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At least 145 records · Page 8Linked to original sources
PubMed2003

Expression of the chemokine IP-10 (CXCL10) by hepatocytes in chronic hepatitis C virus infection correlates with histological severity and lobular inflammation.

The factors influencing lymphocyte trafficking to the liver lobule during chronic hepaititis C virus (HCV) infection are currently not well defined. Interferon-gamma-inducible protein 10 (IP-10), a chemokine that recruits activated T lymphocytes, has recently been shown by in situ hybridization to be expressed in the liver during chronic HCV infection. This study sought to define the cellular source of IP-10 in the liver by immunohistochemistry, to examine the expression of its receptor, CXCR3, on T lymphocytes isolated from blood and liver tissue, and to correlate IP-10 expression with the histological markers of inflammation and fibrosis. IP-10 was expressed by hepatocytes but not by other cell types within the liver, and the most intense immunoreactivity was evident in the areas of lobular inflammation. The IP-10 receptor was expressed on a significantly higher proportion of T lymphocytes in the liver compared with blood. CD8 T lymphocytes, which predominate in the liver lobule, were almost uniformly CXCR3-positive. The expression of IP-10 mRNA correlated with lobular necroinflammatory activity but not with inflammation or fibrosis in the portal tracts. These findings suggest that IP-10 may be induced by HCV within hepatocytes and may be important in the pathogenesis of chronic HCV infection, as recruitment of inflammatory cells into the lobule is an important predictor of disease progression.

Adult↗
PubMed2006

Human rhinovirus induces robust IP-10 release by monocytic cells, which is independent of viral replication but linked to type I interferon receptor ligation and STAT1 activation.

Human rhinovirus (HRV)-induced respiratory infections are associated with elevated levels of IFN-gamma-inducible protein 10 (IP-10), which is an enhancer of T lymphocyte chemotaxis and correlates with symptom severity and T lymphocyte number. Increased IP-10 expression is exhibited by airway epithelial cells following ex vivo HRV challenge and requires intracellular viral replication; however, there are conflicting reports regarding the necessity of type I IFN receptor ligation for IP-10 expression. Furthermore, the involvement of resident airway immune cells, predominantly bronchoalveolar macrophages, in contributing to HRV-stimulated IP-10 elaboration remains unclear. In this regard, our findings demonstrate that ex vivo exposure of human peripheral blood monocytes and bronchoalveolar macrophages (monocytic cells) to native or replication-defective HRV serotype 16 (HRV16) resulted in similarly robust levels of IP-10 release, which occurred in a time- and dose-dependent manner. Furthermore, HRV16 induced a significant increase in type I IFN (IFN-alpha) release and STAT1 phosphorylation in monocytes. Neutralization of the type I IFN receptor and inhibition of JAK or p38 kinase activity strongly attenuated HRV16-stimulated STAT1 phosphorylation and IP-10 release. Thus, this work supports a model, wherein HRV16-induced IP-10 release by monocytic cells is modulated via autocrine/paracrine action of type I IFNs and subsequent JAK/STAT pathway activity. Our findings demonstrating robust activation of monocytic cells in response to native and/or replication-defective HRV16 challenge represent the first evidence indicating a mechanistic disparity in the activation of macrophages when compared with epithelial cells and suggest that macrophages likely contribute to cytokine elaboration following HRV challenge in vivo.

Cell Communication↗
PubMed2001

Elevated serum IP-10 levels observed in type 1 diabetes.

OBJECTIVE: Although most patients with type 1 diabetes are considered to have T-cell-mediated autoimmune disease, a method of measuring of pancreatic beta-cell-specific T-cell function in cases of type 1 diabetes has yet to be established. Here, we focused on interferon-inducible protein-10 (IP-10), a chemokine that promotes the migration of activated T-helper 1 (Th1) cells and measured serum IP-10 levels in patients with human type 1 diabetes, which is regarded as a Th1-mediated disease. RESEARCH DESIGN AND METHODS: Serum samples were obtained from diabetic patients, and the levels of autoantibodies (GAD and insulinoma-associated protein-2 [IA-2]) and IP-10 were measured. Diabetic patients positive for either or both of the autoantibodies were classified as Ab+ type 1, and those negative for both were classified as Ab type 1. To evaluate islet antigen-specific responses, peripheral blood from patients stimulated with or without GAD was used, and intracellular cytokine staining for flowcytometry was performed. RESULTS: The Ab+ and Ab- type 1 groups both showed a significantly higher serum IP-10 level than the healthy subjects (P < 0.001 and P < 0.05, respectively), and the IP-10 level in the recent-onset Ab+ subgroup was significantly higher than that in the established (longstanding) Ab+ subgroup (P < 0.002). Furthermore, there was a significant positive correlation between the serum IP-10 level and the number of GAD-reactive gamma-interferon-producing CD4+ cells in the Ab+ type 1 group (P < 0.007). CONCLUSIONS: Our findings demonstrate that measurement of serum IP-10 concentrations is useful in patients with type 1 diabetes.

