Biodegradable gelatin/beta-tricalcium phosphate sponges incorporating recombinant human fibroblast growth factor-2 for treatment of recession-type defects: A split-mouth study in dogs.

BACKGROUND AND OBJECTIVE: Tissue engineering by using recombinant human (rh) growth factor technology may offer a promising therapeutic approach for treatment of gingival recession. Fibroblast growth factor-2 (FGF-2) has shown the ability to promote periodontal regeneration. Gelatin/beta-tricalcium phosphate (gelatin/ß-TCP) sponges have been developed to control the release of growth factors. The present study evaluated the periodontal regenerative efficacy of rhFGF-2 by comparing gelatin/ß-TCP sponges incorporated with rhFGF-2 to the scaffolds alone in artificially created recession-type defects in dogs. MATERIAL AND METHODS: Critically sized buccal gingival recession defects were surgically created on maxillary canine teeth of five dogs. In each animal, defects were randomized to receive either a gelatin/ß-TCP sponge soaked with rhFGF-2 (gelatin/ß-TCP/rhFGF-2) or phosphate-buffered saline (gelatin/ß-TCP). Eight weeks after surgery, biopsy specimens were obtained and subjected to microcomputed tomography and histological analyses. RESULTS: Complete root coverage was achieved in both groups. Microcomputed tomography revealed significantly greater new bone volume in the gelatin/ß-TCP/rhFGF-2 group. Histologically, both groups achieved periodontal regeneration; however, gelatin/ß-TCP/rhFGF-2 sites exhibited more tissue regeneration, characterized by significantly larger amounts of new cementum and new bone. Gelatin/ß-TCP sites featured increased long junctional epithelium and connective tissue attachment. In the gelatin/ß-TCP/rhFGF-2 sites, new bone exhibited many haversian canals and circumferential lamellae as well as remarkably thick periosteum with blood vascularization and hypercellularity. CONCLUSION: Within the limitations of this study, rhFGF-2 in gelatin/ß-TCP sponges exhibits an increased potential to support periodontal wound healing/regeneration in canine recession-type defects.

Ridge augmentation using recombinant human fibroblast growth factor-2 with biodegradable gelatin sponges incorporating ß-tricalcium phosphate: a preclinical study in dogs.

BACKGROUND AND OBJECTIVE: Fibroblast growth factor-2 (FGF-2) regulates the proliferation and differentiation of osteogenic cells, resulting in the promotion of bone formation. Biodegradable gelatin sponges incorporating ß-tricalcium phosphate (ß-TCP) have been reported as a scaffold, which has the ability to control growth factor release, offering sufficient mechanical strength and efficient migration of mesenchymal cells. In this study, we evaluated the effects of the combined use of recombinant human FGF-2 (rhFGF-2) and gelatin/ß-TCP sponge on ridge augmentation in dogs. MATERIAL AND METHODS: Six male beagle dogs were used in this study. Twelve wk after tooth extraction, bilateral 10 × 5 mm (width × depth) saddle-type defects were created 3 mm apart from the mesial side of the maxillary canine. At the experimental sites, the defects were filled with gelatin/ß-TCP sponge infiltrated with 0.3% rhFGF-2, whereas gelatin/ß-TCP sponge infiltrated with saline was applied to the control sites. Eight wk after surgery, qualitative and quantitative analyses were performed. RESULTS: There were no signs of clinical inflammation at 8 wk after surgery. Histometric measurements revealed that new bone height at the experimental sites (2.98 ± 0.65 mm) was significantly greater than that at the control sites (1.56 ± 0.66 mm; p = 0.004). The total tissue height was greater at the experimental sites (6.62 ± 0.66 mm) than that at the control sites (5.95 ± 0.74 mm), although there was no statistical significant difference (p = 0.051). Cast model measurements revealed that the residual defect height at the experimental sites (2.31 ± 0.50 mm) was significantly smaller than that at the control sites (3.51 ± 0.78 mm; p = 0.012). CONCLUSION: The combined use of rhFGF-2 and gelatin/ß-TCP sponge promotes ridge augmentation in canine saddle-type bone defects.

Effect of a tunnel-structured ß-tricalcium phosphate graft material on periodontal regeneration: a pilot study in a canine one-wall intrabony defect model.

