The heparin-induced thrombocytopenia and thrombosis syndrome: Treatment with intraarterial urokinase and systemic platelet aggregation inhibitors

We report a case of the heparin-induced thrombocy-topenia and thrombosis syndrome presenting with acute ischemia of a lower limb. The patient was successfully treated by withdrawal of heparin products, intraarterial urokinase, and platelet anti-aggregation therapy consisting of Dextran and aspirin.     

What Motivates Participation and Dropout Among Low‐Income Urban Families of Color in a Prevention Intervention?*

Low‐income urban parents of color enrolled in a parent training study were interviewed to understand what motivated their participation and what led 30% of them to subsequently drop out. Most enrolled because they wanted to be better parents. Most dropped out because of time and schedule constraints. Retention was higher when parents' motivations for participation matched program goals. Program location and qualities of the recruiter were cited most often as important; financial compensation was cited least often as important.     

Functional interactions between putative intramembrane charged residues in the lactose permease of Escherichia coli.

Using a lactose permease mutant devoid of Cys residue ("C-less permease"), we systematically replaced putative intramembrane charged residues with Cys. Individual replacements for Asp-237, Asp-240, Glu-269, Arg-302, Lys-319, His-322, Glu-325, or Lys-358 abolish active lactose transport. When Asp-237 and Lys-358 are simultaneously replaced with Cys and/or Ala, however, high activity is observed. Therefore, when either Asp-237 or Lys-358 is replaced with a neutral residue, leaving an unpaired charge, the permease is inactivated, but neutral replacement of both residues yields active permease [King, S. C., Hansen, C. L. & Wilson, T. H. (1991) Biochim. Biophys. Acta 1062, 177-186]. Remarkably, moreover, when Asp-237 is interchanged with Lys-358, high activity is observed. The observations provide a strong indication that Asp-237 and Lys-358 interact to form a salt bridge. In addition, the data demonstrate that neither residue nor the salt bridge plays an important role in the transport mechanism. Thirteen additional double mutants were constructed in which a negative and a positively charged residue were replaced with Cys. Only Asp-240-->Cys/Lys-319-->Cys exhibits significant activity, accumulating lactose to 25-30% of the steady state observed with C-less permease. Replacing either Asp-240 or Lys-319 individually with Ala also inactivates the permease, but double mutants with neutral substitutions (Cys and/or Ala) at both positions exhibit essentially the same activity as Asp-240-->Cys/Lys-319-->Cys. In marked contrast to Asp-237 and Lys-358, interchanging Asp-240 and Lys-319 abolishes active lactose transport. The results demonstrate that Asp-240 and Lys-319, like Asp-237 and Lys-358, interact functionally and may form a salt bridge. However, the interaction between Asp-240 and Lys-319 is clearly more complex than the interaction between Asp-237 and Lys-358. In any event, the findings suggest that putative transmembrane helix VII lies next to helices X and XI in the tertiary structure of lactose permease.     

Technique and early clinical results of endoscopic variceal ligation (EVL)

Summary Endoscopic variceal ligation (EVL) is a new technique designed to be used instead of sclerotherapy. Small elastic O rings ligate varices resulting in their strangulation and eradication. During a 12-month period, EVL was employed in 53 consecutive patients, of whom 36 (68%) had alcoholic cirrhosis 17 were Child-Pugh class A, 22 class B, and 14 class C. Varices were graded from I to IV and repeat treatments were given at 1–2 week intervals until the varices were eliminated. At follow-up ranging from 6–18 months (mean 11.5), 217 EVL treatment sessions had been performed. Of the 13 patients (24%) who died during the study, 11 died during the index hospitalization. Active bleeding was controlled in 19 of 21 patients (90%). Of 40 survivors 13 patients (33%) had 1–2 (mean 1.4) recurrent variceal bleeds while 34 patients had repeat EVL treatment. Elimination of distal varices was achieved in 26 and 7 had reduction of varices from grade III–IV to grade I–II or less. Eradication required a mean of 4.4 EVL sessions in Child's A and B patients and 7.0 sessions in Child's C patients (P<0.025). No significant treatment-related complications were observed. EVL appears to control active bleeding, is associated with a low incidence of non-bleeding complications, and may be used as an alternative to sclerotherapy.     

The effects of short-term smokeless tobacco deprivation on performance

Several past studies have reported reliable changes in reaction time performance and self-rated withdrawal scores as a consequence of cigarette deprivation. The purpose of the present study was to determine, prospectively, the effect 24 h of smokeless tobacco deprivation in regular users has on performance and the associated withdrawal symptomology. Forty smokeless tobacco users (Copenhagen brand) were randomly divided evenly into two groups gen brand) were randomly divided evenly into two groups (N=20)24 h of deprivation and no deprivation. A third group of ten nonchewers was added as another control group. The results indicated that behavioral, subjective and physiological changes are associated with smokeless tobacco deprivation in regular users. These include increased craving scores, reaction time, self-rated withdrawal symptoms and decreased heart rate.     