Adult↗
PubMed1999

Analysis of agonist function at fusion proteins between the IP prostanoid receptor and cognate, unnatural and chimaeric G-proteins.

Direct measures of G-protein activation based on guanine nucleotide exchange and hydrolysis are frequently impossible to monitor for receptors which interact predominantly with G(s)alpha. An isolated FLAG (Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Lys)-epitope-tagged human IP prostanoid receptor and fusion proteins generated between this form of the receptor and the alpha subunits of its cognate G-protein G(s), G(i1), a G-protein which it fails to activate in co-expression studies, and a chimaeric G(i1)-G(s)6 (a form of G(i1) in which the C-terminal six amino acids were replaced with the equivalent sequence of G(s)) were stably expressed in HEK293 cells. These were detected by [(3)H]ligand-binding studies and by immunoblotting with both an anti-FLAG antibody and with appropriate antisera to the G-proteins. Each construct displayed similar affinity to bind the agonist iloprost. Iloprost stimulated adenylate cyclase activity in clones expressing both IP prostanoid receptor and the IP prostanoid receptor-G(s)alpha fusion protein, and both constructs were shown to interact with and activate endogenously expressed G(s)alpha. Addition of iloprost to membranes of cells expressing the isolated receptor resulted in a small stimulation of high-affinity GTPase activity. Iloprost produced no stimulation of GTPase activity which could be attributed to the IP prostanoid receptor-G(i1)alpha fusion. However, the fusion proteins containing either G(s)alpha or G(i1)-G(s)6alpha produced substantially greater stimulation of GTPase activity than the isolated IP prostanoid receptor. Treatment of cells expressing the IP prostanoid receptor-G(i1)-G(s)6alpha fusion protein with a combination of cholera and pertussis toxins allowed direct measurement of agonist activation of the receptor-linked G-protein. Normalization of such results for levels of expression of the IP prostanoid receptor constructs demonstrated a 5-fold higher stimulation of GTPase activity when using the G(s)alpha-containing fusion protein and a 9-fold improvement when using the fusion protein containing G(i1)-G(s)6alpha to detect G-protein activation compared with expression of the isolated receptor.

Adenylate Cyclase Toxin↗
PubMed2005

Growth and cell viability of estradiol and IP-6 treated Hep-2 laryngeal carcinoma cells.

Inositol 6-phosphate (IP-6) has demonstrated novel anti-cancer activity using several different tumor models. IP-6, a phytoestrogen, has estrogen receptor (ER) binding capabilities that are not known to cause cellular proliferation in hormone sensitive cells. It is hypothesized that IP6 can induce competitive inhibition with estrogen for estrogenic binding sites on cancer cells resulting in decreased proliferation. In this experiment, Hep-2 cells were treated with Estradiol and IP-6 in a dose dependant manner for 24, 48, and 72 hours. They were analyzed for changes in number, protein concentrations, damage, and morphology. There was an increase in cell proliferation in Estradiol treated Hep-2 cells. Cells treated with IP-6 showed no change in cell proliferation in the 24 or 48-hour groups, but there was a decrease in number with the 72-hour group, particularly with the 1mM dose. Both the Estradiol and IP-6 treatments caused no membrane oxidation and the level of protein synthesis stayed consistent. The morphology showed small round to cuboidal, single cells with scant, dense, basophilic cytoplasm and hyperchromatic nuclei with smooth borders. Some cells showed anucleation and cellular degeneration. Although IP-6 is a phytoestrogen, the results show that affinity for estrogen binding sites on Hep-2 cells is greatly decreased. However, with time given increased concentrations, IP-6 can cause a decrease in the cellular proliferation of Hep-2 cells without initiating cellular apoptosis.

