Cost effectiveness evaluation of ADCON-L adhesion control gel in lumbar surgery.

Patients, physicians and third-party payers are becoming increasingly concerned with the economic burden resulting from advances in health care. Many economic health studies have focused on patients with sciatica and low back pain. An Economic Survey was conducted on lumbar discectomy patients who had been enrolled at least 12 months prior in a prospective randomized controlled clinical study of the adhesion control device ADCON-L. The survey measured patient satisfaction, return to work, additional medical treatment and medications after surgery. In addition, the duration of any re-operations from patients in the clinical study was analyzed. The results of the Economic Survey and re-operation time analysis show significant advantages for lumbar discectomy patients who received ADCON-L compared to control patients who did not. Patients who received ADCON-L not only had less scarring and less back pain than control patients but also were more satisfied with their surgeries and were able to return to work more often, as originally planned (p = 0.02). In addition, ADCON-L patients returned to their original jobs an average of 3.6 days sooner, changed jobs 50% less often, did not seek additional medical treatment as often, and took 20% less pain medication than did control patients (p = 0.01). In addition, patients receiving ADCON-L who required subsequent re-operation at the same lumbar space (e.g., reherniation) had a significantly shorter duration of secondary surgery (56.6 min vs. 130 min, p = 0.001) compared to patients who did not receive ADCON-L at the first surgery. Overall, ADCON-L patients demonstrated significant clinical and economic advantages over control patients. If all lumbar surgical patients in the US were to receive ADCON-L, annual savings to the health care system would exceed one half billion dollars.

Effect of atenolol on birth weight.

To investigate the possible harmful effects of early antihypertensive drug therapy with atenolol versus other therapies on pregnancy outcome, we reviewed the records of 398 women referred to our antenatal hypertension clinic between 1980 and 1995. Babies born to women taking atenolol were significantly lighter than babies born to women taking other beta blockers, other antihypertensive drugs, or no therapy, suggesting that atenolol might be detrimental in early pregnancy.

Amyloid beta protein (A beta) removal by neuroglial cells in culture.

Because the mechanisms of A beta degradation in normal and Alzheimer's disease brain are poorly understood, we have examined whether various cortical cells are capable of processing this peptide. Rat microglia and astrocytes, as well as the human THP-1 monocyte cell line, degraded A beta 1-42 added to culture medium. In contrast, neither rat cortical neurons or meningeal fibroblasts effectively catabolized this peptide. When A beta fibrils were immobilized as plaque-like deposits on culture dishes, both microglia and THP-1 cells removed the peptide. Astrocytes were incapable of processing the A beta deposits, but these cells released glycosaminoglycase-sensitive molecules that inhibited the subsequent removal of A beta by microglia. This implied that astrocyte-derived proteoglycans associated with the amyloid peptide and slowed its degradation. The addition of purified proteoglycan to A beta that was in medium or focally deposited also resulted in significant inhibition of peptide removal by microglia. These data suggest that A beta can be catabolized by microglia and proteoglycans which co-localize with senile plaques may slow the degradation of A beta within these pathologic bodies.

Amyloid beta protein levels in cerebrospinal fluid are elevated in early-onset Alzheimer's disease.

The 4-kd amyloid beta protein (A beta) deposited as amyloid in Alzheimer's disease (AD) is produced and released by normal proteolytic processing of the amyloid beta protein precursor (beta APP) and is readily detected in cerebrospinal fluid (CSF). Here, we present the levels of A beta in CSF from a total of 95 subjects, including 38 patients with AD, 14 with early-onset AD and 24 with late-onset AD, 25 normal control subjects, and 32 patients with other neurological diseases. The level of A beta decreased with normal aging, and there was a significant elevation in the level of A beta in the CSF of early-onset AD patients (4.14 +/- 1.37 pmol/ml, p < 0.01). Neither Mini-Mental State nor Functional Assessment Staging were correlated with the amount of A beta in the CSF. The A beta/secreted form of beta APP ratio was elevated, but the level of alpha 1-antichymotrypsin in the CSF did not correlate with the level of CSF A beta in early-onset AD patients. Thus, the level of A beta in the CSF is elevated in early-onset AD patients and is suggested to be correlated with the pathology in the brain that characterizes AD.