BACKGROUND AND OBJECTIVE: Tissue regeneration is affected by the porosity, chemical properties and geometric structure of graft materials. Regeneration of severe periodontal defects, such as one-wall intrabony defects, is difficult because of reduced tissue support, and bone grafts are commonly used in such cases. In the present study, a tunnel-structured ß-tricalcium phosphate (tunnel ß-TCP) graft material designed to stimulate bone formation was fabricated. The objective of this pilot study was to evaluate the effect of this graft material on periodontal regeneration in one-wall intrabony defects in dogs. MATERIAL AND METHODS: Six male beagle dogs were used in this study. First, the mandibular second and third incisors were extracted. Experimental surgery was performed 12 wk after tooth extraction. Bilateral 4 × 8 mm (width × depth) one-wall intrabony defects were created in the mesial side of the mandibular canines. At the experimental sites, the defects were filled with tunnel ß-TCP, whereas the control defects were left empty. Twelve weeks after surgery, qualitative and quantitative histological analyses were performed. RESULTS: There were no signs of clinical inflammation 12 wk after surgery. Coronal extension indicative of new bone formation was higher at the experimental sites than at the control sites, although the differences between both the sites in the newly formed cementum and connective tissue attachment were not significant. Newly formed periodontal ligament and cementum-like tissue were evident along the root surface at the experimental sites. The inner surface of the tunnels was partially resorbed and replaced with new bone. New blood vessels were observed inside the lumens of tunnel ß-TCP. CONCLUSION: Tunnel ß-TCP serves as a scaffold for new bone formation in one-wall intrabony defects.

Economic evaluation of chemoprevention of breast cancer with tamoxifen and raloxifene among high-risk women in Japan.

Raloxifene was approved for chemoprevention against breast cancer among high-risk women in addition to tamoxifen by the US Food and Drug Administration. This study aims to evaluate cost-effectiveness of these agents under Japan's health system. A cost-effectiveness analysis with Markov model consisting of eight health states such as healthy, invasive breast cancer, and endometrial cancer is carried out. The model incorporated the findings of National Surgical Adjuvant Breast and Bowel Project P-1 and P-2 trial, and key costs obtained from health insurance claim reviews. Favourable results, that is cost saving or cost-effective, are found by both tamoxifen and raloxifene for the introduction of chemoprevention among extremely high-risk women such as having a history of atypical hyperplasia, a history of lobular carcinoma in situ or a 5-year predicted breast cancer risk of > or =5.01% starting at younger age, whereas unfavourable results, that is 'cost more and gain less' or cost-ineffective, are found for women with a 5-year predicted breast cancer risk of < or =5.00%. Therapeutic policy switch from tamoxifen to raloxifene among postmenopausal women are implied cost-effective. Findings suggest that introduction of chemoprevention targeting extremely high-risk women in Japan can be justifiable as an efficient use of finite health-care resources, possibly contributing to cost containment.

Docetaxel plus prednisolone for the treatment of metastatic hormone-refractory prostate cancer: a multicenter Phase II trial in Japan.

BACKGROUND: Docetaxel-based chemotherapy has been shown to be effective and well tolerated by Western patients with metastatic hormone-refractory prostate cancer (HRPC). This study was undertaken to assess the feasibility of docetaxel in combination with prednisolone in Japanese patients with HRPC. METHODS: Patients aged 50-74 years with measurable metastatic HRPC were included in this non-comparative Phase II study. Treatment consisted of docetaxel 70 mg/m(2) once every 3 weeks plus prednisolone 5 mg twice daily, for a maximum of 10 cycles. The primary endpoint was overall tumor response rate, assessed by Response Evaluation Criteria in Solid Tumors; secondary endpoints included prostate-specific antigen (PSA) response and toxicity. RESULTS: A total of 43 patients were evaluable for efficacy and toxicity. The response rate was 44.2% (90% CI, 31.2-57.8%), with partial responses in 19/43 patients. The median duration of response was 19.3 weeks. PSA responses were recorded in 44.4% of patients (95% CI, 27.9-61.9%). The most common non-hematological adverse events (of any grade) possibly related to treatment were alopecia (88.4%), anorexia (65.1%) and fatigue (53.5%). Grade 3/4 leukopenia and neutropenia occurred in 81.4 and 93.0% of patients, respectively; however, the grade 3/4 rates of febrile neutropenia (16.3%) and infection without fever (14.0%) were lower. CONCLUSION: The combination of docetaxel and prednisolone was feasible and active in Japanese patients with HRPC, with a manageable adverse-event profile similar to that observed in Western patients.

Reassessment of the clinical significance of portal-superior mesenteric vein invasion in borderline resectable pancreatic cancer.

