INTRA-AORTIC BALLOON RUPTURE CAUSING FEMORAL ENTRAPMENT

Rupture of an intra-aortic balloon counterpulsator (IABCP) demands immediate removal. We report a case of thrombus formation within a Datascope IABCP secondary to IABCP rupture, necessitating surgical exploration for removal. There is a disturbing pattern of balloon ruptures with this type of IABCP.     

Ciprofloxacin-induced renal insufficiency in cystic fibrosis.

Acute renal insufficiency is known to occur in patients who are taking ciprofloxacin, particularly the elderly. We report two young patients with cystic fibrosis who presented with acute renal insufficiency after 2-3 weeks of oral ciprofloxacin therapy. The incidence of this adverse effect in children and young adults who have cystic fibrosis is unknown. Multiple mechanisms for ciprofloxacin-induced nephrotoxicity have been proposed.     

Recurrence of posterior uveal melanoma after 60Co episcleral plaque therapy

The authors analyzed the clinical and follow-up data on 277 selected patients with primary choroidal or ciliochoroidal melanoma who were treated with 60Co plaque radiotherapy between 1976 and 1982. Local recurrence of the irradiated melanoma developed in 39 (14%) patients during the follow-up interval. The 5-year tumor recurrence rate (Kaplan-Meier) was estimated to be 12%. Multivariate prognostic factor analysis (Cox proportional hazards modeling) identified the largest linear tumor dimension and proximity of the posterior margin of the tumor to the optic nerve head as predictors of recurrence. The 5-year survival rate of patients whose tumors recurred (58%) was significantly (log-rank test P = 0.0023) worse than that of patients whose tumor remained clinically controlled (82%).     

The association of alcoholism and anxiety

The relationship between alcoholism and anxiety disorders is complex and has been the subject of much investigation. While data from community samples as well as samples of treatment-seeking populations indicate that these disorders co-occur far more commonly than would be expected by chance, the nature of the relationship is unclear. It is clear from both prevalence as well as order of onset data that various anxiety disorders have differing associations with alcohol problems. There is much overlap in symptomatology of panic disorder, generalized anxiety disorder, and alcohol withdrawal. This observation has led to speculation about common neurochemical perturbations and a kindling phenomenon as a possible connection between these disorders. Cognitive theories have been used to connect alcohol abuse and phobic disorders. Treatment of patients with co-morbid anxiety and alcoholism is discussed.     

MR Lymphography with a Lymphotropic T1-Type MR Contrast Agent: Gd-DTPA-PGM

A model system of a paramagnetic lymphotropic MR contrast agent (Gd-DTPA labeled polyglucose associated macrocomplex, PGM) for T¹-weighted MR imaging of lymph nodes in rats and rabbits was evaluated. Pharmacokinetic (tissue accumulation) and MR imaging data (optimal dose and timing parameters) were obtained in normal rats (n = 88) after subcutaneous (SC) injection of paramagnetic, radiolabeled [111In]Gd-DTPA-PGM. A rabbit model of lymph node metastases (n = 8) was ultimately used to demonstrate the potential of MR imaging with Gd-DTPA-PGM for nodal tumor detection. Maximum concentrations of Gd-DTPA-PGM were found in popliteal and paraaortic lymph nodes within 24 h after SC administration, and highest lymph node SNR values were obtained by MR imaging at this time point. The optimum imaging dose was 6–12 μmol Gd/kg. Tumor-lymph node contrast increased from 0.0 ± 1.2 precontrast to 19.2 ± 6.5 (spoiled gradient echo sequence, TR 50/TE 7/flip angle 60°) postcontrast and conspicuity of nodal metastases was improved. Gd-DTPA-PGM accumulates in lymph nodes after SC administration and significantly enhances lymph node signal intensity of normal animals but not metastatic lymph nodes.     

The thyroid axis and desipramine treatment in depression

Although there has been much recent investigation of the role of thyroid function in affective illness, few studies have addressed the effects of the tricyclic antidepressants on the pituitary-thyroid axis. In the present study, thyroid functions (TFTs) and thyrotropin-releasing hormone (TRH) stimulation of thyroid-stimulating hormone (TSH) were measured before and after treatment with desipramine (DMI) in 13 men with a diagnosis of major depressive disorder. All subjects had normal TFTs and baseline TSH measured in a drug-free state at the initiation of the study. Both mean free thyroxine index and baseline TSH decreased after DMI treatment. The amount of decrease in baseline TSH correlated with increase in delta TSH. Four subjects had blunted delta TSH (delta TSH less than or equal to 5 microIU/ml); three of these subjects "normalized" with treatment (delta TSH less than or equal to 5 microIU/ml; greater than or equal to 20 microIU/ml). Two subjects had a high delta TSH, and both "normalized" during treatment. The decrease in both free T4 index and TSH suggests a down-regulation of the thyroid axis at the hypothalamic level. "Normalization" of subtle dysregulation of the thyroid axis is suggested as a mechanism of antidepressant therapy in the treatment of some depressions.     