Phorbol ester- and glutamate-sensitive phosphorylation of hippocampal membrane proteins from adult and neonatal rats.

The phosphoinositide (PI) second messenger system in the neonatal rat brain is differentially stimulated as compared to that of the adult by agonists such as glutamate. Among the factors that might contribute to the neonatal pattern is the nature of phosphorylated membrane-bound proteins which could regulate this receptor-mediated response. This study was undertaken to compare membrane protein phosphorylation under conditions that affect PI hydrolysis in neonatal and adult rat hippocampus. Two-dimensional gel analysis revealed enhanced basal phosphorylation of two membrane proteins (M(r): 46,000 and 80,000; pI: 4.4 and 4.2, respectively) in the neonatal hippocampus when compared to the adult. The former phosphoprotein is present only in neonatal hippocampus. Phosphorylation of a 48,000 M(r) protein with a pI of 4.5 is prominent in hippocampal membranes from both neonatal and adult rats. After incubation of neonatal hippocampal slices with an active phorbol ester, 12-O-tetradecanoyl phorbol-13-acetate (TPA), all three proteins show decreased post-hoc phosphorylation. Slices from neonatal rats incubated with glutamate demonstrated no alteration in the phosphorylation of any of these proteins, while those from adult rats produced a marked change in phosphorylation of the 80,000 M(r) protein. The data suggest that phosphorylation of this protein from neonates is not yet as efficiently coupled to receptor stimulation as that from the adult. Immunoblot analysis revealed that the 48,000 M(r) protein is the growth-associated protein B-50/GAP-43 and that the 80,000 M(r) protein is a membrane-associated form of the MARCKS protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Production of the Alzheimer amyloid beta protein by normal proteolytic processing.

The 4-kilodalton (39 to 43 amino acids) amyloid beta protein (beta AP), which is deposited as amyloid in the brains of patients with Alzheimer's diseases, is derived from a large protein, the amyloid beta protein precursor (beta APP). Human mononuclear leukemic (K562) cells expressing a beta AP-bearing, carboxyl-terminal beta APP derivative released significant amounts of a soluble 4-kilodalton beta APP derivative essentially identical to the beta AP deposited in Alzheimer's disease. Human neuroblastoma (M17) cells transfected with constructs expressing full-length beta APP and M17 cells expressing only endogenous beta APP also released soluble 4-kilodalton beta AP, and a similar, if not identical, fragment was readily detected in cerebrospinal fluid from individuals with Alzheimer's disease and normal individuals. Thus cells normally produce and release soluble 4-kilodalton beta AP that is essentially identical to the 4-kilodalton beta AP deposited as insoluble amyloid fibrils in Alzheimer's disease.

Effect of serum on lymphocyte blastogenesis. 2. Characterization of disease-induced immunosuppressive factors by chromatography and molecular weight determination.

Numerous infectious and noninfectious diseases are associated with the appearance of suppressive serum lymphocyte immunoregulatory factors (SLIFs). The suppressive SLIFs in sera from clinically healthy dogs and from dogs with bacterial (staphylococcal, brucellar) or mycotic (blastomycotic) infections were further characterized by dialysis, fractionation by ultrafiltrations and HPLC (high performance liquid chromatography) sieving, by affinity chromatography on protein A-Sepharose columns, and by DEAE-cellulose ion exchange chromatography. Factors of various molecular weights and of various elution patterns from DEAE-cellulose and affinity chromatography columns were taking part in the suppressive action of the whole serum. The 'common' inhibitors present in all sera were in the molecular weight range of 28 to 35 Kd, whereas the disease-induced suppressive SLIFs were present in various molecular weight categories. 'Common' suppressor SLIFs and some SLIFs from dogs with staphylococcal infections were partially dialysable; suppressive SLIFs induced in dogs with generalized brucellosis and blastomycosis were not dialysable. Protein A bound suppressive SLIFs from two of three dogs with staphylococcal pyodermas. DEAE-cellulose chromatography gave variable elution patterns with different animal sera. It is concluded that various suppressive SLIFs contribute to the immunosuppressive effect of the whole serum and no disease-specific suppressive SLIF could be identified.

Ascaris suum infection in pigs sensitizes lymphocytes but suppresses their responsiveness to phytomitogens.

