic reviews (4, 12, and 24 weeks of treatment and the last available observation). Responders were defined as having a 75% reduction in psoriasis area and severity index from baseline (PASI 75) within 6 months of treatment, or physician's global score of clear or nearly clear. Non-responders were defined as not achieving a 50% reduction in PASI from baseline (PASI 50) within 6 months or having a loss of PASI 50 treatment response.FindingsAfter 4 weeks of therapy, adalimumab levels were significantly higher in responders than in non-responders (median 5·00 μg/mL [IQR 4·30–5·00] vs 0·12 μg/mL [0·10–1·79], p=0·003) and these higher levels were sustained at 12 and 24 weeks. Anti-adalimumab antibodies were detected in 25% of non-responders (2/8 patients, mean follow-up 22·5 weeks) and not in any responders (n=23, mean follow-up 26·1 weeks). There was no significant association between etanercept levels and clinical response at 4 weeks (median 2·94 μg/mL [IQR 0·78–3·68] vs 1·40 [0·82–2·12], p=0·317), and no anti-etanercept antibodies were detected.InterpretationAdalimumab drug level monitoring at 4 weeks may be useful in predicting treatment response, in contrast to etanercept drug levels. The majority of adalimumab non-responders did not have antidrug antibodies; however, lack of serum trough levels and assay limitations may have underestimated their prevalence. Larger studies are required to investigate other factors contributing to low drug levels and to assess the usefulness of these drug and antidrug assays in personalising therapy in psoriasis.FundingNational Institute for Health Research.     

Hematopoietic cell phosphatase associates with erythropoietin (Epo) receptor after Epo-induced receptor tyrosine phosphorylation: identification of potential binding sites

Erythropoietin (Epo) binding to its receptor (EpoR) induces tyrosine phosphorylation in responsive cells and this ability is required for a mitogenic response. One of the substrates of tyrosine phosphorylation is the Epo receptor (EpoR). The carboxyl region of EpoR cytoplasmic domain is required for EpoR phosphorylation and has been shown to negatively affect the response to Epo both in vivo and in cell lines. Hematopoietic cell phosphatase (HCP) has also been hypothesized to negatively regulate erythropoiesis, based on the hypersensitivity to Epo of erythroid lineage cells in moth-eaten mice that genetically lack HCP. In the studies presented here, we show that HCP binds the tyrosine phosphorylated Epo receptor through the amino-terminal src-homology 2 (SH2) domain of HCP. Using a series of phosphotyrosine-containing peptides, potential HCP binding sites in the cytoplasmic domain of the EpoR are identified. The results support the concept that, after Epo stimulation, phosphorylation of EpoR provides a docking site for HCP in the receptor complex. Recruitment of HCP to the complex and its subsequent dephosphorylation of substrates and/or associated kinases may be important to mitigate the ligand-induced mitogenic response.     

The effect of interleukin 3 and GM-CSA-2 on megakaryocyte and myeloid clonal colony formation

Two separate helper T cell-derived lymphokines, interleukin 3 and granulocyte-macrophage colony-stimulating activity-2, were found to stimulate a broad and similar range of hemopoietic colonies in in vitro soft agar cultures including granulocyte, macrophage, granulocyte- macrophage, megakaryocyte, and mixed megakaryocyte colonies. Both lymphokines were potent stimulators of in vitro megakaryocyte colony formation. At plateau levels of IL-3, megakaryocyte colony formation was increased by biologic activity in pokeweed mitogen spleen- conditioned media.     

Hysteroscopic resection of vaginal septum in an adolescent virgin with obstructed hemivagina

This article reports on one patient with a double uterus, unilateral vaginal obstruction, with hemi-haematocolpos and ipsilateral renal agenesis. Early accurate diagnosis followed by the excision of the obstructing vaginal septum offers complete relief of symptoms, while preserving reproductive capacity. Unlike conventional excision of vaginal septum, we used resectoscope excision with cutting electrode under continuous pure distilled water irrigation. The postoperative course was uneventful, and haematocolpos and severe dysmenorrhoea disappeared. The resected vaginal area revealed re-epithelialization by hysteroscope follow-up one year after resection. With advancements in resectoscopic operation, evaluation and treatment of vaginal disorders in babies and virgins is very feasible.      

Cystic teratoma of the ovary: CT detection

Computed tomography (CT) was performed in 38 patients with 41 benign cystic teratomas of the ovary and two patients with malignant transformation. CT depicted all tumors. The presence of fat in 40 of 43 cases (93%), tooth or calcification in 24 of 43 (56%), Rokitansky protuberance in 35 of 43 (81%), tufts of hair in 28 of 43 (65%), and a fat-fluid level in five of 43 (12%) allowed a definite diagnosis of ovarian cystic teratoma in 42 of 43 cases (98%). In the two cases of malignancy, single large (greater than 10 cm) plugs (with uptake of contrast medium in one) with a cauliflower appearance and an irregular border forming an obtuse angle with the inner wall of the cyst suggested malignant transformation. In three cases of benign cystic teratoma, a mucinous tumor (one benign, one borderline, one malignant) arising in the same ovary was seen at pathologic examination but was only diagnosed with the help of CT in two of three cases. Thickening of the tube was noted in two cases of torsion of the adnexa. CT findings were compared with findings at radiography of the abdomen and hysterosalpingography in 30 cases, ultrasound in 31, and magnetic resonance imaging in three. This study demonstrated that CT was the best procedure for imaging cystic teratomas of the ovary.