Myectomy versus myotomy as an adjunct to membranectomy in the surgical repair of discrete and tunnel subaortic stenosis

The results of membranectomy and deep myectomy in the left ventricular outflow tract were compared to those of membranectomy and myotomy in 42 patients who underwent surgical repair of discrete and tunnel subaortic stenosis. Fifteen consecutive patients (Group A) underwent membranectomy and myotomy, and 27 consecutive patients (Group B) underwent membranectomy and myectomy. Two patients of Group A and nine of Group B had tunnel subaortic stenosis. The preoperative mean (+/- standard deviation) peak systolic gradients across the left ventricular outflow tract in patients with discrete subaortic stenosis types I and II were 64 +/- 29 mm Hg in Group A and 52 +/- 3 mm Hg in Group B (p = not significant). In the patients with tunnel subaortic stenosis the preoperative mean gradients were 97 +/- 74 mm Hg in Group A and 73 +/- 26 mm Hg in Group B (p = not significant). In patients with discrete subaortic stenosis types I and II, postoperative catheterization at a mean follow-up of 21 months revealed residual mean gradients of 29 +/- 24 mm Hg in Group A and 10 +/- 13 mm Hg in Group B (p less than 0.01). In the patients with tunnel subaortic stenosis, the postoperative mean gradients were 25 +/- 7 and 30 +/- 30 mm Hg in Groups A and B, respectively (p = not significant). We conclude that in the surgical management of discrete subaortic stenosis types I and II, deep myectomy (in addition to membranectomy) produces better relief of the left ventricular outflow obstruction than do membranectomy and myotomy. In patients with tunnel subaortic stenosis myectomy is less effective than in the non-tunnel type but still produces acceptable results and may delay radical procedures to a later age.     

Sequence-specific DNA binding of individual cut repeats of the human CCAAT displacement/cut homeodomain protein.

CCAAT displacement protein (CDP), a nuclear protein of 180-190 kDa, contains a triplicated motif, the cut domain, similar (80-90% conserved) to three repeats of 60-65 amino acids first identified in Drosophila cut, a homeo-domain protein involved in cell-fate decisions in development. Cut repeats bind DNA and exhibit subtle differences in target-site recognition. DNA sequences specifically bound by cut repeats were isolated by PCR-mediated DNA target-site selection. Sequences selected for cut repeat 2 and 3 (CR2 and CR3) binding are A+T-rich and favor an ATA motif with similar, but not identical, flanking base preferences. CR2 and CR3 discriminate among similar target sequences. CR1, which is more divergent from CR2 and CR3, displays the most restricted pattern of DNA sequence recognition. Methylation interference analysis demonstrates different protein-DNA contacts for CR1 and CR3 binding to a target sequence. Thus, CDP/cut is a complex protein whose DNA-binding properties reflect the combinatorial interaction of four domains (three cut repeats and one homeodomain) with target DNA sequences.     

Herpetic croup: two case reports and a review of the literature

Croup is an acute infectious illness usually occurring in children; it is characterized by brassy cough and stridor. The main pathogens include mainly parainfluenza and influenza viruses. Recently there have been reports of prolonged croup caused by the herpes simplex viruses. We report two cases of prolonged croup due to herpes simplex types 1 and 2. We also review and summarize the reported pediatric cases of herpetic croup.     

Short-term enzyme replacement in the murine model of Sanfilippo syndrome type B

The Sanfilippo syndrome type B (MPS III B) is an autosomal recessive disease caused by deficiency of alpha-N-acetylglucosaminidase (EC 3. 2.1.50), one of the lysosomal enzymes required for the degradation of heparan sulfate. The disease is characterized by profound neurodegeneration but relatively mild somatic manifestations, and is usually fatal in the second decade. A mouse model had been generated by disruption of the Naglu gene in order to facilitate the study of pathogenesis and the development of therapy for this currently untreatable disease. Recombinant human alpha-N-acetylglucosaminidase (rhNAGLU) was prepared from secretions of Lec1 mutant Chinese hamster ovary cells. The enzyme, which has only unphosphorylated high-mannose carbohydrate chains, was endocytosed by mouse peritoneal macrophages via mannose receptors, with half-maximal uptake at ca. 10(-7) M. When administered intravenously to 3 month-old mice, rhNAGLU was taken up avidly by liver and spleen but marginally if at all by thymus, lung, kidney, heart, and brain (in order of diminishing uptake). The half-life of the enzyme was 2.5 days in liver and spleen. Immunohistochemistry and electron microscopy showed that only macrophages were involved in enzyme uptake and correction in these two organs, yet the storage of glycosaminoglycan was reduced to almost normal levels. The results show that the macrophage-targeted rhNAGLU can substantially reduce the body burden of glycosaminoglycan storage in the mouse model of Sanfilippo syndrome III B.     

Deletion of 20p 11.23→pter with normal growth hormone-releasing hormone genes

Using a molecular analysis of the DNA from a patient with a deletion of chromosome 20 [46,XX,del(20)(p11.23)], we have excluded the growth hormone-releasing hormone (GHRH) gene from the region 20p11.23→pter. The patient had minor facial anomalies, Rieger eye anomaly, a congenital heart defect, severe failure to thrive, and a neurosecretory problem in growth hormone (GH) secretion. Since the GHRH gene was previously mapped to chromosome 20, we used molecular genetic methods to determine whether the growth abnormalities were due to the deletion of this gene. DNAs of the patient and 2 normal control subjects were analyzed by quantitative Southern blotting using a DNA probe for the GHRH gene and 2 reference DNA probes mapping to chromosome 21. The GHRH gene was found to be present in 2 copies in the patient. This indicates that the gene for GHRH maps to the region outside the patient's deletion, in 20p11.23→qter. Furthermore, our results suggest that genes other than GHRH on 20p are important for developmental steps leading to normal neurosecretory function of GH and may also be involved in generating Rieger eye anomaly. Finally, GH deficiency and Rieger eye anomaly should be sought in other patients with deletions of 20p.     