The effect of Ascaris suum infection and treatment with fenbendazole on the blastogenic response of peripheral blood lymphocytes to A. suum antigens and to three phytomitogens was assayed by the lymphocyte transformation technique. Repeated infections with A. suum led to the development of sensitized lymphocytes primarily responding to egg hatching fluid antigen. Treatment with fenbendazole decreased the number of specific sensitized lymphocytes, but favorably increased the resistance of pigs to reinfection. Immunity to reinfection did not correlate with the strength of the blastogenic response to A. suum antigens. Repeated infection with A. suum negatively affected the development of the blastogenic response to phytomitogens in the pigs, leading to a partial depression of the responsiveness of lymphocytes and to the partial suppression by serum. Responses to pokeweed mitogen were affected more than the responses to concanavalin A and phytohemagglutinin.

Blastogenesis-suppressing serum factors, decreased immunoglobulin A, and increased beta 1-globulins in Airedale Terriers with diskospondylitis.

In Airedale Terriers with diskospondylitis, immunologic tests revealed heat-stable blastogenesis-suppressing serum factors affecting primarily the effector (phytohemagglutinin-sensitive) lymphocytes; decreased serum concentrations of immunoglobulin A; and increased serum concentrations of undetermined beta 1-globulins. Data indicated that the dogs had decreased immunoglobulin A production and were immunosuppressed, which probably contributed to penetration of bacteria into the body and subsequent spreading to the disks. Eosinophilia and basophilia were also detected, which indicated a potential for a type-I hypersensitivity reaction that may have ameliorated the inflammatory reaction.

Lymphocyte transformation and humoral immune factors in Basenji dogs with immunoproliferative small intestinal disease.

Serum protein concentrations and 4 immunologic factors were determined in 5 Basenji dogs with immunoproliferative small intestinal disease. There was no correlation between the total serum proteins, immunoglobulin G and immunoglobulin M concentrations, and physical health status of the animals. The severity of clinical signs correlated roughly with decrease in albumin and increase in globulin concentrations. The main changes were detected in beta- and fast gamma-globulins. The total hemolytic complement levels were decreased in the 2 most severely affected animals below the minimal laboratory values observed in healthy animals. Alteration in the intrinsic responsiveness of lymphocytes to various mitogens did not correlate with progression in severity of the disease. Correlation between the appearance of blastogenesis-suppressing substances in serum and the severity of the disease was only partial: Sera (at 20% concentration) from the 2 most severely affected dogs completely suppressed blastogenesis induced by all 3 mitogens. The sera of 3 other dogs either did not suppress or suppressed only concanavalin A-induced mitogenesis and to a lesser extent phytohemagglutinin-induced mitogenesis without correlations to the overall clinical status. The disturbances of immunologic mechanisms were detected after the appearance of clinical disease, were not considered the cause of immunoproliferative small intestinal disease, may represent a manifestation of the secondary infection, and may contribute to aggravation of the clinical course.

Effect of serum on lymphocyte blastogenesis. I. Basic characteristics of action by diseased dog serum.

The immunoregulatory effect of serum on phytomitogen-induced lymphocyte blastogenesis was studied in 4 sera from diseased dogs and 1 serum from a clinically healthy dog. The results indicated that: (1) Each of the diseased animals responded to the given infection with a specific pattern of blastogenesis inhibition. (2) The blastogenesis suppression in vitro was proportional to the content of the suppressive serum in the medium. (3) A simultaneous presence of the mitogen and the suppressing "serum's lymphocyte immunoregulatory factors" (SLIF) was necessary for inducing blastogenesis suppression. (4) The suppressive sera most probably acted directly on the cells. (5) The final effect of the sera on lymphocyte blastogenesis was a result of an orchestrated action of blastogenesis-supporting, augmenting, and suppressing SLIF cooperating with the mitogen. (6) The suppressive pattern varied with the individual peripheral blood lymphocytes populations used in the test. (7) The blastogenesis-suppressing SLIF was heat-stable, noncytotoxic, and was not or only partially removable by absorption with peripheral blood lymphocytes. (8) The testing of SLIF activities required the use of various animal lymphocytes and a relatively complex setup of mitogens and control serum combinations for correct interpretations.