OBJECTIVE: The principal objective of this study is to clarify the prognostic significance of borderline resectable pancreatic cancer (BRPC). The second objective is to evaluate the prognostic impact of the depth of pathological venous invasion. METHODS: The study included 122 pancreatic cancer patients who underwent curative surgery. All computed tomography scans of the patients were retrospectively interpreted and classified according to the NCCN guidelines, version 1.2016, as resectable (-) or borderline resectable (+) in each arterial (BR-A) and venous (BR-PV) involvement. RESULTS: The overall survival (OS) rate was significantly higher in BR-A(-) patients (n = 94) than in BR-A(+) patients (n = 28) (P = 0.001), whereas there was no difference between BR-PV(-) (n = 101) and BR-PV(+) patients (n = 21) (P = 0.257). In a multivariate analysis, the independent predictors of OS included BR-A(+) (P = 0.002), lymph node metastasis (P = 0.008), pathological venous invasion (P = 0.003), and adjuvant chemotherapy (P = 0.001). Of 39 patients who underwent venous resection, no significant difference was observed between BR-PV(-) (n = 20) and BR-PV(+) patients (n = 19) in resection rate, lymph node metastasis, the presence of extrapancreatic nerve invasion, recurrence rate, frequency of initial recurrence at a liver or local site, and OS. Pathological venous invasion was significantly deeper in BR-PV(+) patients. However, the depth of invasion was not associated with OS. CONCLUSION: The definition of venous involvement in the current guidelines predicted the depth of pathological venous invasion but not OS in BRPC patients. Further prospective, randomized studies are needed to establish treatment strategies for BRPC patients with isolated venous involvement.

Risk factors for aerobic bacterial conjunctival flora in preoperative cataract patients.

PurposeTo investigate the relationship between the background of preoperative cataract patients and bacterial conjunctival flora.MethodsA total of 990 cataract patients who had completed preoperative examinations in 2007 and 2008 were included. Patients using topical antibiotics at the preoperative examination or having a history of intraocular surgery were excluded. Conjunctival cultures had been preoperatively obtained. Patient characteristics were investigated via medical records. Risk factors for conjunctival flora of seven typical bacteria were analyzed by univariate and multivariate analyses.ResultsThe detection rate of alpha-hemolytic streptococci and Enterococcus faecalis increased with age (P=0.044 and P=0.002, respectively). The detection rate of Gram-negative bacilli was higher among patients with oral steroid use or lacrimal duct obstruction (P=0.038 and P=0.002, respectively). The detection rate of Corynebacterium species was higher among older patients and men, and lower among patients with glaucoma eye drop use (P<0.001, P=0.012 and P=0.001, respectively). The detection rate of methicillin-susceptible coagulase-negative Staphylococci was higher among men and lower among patients with a surgical history in other departments (P=0.003 and P=0.046, respectively). The detection rate of methicillin-resistant coagulase-negative Staphylococci (MR-CNS) was higher among patients with oral steroid use, a visit history to ophthalmic facilities, or a surgical history in other departments (P=0.002, P=0.037 and P<0.001, respectively).ConclusionsElderly patients, men, patients with lacrimal duct obstruction or immunosuppressed patients are more likely to be colonized by pathogens that cause postoperative endophthalmitis. Moreover, MR-CNS colonization was associated with healthcare-associated infection.

Immunological detection of glycated proteins in normal and streptozotocin-induced diabetic rats using anti hexitol-lysine IgG.

A polyclonal antibody specific for the Amadori compound, a product of an early stage of the Maillard reaction, was raised in rabbits by immunization with hexitol-lysine (1-glucitol-lysine or 1-mannitol-lysine) coupled with various carrier proteins. The affinity purified antibody has a high titre and preferentially recognizes the glucose adduct, in the presence of sodium borohydride, as judged on enzyme-linked immunosorbent assay as well as immunoblot analysis. The glycated proteins (Amadori products) in various tissues of normal and streptozotocin-induced diabetic rats were examined by immunoblot analysis. In diabetic conditions, kidney, liver, lens, brain and lung proteins are more susceptible to glycation than other tissue proteins. Heart, spleen, adrenal gland and muscle proteins exhibit similar extents of glycation in both normal and diabetic conditions. This is the first demonstration of a specific antibody against the Amadori compound being raised with a synthetic compound, and of the tissue distribution of glycated proteins in normal and diabetic conditions. The antibody was very useful for in vitro and in vivo experiments on the Maillard reaction.