Redirecting the humoral immune response against Streptococcus mutans antigen P1 with monoclonal antibodies

The adhesin P1 of Streptococcus mutans has been studied as an anticaries vaccine antigen. An anti-P1 monoclonal antibody (MAb) bound to S. mutans prior to mucosal immunization of mice was shown previously to alter the amount, specificity, isotype, and biological activity of anti-P1 antibodies. The present study was undertaken to screen this and four additional anti-P1 MAbs for immunomodulatory activity when complexed with S. mutans and administered by a systemic route and to evaluate sera from immunized mice for the ability to inhibit adherence of S. mutans to immobilized human salivary agglutinin. All five MAbs tested influenced murine anti-P1 serum antibody responses in terms of subclass distribution and/or specificity. The effects varied depending on which MAb was used and its coating concentration. Two MAbs promoted a more effective, and two others a less effective, adherence inhibition response. An inverse relationship was observed between the ability of the MAbs themselves to inhibit adherence and the ability of antibodies elicited following immunization with immune complexes to inhibit adherence. Statistically significant correlations were demonstrated between the levels of anti-P1 serum immunoglobulin G2a (IgG2a) and IgG2b, but not of IgG1 or IgG3, and the ability of sera from immunized animals to inhibit bacterial adherence. These results indicate that multiple anti-P1 MAbs can mediate changes in the immune response and that certain alterations are potentially more biologically relevant than others. Immunomodulation by anti-P1 MAbs represents a useful strategy to improve the beneficial immune response against S. mutans.     

Contribution of the alanine-rich region of Streptococcus mutans P1 to antigenicity, surface expression, and interaction with the proline-rich repeat domain

Streptococcus mutans is considered to be the major etiologic agent of human dental caries. Attachment of S. mutans to the tooth surface is required for the development of caries and is mediated, in part, by the 185-kDa surface protein variously known as antigen I/II, PAc, and P1. Such proteins are expressed by nearly all species of oral streptococci. Characteristics of P1 include an alanine-rich repeat region and a centrally located proline-rich repeat region. The proline-rich region of P1 has been shown to be important for the translational stability and translocation of P1 through the bacterial membrane. We show here that (i) several anti-P1 monoclonal antibodies require the simultaneous presence of the alanine-rich and proline-rich regions for binding, (ii) the proline-rich region of P1 interacts with the alanine-rich region, (iii) like the proline-rich region, the alanine-rich region is required for the stability and translocation of P1, (iv) both the proline-rich and alanine-rich regions are required for secretion of P1 in Escherichia coli, and (v) in E. coli, P1 is secreted in the absence of SecB.     

Identification of a salivary agglutinin-binding domain within cell surface adhesin P1 of Streptococcus mutans.

DNA encoding the alanine-rich region (A-region) of the cell surface adhesin, P1, from Streptococcus mutans was subcloned and expressed as a fusion protein with the maltose-binding protein (MBP) of Escherichia coli. The A-region fusion protein was shown to competitively inhibit both adherence of S. mutans to salivary agglutinin-coated hydroxyapatite and fluid-phase agglutinin-mediated aggregation of this organism. MBP alone or an MBP-paramyosin fusion protein was not inhibitory. Proteolytic cleavage of the fusion protein into its component moieties, MBP and A-region, resulted in breakdown of the A-region into three main fragments. Western immunoblot analysis of calcium-dependent agglutinin binding to this preparation revealed binding specificity for a 28-kDa fragment. Thus, the A-region of P1 is an important domain which interacts directly with salivary agglutinin, and this interaction interferes with both the aggregation and the adherence mechanisms in vitro.     

Identification of non-immunoglobulin A-Fc-binding forms and low-molecular-weight secreted forms of the group B streptococcal beta antigen.

The beta antigen expressed on the surfaces of certain strains of group B streptococci has been reported to bind to the Fc region of human immunoglobulin A (IgA). In this study, we screened 100 isolates of group B streptococci for expression of both beta antigen and IgA-Fc-binding activity. We identified two isolates which expressed the beta antigen but could not bind human IgA Fc fragments and also observed variability in IgA-Fc-binding activity among other beta-antigen-expressing strains. Novel low-molecular-weight forms of beta antigen were secreted by four beta-antigen surface-negative isolates and included IgA-Fc-binding (Mrs, 55,000 and 53,000) and non-IgA-Fc-binding (Mr, 38,000) molecules. These results suggest that the IgA-Fc-binding site represents a unique domain of the beta antigen. The 55,000- and 53,000-Mr forms of secreted beta antigen were functionally and antigenically representative of the size-heterogeneous (Mr, up to 145,000) beta-antigen molecules expressed by surface-positive strains. The cell surface-localized IgA-Fc-binding molecules could bind only human serum IgA efficiently; however, once solubilized, these molecules could bind both human serum and secretory IgAs.