A NEW SYNDROME COMBINING PTERYGIUM COLLI WITH DEVELOPMENTAL ANOMALIES OF THE EYELIDS AND LYMPHATICS OF THE LOWER EXTREMITIES.
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The effects of intestinal transplantation on the physiologic functions of the gut are not well understood. Our aim was to determine the effect of a large animal model of small intestinal transplantation (disruption of all neural and lymphatic continuity) on selected absorptive functions of the jejunoileum. Seven dogs were studied before and at 1, 4, and 12 weeks after a model of jejunoileal autotransplantation, which avoids confounding factors of immune rejection, immunosuppression, and harvest ischemia. Jejunal function was assessed by quantitative [3H]-folate and D-xylose absorption and ileal function by quantitative 57Co-vitamin B12 absorption. The role of lymphatic continuity was assessed by fecal fat recovery following 5 days of a controlled, high fat diet (75 g/day). All dogs developed a profuse, watery diarrhea that persisted for 6 to 12 weeks and lost about 15% body weight; however, absorption of D-xylose, folate, and vitamin B12 was unaffected at any time point. Fat absorption postoperatively was only mildly abnormal (less than or equal to 8 g/day) at all time points in five of seven dogs despite complete lymphatic disruption. We concluded that jejunoileal autotransplantation does not markedly affect these specific jejunoileal absorptive functions. Fat absorption in most dogs surprisingly remains almost normal. Anatomic and physiologic consequences of intestinal transplantation do not appear to induce global abnormalities in all absorptive functions in the nonrejecting jejunoileum.
Two patients with Hodgkin's disease in remission and one chronic lymphatic leukemia patient with extraordinarily high anti-Epstein-Barr virus (EBV) (viral capsid antigen) antibody titers (greater than 10,000) were selected to study a spectrum of cell-mediated immune responses, including natural killer, interferon-boosted killer, antibody-dependent lymphocytotoxicity, and T-cell-mediated reactions. The purpose was to compare these reactions in patients with immunosuppression and a high EBV load who can hold their EBV-carrying cells under control with the corresponding reactions in patients with EBV-carrying lymphoproliferative disease. In contrast to the latter group, the three patients of the present study showed a less profound and less general suppression of the immune responses. Multiple effector mechanisms probably safeguard against the proliferation of EBV-transformed B-cells. Clinically manifest EBV-carrying lymphoproliferative disease occurs only in very severe immunodeficiencies effecting multiple effectors.
A lymphatico-osseous communication was demonstrated by lymphangiography in a patient with primary lymphedema of the left leg. The superficial lymph vessels were markedly hyperplastic and contrast medium was visible within the epiphyseal portions of the femur, tibia, fibula, and foot bones. Biopsy of the affected femur showed no abnormality.
Intestinal lymphangiectasia may present as a primary congenital disorder as well as a secondary form due to numerous underlying diseases. Endoscopically, whitish swollen tips of the villi are fairly characteristic; histologically, dilatation of the lymphatics can be demonstrated. By means of electron microscopy dilated intercellular spaces with aggregation of protein precipitations as well as ectatic lymph vessels with abnormal structure are found. Possible relations to the pathomechanism are discussed.
We have isolated a DNA segment absent from all the constitutionally deleted chromosomes 11 of our patients with Wilms tumor. This marker separates two balanced translocations that break in band 11p13: the distal one associated with aniridia (AN2), and the proximal one with genitourinary dysplasia (GUD). The GUD breakpoint maps within the smallest region of overlap (SRO) for the Wilms tumor (WT) gene locus, thus strengthening the previous suggestion of an association between Wilms tumor and other abnormalities of the genitourinary system. The 11p13 translocation breakpoint associated with T-cell acute lymphatic leukemia (T-ALL) is centromeric to the SRO and separated from the WT locus by at least one known gene. This region of the human genome (11p13) is rich in CpG islands that potentially identify genes, some of which may be involved in the various phenotypes associated with the WAGR syndrome. This is consistent with the proposition that the majority of human genes are in G-negative bands.
