Aortico-right ventricular tunnel: prenatal diagnosis leading to neonatal survival

In the 36th week of gestation a large aortico-right ventricular tunnel with an otherwise structurally normal heart was diagnosed by fetal echocardiography. This report describes for the first time the impact of the timely prenatal diagnosis of an aortico-right ventricular tunnel followed by successful management in early infancy.     

Neue Ergebnisse zur Frage des Muskel Tonus

Ohne Zusammenfassung     

ACCUMULATION OF ANTIBODIES IN THE CENTRAL NERVOUS SYSTEM

1. Antibodies can be extracted from the brain and spinal cord of rabbits actively or passively immunized with typhoid bacilli. 2. The titers of the antibodies in the extracts of brain and cord depend upon the titer of the blood serum. In actively immunized rabbits the following numerical relationships exist between the titers of the serum and of these organ extracts: The ratio of the titer of the serum is to the titers of extract of brain and of the spinal cord about as 100 is to 0.8; the titer of the serum is to the titer of the cerebrospinal fluid as 100 is to 0.3. In passively immunized rabbits the titer of the serum is to the titer of brain and spinal-cord extract as 100 is to 0.7. 3. The antibodies recovered from the brain are not due to the presence of blood in it for perfusion of the brain does not reduce its antibody content appreciably. 4. Antibodies penetrate into the spinal fluid from the blood even in the absence of inflammation of the meninges. When the penetration is completed the following numerical relationship exists between the titer of the serum and that of the cerebrospinal fluid: 100 to 0.25. 5. The penetration into the cerebrospinal fluid of antibodies injected intravenously proceeds at a slow rate, being completed only several hours after the immune serum has been injected. The penetration of antibodies into the tissue of the brain occurs at a very rapid rate. It is completed within 15 minutes. 6. It is very unlikely that when the immune serum is injected intravenously the antibodies reach the brain tissue by way of the cerebrospinal fluid, for (1) the antibody titer of the cerebrospinal fluid is lower than that of the brain extract, and (2) antibodies penetrate faster into the tissue of the brain than into the cerebrospinal fluid.     

Endotoxin-induced suppression of erythropoiesis: the role of erythropoietin and a heme synthesis stimulating factor

The regulation of erythropoiesis is primarily controlled by erythropoietin (Ep). Recently, however, other factors that both stimulate and inhibit erythropoiesis have been reported. Using an in vitro liquid culture of bone marrow cells, a factor in normal mouse serum was demonstrated that markedly stimulated heme synthesis by marrow erythroid cells. In this study, the role of this heme synthesis stimulating factor (HSF) and Ep in the erythropoietic suppression caused by endotoxin administration to mice was examined. Although HSF levels did not alter appreciably after endotoxin injection, marrow erythroid cells from these animals became unresponsive to the factor. This could be reversed if Ep was added to the culture in vitro or if the hormone was injected into the mice 18 hr prior to harvesting the marrow. This marrow erythroid cell response is identical to that seen in animals in whom Ep levels are markedly reduced, such as that found in exhypoxic polycythemia, and suggest a decrease in the hormone following endotoxin administration. Additional studies demonstrated that when Ep was injected into mice 6 hr after endotoxin administration, an increase in femoral erythroid colony-forming units (CFU-E), proerythroblast number, and 59 Fe incorporation into femoral marrow cells could be demonstrated. These findings, together with the marrow erythroid cell response to the hormone, suggest that the mechanism for suppression of erythropoiesis after endotoxin injection is a reduction in the level of circulating Ep.     

Optical coherence tomographic angiography shows reduced deep capillary flow in paracentral acute middle maculopathy

Introduction

Paracentral acute middle maculopathy (PAMM) has been described as an ischemic lesion of the middle retinal layers with a characteristic lamellar hyper-reflective placoid appearance in the acute phase and thinning of the involved retinal layers in the chronic phase. Optical coherence tomographic angiography (OCTA) is a novel and non-invasive technique for imaging retinal capillary vasculature with en face segmentation capabilities.