Primitive Neuroectodermal Tumors of the Central Nervous System

Controversial issues relating to the pathobiology and classification of central nervous system primitive neuroectodermal tumors (PNETs) have plagued neuropathologists for more than 70 years. Hypotheses advanced in the mid-1920's have remained as fixed concepts in contemporary literature, largely consequent to repetitious support by a small number of neuropathologists despite a growing body of information discrediting these ideas from neuroembryologists, oncologists, neuroscien-tists and pathologists.
Attention has largely focused upon PNETs arising in the cerebellum (commonly known as medul-loblastomas [MBs]), because about 80% of central nervous system (CNS) PNETs originate in this site. It has been asserted that the 20% which do not are biologically different, although most individuals agree that the histological features of PNETs that occur in different sites throughout the CNS are indistinguishable from those growing in the cerebellum.
The historical aspects of this controversy are examined in the face of evidence that there is, in fact, a unique class of CNS tumors which should appropriately be regarded as primitive neuroectodermal in nature. Specifically, a number of different approaches to the problem have yielded data supporting this hypothesis. These approaches include the identification of patterns of expression among a variety of cellular antigens (demonstrated by the use of immunopathological techniques), molecular analyses of cell lines derived from these tumors, experimental production of PNETs and molecular genetic analyses.
Differences of opinion among surgeons, oncologists and radiotherapists are typically resolved by conducting cooperative studies of patients with these tumors who are diagnosed and treated at multiple centers.     

Stereotypic responses to infection and inflammation

There is a sequence of Stereotypie metabolic changes in rats subjected to inflammation or infection. In each stress, rats respond with increases in body temperature and plasma insulin and with decreases in plasma zinc, ketone bodies, and free fatty acids. The data suggest that infection or inflammation causes an activation of phagocytic cells and also that leukocytic endogenous mediator, when injected into rats, causes some of the same alterations. Rats doubly vagotomized respond to infection in the same fashion as intact rats.In conducting the research described in this report, the investigators adhered to the Guide for the Care and Use of Laboratory Animals, as promulgated by the Committee on Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources, National Research Council. The facilities are fully accredited by the American Association for Accreditation of Laboratory Animal Care.The views of the authors do not purport to reflect the positions of the Department of the Army or the Department of Defense.     

Versuche einer passiven Übertragung der Tuberkuloseimmunität an Schafen

Ohne Zusammenfassung     

Deletion of 20p 11.23----pter with normal growth hormone-releasing hormone genes

Using a molecular analysis of the DNA from a patient with a deletion of chromosome 20 [46,XX,del(20)(p 11.23)], we have excluded the growth hormone-releasing hormone (GHRH) gene from the region 20p11.23----pter. The patient had minor facial anomalies. Rieger eye anomaly, a congenital heart defect, severe failure to thrive, and a neurosecretory problem in growth hormone (GH) secretion. Since the GHRH gene was previously mapped to chromosome 20, we used molecular genetic methods to determine whether the growth abnormalities were due to the deletion of this gene. DNAs of the patient and 2 normal control subjects were analyzed by quantitative Southern blotting using a DNA probe for the GHRH gene and 2 reference DNA probes mapping to chromosome 21. The GHRH gene was found to be present in 2 copies in the patient. This indicates that the gene for GHRH maps to the region outside the patient's deletion, in 20p11.23----qter. Furthermore, our results suggest that genes other than GHRH on 20p are important for developmental steps leading to normal neurosecretory function of GH and may also be involved in generating Rieger eye anomaly. Finally, GH deficiency and Rieger eye anomaly should be sought in other patients with deletions of 20p.     

Does complete revascularization by the conventional method truly provide the best possible results? Analysis of results and comparison with revascularization of infarct-prone segments (systematic segmental myocardial revascularization): the Sheba Study

Myocardial revascularization is usually considered "complete" if all stenosed major coronaries are bypassed. Attempts were made to compare the results of this method with an approach by which each of the following five left ventricular infarct-prone segments is revascularized if ischemic: anteroseptal, anterolateral, posterosuperior, posteroinferior, and diaphragmatic. Two subsets of patients were studied. A total of 366 patients (Group A) who underwent aortacoronary bypass operations from 1980 to 1982 were followed up for a mean of 16.3 (6 to 43) months and were retrospectively divided into two groups: Group A1 (120 patients) had incomplete segmental revascularization (mean of 3.4 grafts per patient) and Group A2 (246 patients) had complete segmental revascularization (4.0 grafts per patient) (p less than 0.0001). Groups A1 and A2 were identical in all clinical and angiographic parameters: unstable angina, 60%; previous myocardial infarction, 70%; left main stenosis, 10%; and ejection fraction less than 30%, 2%. Overall operative mortality was 2.3%. Results in Groups A1 and A2, respectively, were as follows: operative mortality, 5.8% versus 0.8% (p less than 0.005); perioperative myocardial infarction, 6.9% versus 0.8% (p less than 0.0005); 35 month survival rate, 93.3% versus 97.9% (p less than 0.02); total freedom from symptoms, 54.1% versus 68.3% (p less than 0.025). In addition, 151 patients operated on in 1984 (Group B) were studied prospectively with regard to operative mortality and perioperative myocardial infarction, and the results were identical to those in Group A. Compared to conventional complete revascularization, complete segmental revascularization provides better results.