The cytogenetics of Rauscher murine leukemia virus-induced erythroid, myeloid, and lymphatic leukemias were studied in BALB/c and DBA/2 mice. In primary virus-induced leukemias, no chromosome abnormalities were found. However, in tumors derived from transplanted leukemia tissue and in cell lines obtained from these tumors, euploidy and mostly aneuploidy were observed that varied according to the type of tumor cells and the number of passages. Eleven erythroleukemia cell lines showed aneuploidy from the first in vivo transplant stage on. Nonrandom abnormalities were found: trisomy 15 in 9 of 11 lines, followed by trisomy 3 in 8 of 11 lines and monosomy 6 in 5 of 11 lines. Subsequent evolution of the karyotypes was frequent (10 of 11 lines) and rapid. In vivo cell lines established from these tumors showed many structural rearrangements. Three myeloid lines revealed a stable karyotype with no or only minor changes: trisomy 15 in 1 line and normal diploid in 2 lines. One lymphatic leukemia cell line established in vitro presented with a very stable karyotype: trisomies 14 and 15. Another in vivo transplantable line showed trisomies 11, 9, and 17. These results suggest that trisomy of chromosome 15 plays a significant role in tumors derived from different types of mouse leukemias.
Recent progress in magnetic resonance imaging (MRI) has made it possible to obtain detailed images of the inner ear by delineating the lymphatic fluid within the labyrinth. We analyzed CT scans and MR images in 70 ears manifesting profound deafness owing to inner ear lesions and compared their detective ability for inner ear lesions. The following results were obtained. 1) CT scan examination showed slight to extensive ossification of the labyrinth in six ears (9%), whereas MRI examination revealed low to absent signal intensity of the inner ear in nine ears (13%). Therefore, it was concluded that MRI is more sensitive in detecting abnormalities of the inner ear than CT scan. 2) MRI provided useful information as to whether the cochlear turn is filled with lymphatic fluid or obstructed. This point was one of the greatest advantages of MRI over CT scan. 3) Abnormal findings in either or both the CT scan and the MRI were detected in suppurative labyrinthitis occurring secondary to chronic otitis media, bacterial meningitis and in inner ear trauma. However, such abnormal findings were not detected in patients with idiopathic progressive sensorineural hearing loss, ototoxicity or sudden deafness. These findings should be taken into consideration in pre-operative assessment of cochlear implant candidates.
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Intestinal lymphangiectasia (InL) is a disease characterized by hypoproteinemia and lymphocytopenia resulting from blocked intestinal lymphatics and loss of lymph fluid into the gastrointestinal tract. This leads to immunologic abnormalities including hypogammaglobulinemia, skin anergy and impaired allograft rejection. In the present study, we evaluated whether the above immunologic abnormalities are secondary to a quantitative or qualitative disorder of T cells. In initial studies we demonstrated that adult InL patients' peripheral blood contain strikingly (and significantly) reduced numbers of CD4+/CD45RA+ T cells, whereas the numbers of CD4+/CD45RO+ T cells were only moderately (and not significantly) reduced. In addition, the CD4+/CD45RO+ T cell population contained an increased percentage of highly differentiated and previously sensitized cells, as demonstrated by decreased CD27 and CD31 expression and increased HLA-DR and CD69 expression. In subsequent functional studies, we showed that the InL CD4+/CD45RO+ T cells, when stimulated in vitro, proliferate fivefold less than control CD4+/CD45RO+ T cells and produce fourfold more IL-4 and threefold less IFN-gamma and IL-2. Thus, this cytokine production profile also reflects the highly differentiated nature of the residual cell population. Overall, these studies provide new information on the trafficking of naive/mature and Th1/Th2 T cell populations in this disease model.
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Chronic arm oedema following breast cancer treatment is traditionally attributed to lymphatic obstruction, with venous obstruction as an infrequent complicating factor. The axillo-subclavian venous systems of 81 patients with arm swelling following breast cancer treatment were examined with colour Doppler, duplex Doppler and grey scale ultrasound. Over half (57%) had evidence of venous outflow obstruction and a further 14% had signs of venous "congestion". Only 30% of the swollen arms had normal venous outflow. The venous systems of the contralateral non-swollen arms were all normal as were both arms in 28 control patients who had similar treatment but had not developed arm swelling. These findings suggest that venous outflow obstruction is an important contributory factor in the pathophysiology of arm swelling following breast cancer treatment.
Acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) are thought to arise from malignant hematopoietic progenitor cells representing early and undifferentiated stem cell clones. In CML there is evidence for a progenitor cell subset free of leukemic clones, depending on the course of the disease. Additionally, it has been suggested that in AML, the early stem cell compartment (CD34+/90+) does not harbor the malignant clone. We analyzed white blood cells from leukemia patients for the presence of aberrant cells in stem cell subfractions. Sixteen patients with CML, six patients with AML, two patients with acute lymphatic leukemia (ALL) and one with chronic myelomonocytic leukemia (CMMOL), all with known cytogenetic abnormalities, were evaluated according to their CD90 (Thy-1)-positive or -negative phenotype. Subsets were sorted on to slides and further characterized by FISH and/or standard cytogenetic testing. The bcr-abl translocation or gross chromosomal abnormalities could be detected in equally high amounts of 92.2% and 89.2% in both stem cell subsets. We conclude, that in progressed AML and CML cells characterized by specific genetic aberrations implicated in the malignant state can be found in the CD34+/CD90+ and CD90- population, thus making CD90 an inappropriate marker to distinguish benign from malignant cells in these leukemias.
Anomalies of the inferior vena cava (IVC) have been known since 1793, when Abernethy first described a congenital, mesocaval shunt and azygous continuation of the IVC in a 10-month-old infant with polysplenia and dextrocardia. The IVC is formed by a complex process of embryogenesis during the sixth to tenth week of gestation. It forms from continuous appearance and regression of the three paired veins: posterior cardinal, subcardinal, and supracardinal. Improper completion of the developmental process may result in at least 14 anatomic anomalies, out of which the following four are usually encountered in clinical practice: duplication of the IVC, transposition or left-sided IVC, retroaortic left renal vein, and circumaortic left renal vein. It is suggested that the preoperative diagnosis of the vascular anomalies reduces the complication rate of abdominal vascular procedures. Our vast experience with approximately 400 kidney donors who were evaluated preoperatively with spiral CT scan with three-dimensional reconstruction (3D) reconfirmed this view. Thereafter, it became easier to choose the side and decide between laparoscopic vs. open approach. This prompted us to write the present article focusing on those developmental anomalies of the IVC that may be encountered by the urologist and their implication on the clinical practice.
Vascular endothelial growth factors (VEGFs) are a family of secreted polypeptides with a highly conserved receptor-binding cystine-knot structure similar to that of the platelet-derived growth factors. VEGF-A, the founding member of the family, is highly conserved between animals as evolutionarily distant as fish and mammals. In vertebrates, VEGFs act through a family of cognate receptor kinases in endothelial cells to stimulate blood-vessel formation. VEGF-A has important roles in mammalian vascular development and in diseases involving abnormal growth of blood vessels; other VEGFs are also involved in the development of lymphatic vessels and disease-related angiogenesis. Invertebrate homologs of VEGFs and VEGF receptors have been identified in fly, nematode and jellyfish, where they function in developmental cell migration and neurogenesis. The existence of VEGF-like molecules and their receptors in simple invertebrates without a vascular system indicates that this family of growth factors emerged at a very early stage in the evolution of multicellular organisms to mediate primordial developmental functions.
In an initial pilot study technetium-99m-labelled human serum albumin was perfused directly into bipedal lymphatic cannulae prior to a standard lymphangiogram, in order to assess rapidly normal and abnormal lymph flow patterns in the lower extremity, pelvic and para-aortic lymph chains. A continuing study of these patients has lent further support to the hypothesis that the radionuclide perfusion study, when negative, may prove more accurate in some patients than the standard lymphangiogram in predicting the clinical course and/or the results of histopathological lymph node examination. The radionuclide technique also seems to meet, in this preliminary evaluation, the requirements for a pre-lymphangiogram screening study, particularly for use in high-risk patients.
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