Preparation of human manganese superoxide dismutase by tri-phase partitioning and preliminary crystallographic data.

Human liver manganese superoxide dismutase has been purified by a short procedure that includes a tri-phase partitioning step to provide materials that can be crystallized from ammonium sulfate. X-ray diffraction studies at 3 A resolution show that the crystals belong to the hexagonal space group P6(1)22 or P6(5)22, with cell dimensions a = b = 81.1 A, c = 242.2 A. Manganese superoxide dismutase levels as determined by enzymatic assay as well as by enzyme-linked immunosorbent assay indicated that considerable variations occur in different livers but the total superoxide dismutase activity (Mn superoxide dismutase plus Cu,Zn superoxide dismutase) seems to be kept at constant values.

Analysis of the immunoglobulin heavy chain gene variable region of CD5-positive and -negative diffuse large B cell lymphoma.

We analyzed nucleotide sequence and intraclonal diversity of the rearranged immunoglobulin heavy chain gene variable region (VH gene) of CD5+ and CD5- diffuse large B cell lymphoma (DLBCL) to clarify the cell origin of de novo CD5+ DLBCL. Ten cases of CD5+ DLBCL and 29 cases of CD5- DLBCL were analyzed. The frequencies of somatic mutation were 0.7 to 12.9% (average, 6.2%) in CD5+ DLBCL and 2.0 to 25.9% (average, 11.1%) in CD5- DLBCL. The ongoing mutation rate was estimated from the number of further single base-substitutions, expressed as a percentage of the total number of nucleotides in 10 cloned PCR products for each case (%). The averages of the ongoing mutation rate of CD5+ DLBCL (four cases) and CD5 DLBCL (seven cases) were 0.051% and 0.197%, respectively. The rate of CD5+ DLBCL was significantly lower than that of CD5- DLBCL (t-test, P = 0.024). These data may indicate that the cell origin of CD5+ DLBCL is different from that of CD5- DLBCL. CD5 is not an activated antigen in DLBCL, but a specific marker of the B1 subset of the B cells, and de novo CD5+ DLBCL may therefore be derived from this unique subset.

Swollen cortical neurons in Creutzfeldt-Jakob disease contain a phosphorylated neurofilament epitope.

The distribution of swollen neurons and the presence of a phosphorylated neurofilament protein (NFP) epitope in these cells were studied in six cases of Creutzfeldt-Jakob disease (CJD). Swollen neurons are widely distributed in the cerebral cortex and are most abundant in the cingulate and parahippocampal gyri. They are more numerous in the panencephalopathic type of CJD than in the subacute spongiform encephalopathic type. A phosphorylated epitope of NFP was detected in the perikarya of swollen neurons by an immunocytochemical method using a series of monoclonal antibodies that distinguish phosphorylated and nonphosphorylated epitopes of NFP. This abnormal distribution of phosphorylated NFP epitopes indicates that the process of NFP phosphorylation is altered in neurons affected by CJD. This investigation, in accordance with previous studies, suggests that the abnormal post-translational modification of the neurofilament may play an important role in the pathogenesis of several neurodegenerative disorders.

Production of monoclonal antibodies against human erythropoietin and their use in the purification of human urinary erythropoietin.

Several murine monoclonal antibodies (MAbs) specific for human erythropoietin (HuEpo) were produced by hybridomas obtained from the fusion of murine myeloma cells, P3X63-Ag.8-653, with the splenocytes of mice immunized with recombinant human Epo (rHuEpo). Based on epitope analysis by a competitive binding assay, these MAbs could be classified into at least three groups: (1) 1E10, (2) 1H7, (3) 2D6, 3D6 and 3D8. In a sandwich enzyme-linked immunosorbent assay (ELISA), using these MAbs as the solid-phase antibodies, MAb-bound HuEpo was detected with rabbit anti-HuEpo sera. Some combinations of two different classes of MAbs, such as 1H7 and 3D8, were found to capture much more HuEpo than each MAb used individually. Urinary HuEpo (U-HuEpo) was highly purified from the urine of patients with severe aplastic anemia with about 50% final recovery using an immunoaffinity column on which a mixture of 1H7 and 3D8 was immobilized. The purified U-HuEpo had a specific activity of 77,340 U/mg in a radioimmunoassay (RIA) and of 76,673 U/mg using an in vivo bioassay.

The propensity to malignancy of dispermic heterozygous moles.