Hemolytic uremic syndrome after bone marrow transplantation: clinical characteristics and outcome in children.

Hemolytic uremic syndrome (HUS) is an uncommon but potentially life-threatening complication of hematopoietic stem cell transplantation. We retrospectively studied the medical records of 293 children who underwent allogeneic bone marrow transplantation at St. Jude Children's Research Hospital between 1992 and 1999 to describe the clinical course of and to identify risk factors for transplant-associated HUS. Conditioning regimens included cyclophosphamide, cytarabine, and total body irradiation for patients with hematologic malignancies (n = 244); patients with nonmalignant diseases (n = 49) received disease-specific regimens. Grafts from unrelated or mismatched related donors were depleted of T lymphocytes, whereas matched sibling grafts were unmanipulated. All patients received cyclosporine as prophylaxis for graft-versus-host disease. Recipients of grafts from matched siblings also received pentoxifylline or short-course methotrexate. HUS developed in 28 (9.6%) patients at a median of 171 days after transplantation. We identified older donor age (P = .029), use of antithymocyte globulin in the conditioning regimen (P = .008), and recipient CMV seronegativity (P = .011) as being associated with an increased risk of HUS. With a multiple regression analysis, the use of antithymocyte globulin (beta = .86; P = .04) and recipient cytomegalovirus seronegativity (beta = .93; P = .035) remained significant risk factors for the development of HUS.     

A natural musaceas plant extract inhibits proteasome activity and induces apoptosis selectively in human tumor and transformed, but not normal and non-transformed, cells

Animal studies have demonstrated that a dietary polyphenol known as tannic acid (TA) exhibits anticarcinogenic activity in chemically induced cancers. Most recently, we have reported that TA and ester-bond containing green tea polyphenols are potent proteasome inhibitors in vitro and in vivo. We hypothesize that CellQuest, a patented formula which contains high level of TA obtained from a musaceas (plantain) plant extract, will inhibit the tumor cell proteasome activity. Here, we report that a partially purified CellQuest fraction, S3, potently inhibits the proteasomal chymotrypsin-like activity of Jurkat T cell extracts in a concentration-dependent manner. Inhibition of the proteasome by S3 in leukemia Jurkat T, simian virus 40-transformed and prostate cancer LNCaP cells results in accumulation of ubiquitinated proteins and the natural proteasome substrate p27Kip1, followed by induction of apoptosis. In contrast, non-transformed, immortalized human natural killer cells and normal human fibroblasts are resistant to S3-mediated proteasome inhibition and apoptosis induction. Our present study suggests that CellQuest targets and inhibits the proteasome selectively in tumor cells, which may contribute to the claimed anticancer activity.     

Mitochondrial Antibodies in Primary Biliary Cirrhosis: II. The Complement Fixing Antigen as a Component of Mitochondrial Inner Membranes

The autoantibodies found in the sera of patients with primary biliary cirrhosis have been shown to react with a component of the mitochondrial inner membranes. Outer membranes were inactive. The purity of the inner and outer membrane fractions obtained by 2 different methods was assessed by electron microscopy and marker enzyme tests. Using negative-staining it was possible to visualize antibody binding to mitochondrial membranes. At high resolution it could be seen that the 90° particles on the cristal membranes were not involved in the reaction with antibody, but it was not possible to establish in the present studies the precise antigenic site upon the mitochondrial inner membranes.     

Coronary heart disease, chronic inflammation, and pathogenic social hierarchy: a biological limit to possible reductions in morbidity and mortality

We suggest that a particular form of social hierarchy, which we characterize as "pathogenic", can, from the earliest stages of life, exert a formal analog to evolutionary selection pressure, literally writing a permanent developmental image of itself upon immune function as chronic vascular inflammation and its consequences. The staged nature of resulting disease emerges "naturally" as a rough analog to punctuated equilibrium in evolutionary theory, although selection pressure is a passive filter rather than an active agent, like structured psychosocial stress. Exposure differs according to the social constructs of race, class, and ethnicity, accounting in large measure for observed population-level differences in rates of coronary heart disease across industrialized societies. American Apartheid, which enmeshes both majority and minority communities in a social construct of pathogenic hierarchy, appears to present a severe biological limit to continuing declines in coronary heart disease for powerful as well as subordinate subgroups: "Culture"--to use the words of the evolutionary anthropologist Robert Boyd--"is as much a part of human biology as the enamel on our teeth".