Method

Case series. We describe two patients with PAMM who underwent clinical examination and multimodal imaging including OCTA.

Results

In the first patient, who presented with PAMM secondary to acute cilioretinal artery occlusion, OCTA demonstrated reduction in flow in the deep capillary plexus (DCP). One month later, OCTA revealed a flow void due to thinning of the GCL, INL, and OPL and paradoxical apparent ONL thickening. Similar findings of focal retinal lamellar ectopia were seen in the second patient, who had an incidentally detected chronic PAMM lesion.

Conclusions

OCTA images the superficial and deep capillary plexi independently. PAMM is characterized by acute and chronic attenuation of the DCP flow signature. Focal lamellar ectopia in PAMM is discussed.     

The Cdx2 homeobox gene has a tumour suppressor function in the distal colon in addition to a homeotic role during gut development

BACKGROUND: During development, the homeobox gene Cdx2 exerts a homeotic function, providing the positional information necessary for correct specification of the midgut endoderm. This is illustrated by the non-neoplastic gastric-type heteroplasias present at birth in the pericaecal region of Cdx2(+/-) mice. Furthermore, intestinal expression of Cdx2 continues throughout life but diminishes in colorectal cancers compared with adjacent normal tissue, suggesting a role in tumorigenesis. Aim: To investigate the consequence of altered Cdx2 expression on colon tumour initiation and/or progression. METHODS: Heterozygous Cdx2(+/-) mice were analysed for spontaneous malignant tumours and for tumour development after treatment with a DNA mutagen, azoxymethane. RESULTS: Cdx2(+/-) mice did not spontaneously develop malignant tumours. After azoxymethane treatment, the gastric-like heteroplasias in the pericaecal region did not evolve into cancer indicating that they are not precancerous lesions. However, azoxymethane treated Cdx2(+/-) mice developed tumours specifically in the distal colon 12 weeks after azoxymethane treatment whereas no tumours were found in wild-type littermates at this stage. Histopathological and molecular analyses indicated that these tumours were invasive adenocarcinomas that recapitulated the malignant sequence observed in the majority of sporadic colorectal cancers in human. In addition, we found that the colonic epithelium was less sensitive to radiation induced apoptosis in Cdx2(+/-) than in wild-type mice. CONCLUSION: This study provides the first experimental evidence that Cdx2 is a tumour suppressor gene involved in cancer progression in the distal colon. This action in adults is functionally and geographically distinct from its homeotic role during gut development.     

Chemotherapy for mobilisation of Ph-negative progenitor cells from patients with CML: impact of different mobilisation regimens

Mobilised peripheral blood stem cells are widely used for autografting in patients with chronic myeloid leukaemia (CML) and it is generally thought that a high proportion of Ph-negative progenitor cells in the graft is desirable. We report here the results of 91 stem cell mobilisations performed with various chemotherapy regimens followed by G-CSF. We show that mobilisation of Ph-negative cells is possible after diagnosis as well as in advanced stages of the disease. The yield of Ph-negative cells is highly dependent on the chemotherapy regimen: while the combination of idarubicin and cytarabin for 3-5 days (IC3-5) mobilised Ph-negative cells in most patients, high-dose cyclophosphamide was ineffective. Mobilisation of Ph-negative progenitor cells after IC3 was at least as effective as after IC5; however, less apheresis sessions were required, and toxicity was much reduced after IC3. Compared to historical controls, IC was equally effective as the widely used ICE/miniICE (idarubicin, cytarabin, etoposide) protocol. No correlation was found between graft quality and the cytogenetic response to subsequent treatment with interferon-alpha. We conclude that IC3 is an effective and well-tolerated regimen for mobilising Ph-negative cells that compares well with more aggressive approaches such as IC5 and ICE/miniICE.