Complete hydatidiform moles may originate from either the fertilization of an empty egg by a haploid sperm followed by duplication (producing a monospermic, homozygous mole) or the fertilization of such an egg by two haploid sperms (producing a dispermic, heterozygous mole). This difference in the mechanism leading to the formation of complete moles raises the question of whether the risk of subsequent malignancy is influenced by the zygosity of the mole. We have compared the incidence of postmolar sequelae in patients with homozygous and heterozygous moles. Using chromosomal heteromorphisms, human lymphocyte antigen (HLA) and phosphoglucuromutase 1 (PGM1) polymorphisms, we established the androgenetic origin of complete mole in 84 of 91 cases. Homozygosity was confirmed in 51 moles, and we found ten heterozygous moles. Five of ten patients with heterozygous moles developed postmolar trophoblastic disease, whereas only two of the 51 patients with homozygous moles had postmolar trophoblastic disease (an additional five patients showed signs of degenerating residual trophoblasts). The XY sex chromosome constitution of the two in vitro choriocarcinoma cell lines examined here provides further evidence of the propensity to malignancy of heterozygous moles.

G(M3) inhibits murine MET-2 tumor invasion and growth.

G(M3) has some important roles in cell-to-cell interaction and has proved to have an optimal concentration for fibronectin mediated cell adhesion. G(M3) content in murine bladder tumor (MBT-2) assessed by thin-layer chromatography was similar to human invasive bladder tumor. From glycolipid composition also, MBT-2 is considered as an appropriate model for human invasive bladder tumor. Anti-tumor effect of locally administered G(M3) On MBT-2 tumor was investigated. MBT-2 cells were injected subcutaneously into the right hind limb of CH3/HeSlc female mice on day 1. Tumor bearing mice were randomly placed on day 8 into G(M3) treatment, G(D3) treament, sialic acid treament and control groups. G(M3) was administered between tumor and fascia at 10 mu g in 0.1 ml, 1 mu g in 0.1 ml from day 8 to day 20 every other day, 7 times in total. Control group was given 0.1 mi of saline. G(D3) group was given 12.5 mu g of G(D3), and sialic acid group 2.5 mu g of sialic acid. The relative growth rates of control group, G(M3) 1 mu g group, G(M3) 10 mu g group on day 22 were 139+/-74, 56+/-39, 22+/-14, respectively, and statistically significant among these three groups (Mann-Whitney's U test p<0.01). There were no significant difference between control and G(D3) or sialic acid group. All of the 15 control mice had muscle invasion, however, of the 19 G(M3) 10 mu g administered mice, only 4 had muscle invasion. The incidence of muscle invasion between these 2 groups was statistically significant in chi(2) test (p<0.001). Locally administered G(M3) inhibited both invasion and growth of MBT-2 tumor. This mechanism could be explained by an important role of G(M3) in cell adhesion mediated by integrin and fibronectin interaction. These results may be applied to antiadhesion therapy of human invasive bladder tumor.

Enhanced GM3 expression, associated with decreased invasiveness, is induced by brefeldin A in bladder cancer cells.

We reported previously that non-invasive bladder cancer expresses high level of GM3 ganglioside, whereas invasive tumors have low levels. Since glycosphingolipid synthesis in Golgi is modified greatly by a macrocyclic lactone isolated from fungi, brefeldin A (BFA), we studied effects of BFA on expression of glycosphingolipids and on invasiveness of bladder cancer cell lines. Only GM3 synthesis in invasive tumors was greatly enhanced upon treatment with BFA; synthesis of other glycosphingolipids with lacto-series type 2 or globo-series structure in both invasive and non-invasive tumors was not changed. Invasiveness of bladder cancer cells was greatly decreased in association with the great increase of GM3 synthesis induced by BFA treatment. Level of sialyl-Lex expressed in invasive cell line YTS1, which provides the adhesive property of the cells to E-selectin, was unchanged upon BFA treatment. All the bladder cancer cell lines, regardless of invasiveness, highly express tetraspanin CD9. GM3 has been implicated as a co-factor of CD9 in control of tumor cell motility. Down-regulation of CD9 is associated with metastatic properties of tumor cells and survival of patients with colonic cancer. Therefore, enhanced synthesis of GM3 induced by BFA, causing decrease of invasiveness in bladder cancer, is ascribable to the capability of GM3 to interconnect integrin with CD9, in analogy to colonic cancer and perhaps many other types of cancer.

Enzyme-linked immunosorbent assay detection of prostate-specific antigen messenger ribonucleic acid in prostate cancer.

OBJECTIVES: To develop a rapid, sensitive, reverse transcriptase-polymerase chain reaction (RT-PCR) prostate-specific antigen (PSA) messenger ribonucleic acid (mRNA) detection method by applying colorimetric enzyme-linked immunosorbent assay (ELISA). METHODS: Total RNA was extracted from 16 urogenital cancer cells (including PSA-producing LNCaP cells) from pelvic and inguinal lymph node aspiration biopsy samples from patients with prostate, bladder, and penile cancer, as well as from blood samples of 500 patients with urogenital cancer. We used rTth polymerase for RT and PCR. The RNA target was amplified by RT-PCR with dinitrophenyl-labeled primer. The PCR product was denatured and hybridized on a PSA-specific probe-coated microwell plate. RESULTS: In 1 6 cancer cell lines, only LNCaP cells expressed especially high PSA mRNA values, with an optical density (OD) greater than 3. In other cell lines, two testicular cells had relatively high ODs, 1.909 and 0.987, respectively. A high PSA mRNA value was obtained by fine needle aspiration from pelvic lymph node specimens of cytologically positive lymph nodes from patients with prostate cancer but not from patients with cytologically proved bladder or penile cancer. Sensitivity and specificity of fine needle aspiration samples were 70% and 100%, respectively. Blood tests obtained from patients with prostate cancer demonstrated high PSA mRNA values. CONCLUSIONS: The PSA mRNA RT-PCR ELISA method provides a sensitive photometric enzyme immunoassay for the detection of PSA mRNA, using nonradioactive techniques.

Inhibitory effects of ulinastatin on the production of cytokines: implications for the prevention of septicemic shock.

The study was designed to determine whether ulinastatin can be used as a biological response modifier for the prevention of septicemic shock. Monocytes from heparinized blood of three healthy volunteers were incubated with 0.125 or 1.25 U/ml of ulinastatin, and then endotoxin (Escherichia coli lipopolysaccharide) was added at concentrations of 0.1, 1.0, and 10.0 micrograms/ml. A dose-dependent increase in the production of tumor necrosis factor alpha, interleukin-1 alpha, and interleukin-1 beta was noted after endotoxin stimulation. Production of these cytokines was inhibited by the addition of ulinastatin in a dose-dependent manner. The results indicate that ulinastatin could be useful in the prevention of septicemic shock.

The effects of immune globulin on endotoxemia.

Ten patients (mean age, 40 years; 2 women) with endotoxemia received 2.5 gm of immune globulin daily for 4 days or 5 gm daily for 2 days. In all patients, plasma endotoxin levels decreased to normal levels (< or = 9.8 pg/ml) within a mean of 3.2 days after starting immune globulin treatment, and body temperatures decreased to < 37 degrees C within 4.5 days. In 10 antibiotic-treated (control) patients with endotoxemia who did not receive immune globulin, plasma endotoxin levels declined to normal levels in 6 and their body temperatures dropped to normal levels within 5.0 days; no changes in body temperature were noted in the 4 patients whose plasma endotoxin levels did not decrease.

Treatment of endotoxemia with low-dose intramuscular injections or oral administration of polymyxin B.

Thirty patients with sepsis received 50,000 U of polymyxin B intramuscularly per day (n = 22) or 3 million U orally per day (n = 8). Plasma endotoxin levels were measured by the Endospecy test after treating the plasma with a new perchloric acid method. Plasma endotoxin levels were reduced to normal values (less than 9.8 pg/ml) in all the injected patients within two days and in all the orally treated patients within three days. Clinical symptoms were also ameliorated. No treatment side effects were reported. It is concluded that polymyxin B is a safe and effective treatment against endotoxemia.

Evaluation of IPM/CS in gram-negative bacillus infections: use of an endotoxin-specific assay.

The subjects were 26 patients hospitalized with severe trauma or burns. Twice daily for seven to 14 days, 1 gm of IPM/CS (a 1:1 combination of imipenem and cilastatin sodium) was administered by intravenous drip infusion to each patient. Clinical outcome was rated excellent in nine patients, good in 12, and fair in five. Bacteria, isolated in 21 of the 26 patients, were eliminated in 18 and decreased in three. Mean endotoxin levels, assessed by the Endospecy method, were reduced from 167.8 pg/ml before treatment to 5.1 pg/ml after treatment. No treatment side effects were noted.