Antineoplastic Agents↗
PubMed2006

[Preliminary clinical results of a prospective study of IPS e.max Press- and Cerec ProCAD- partial coverage crowns].

UNLABELLED: It was the aim of this prospective clinical splitmouth investigation to evaluate the survival rate and long-term behavior of all-ceramic partial coverage restorations (PCR) on molars. Pressed ceramic (IPS e.max Press) and CAD/CAM made (ProCAD) PCR were compared. 80 vital molars of 25 patients were restored with all-ceramic PCR (40 IPS e.max Press* and 40 ProCAD*). All PCR were adhesively luted with a light-polymerizing composite (Syntac*/Tetric*) (*Ivoclar-Vivadent AG, Schaan, Liechtenstein). The ProCAD PCR were produced with Cerec 3 and Cerec Inlab CAD/CAM system (Sirona Dental Systems, Bensheim, Germany). IPS e.max Press PCR were heat-pressed following the lost-wax IPS-Empress method. Clinical recall was arranged in average 8, 14, 20 and 28 months after cementation of the restoration. PCR were classified by USPHS criteria. The prospective survival rate of ProCAD PCR was 97% and 100% for IPS e.max Press PCR after an observation period of 24 months. After fracture, one ProCAD restoration had to be replaced after nine months. The clinical accuracy of the marginal fit of ProCAD PCR and IPS e.max Press PCR was recorded "Alfa". Limitations were recognized with respect to the color matching of both types of PCR ("Bravo"). CONCLUSION: Within the limits of the present clinical results, the tested all-ceramic materials IPS e.max Press und ProCAD seem to be indicated for partial coverage restorations on molars.

Aluminum Silicates↗
PubMed1979

Chemotherapy for murine ovarian cancer: a rationale for ip therapy with adriamycin.

The metastatic spread of a trnasplantable murine ovarian cancer is similar to the spread of ovarian cancer in patients with advanced disease, making it a useful model to investigate novel experimental therapies. The ip inoculation of 10(6) tumor cells into C3HeB/FeJ mice leads to the formation of ascites, sub-diaphragmatic tumor deposits, intra-abdominal tumors, and death within 25 days. Adriamycin (ADR) was found to be an active agent against this murine ovarian cancer. The effects of ADR were dependent upon the route of administration. A single ip LD10 dose of ADR (5 mg/kg) administered 2 days after inoculation with 10(6) tumor cells produced long-term survival (greater than 60 days) in 70% of the mice. An iv LD10 dose had no effect on survival. The survival advantage of ip ADR (compared to the iv route) was found to be related to: (a) a greater suppression of DNA synthesis in the tumor; (b) a rapid penetration of ADR into the nuclei of ascites tumor cells and into sub-diaphragmatic tumor deposits; and (c) significantly higher levels of ADR in tumor cells following ip administration. The ip route may also be less cardiotoxic since the peak levels after an iv dose were three times greater than after an equal ip dose. If local toxicity does not prove to be a major problem, then ip ADR may be a useful mode of therapy in patients with intra-abdominal tumors.

Animals↗
PubMed1995

Cytokine loops involving interferon-gamma and IP-10, a cytokine chemotactic for CD4+ lymphocytes: an explanation for the epidermotropism of cutaneous T-cell lymphoma?

Human interferon-gamma (IFN-gamma)-inducible protein 10 (IP-10), a C-X-C chemokine, is secreted by IFN-gamma-stimulated keratinocytes and is chemotactic for CD4+ lymphocytes. We therefore investigated its role in the epidermotropism of cutaneous T-cell lymphoma (CTCL) that is known to express IFN-gamma mRNA in the epidermis and is characterized by an indolent course with multiple relapses that remain confined to the skin for many years. By injecting purified recombinant (r) IP-10 we generated a polyclonal rabbit antiserum that specifically recognized and neutralized rIP-10. With immunoperoxidase staining, IP-10 expression was limited to the basal epidermal keratinocytes of normal skin. In biopsies of CTCL lesions the expression of IP-10 was markedly increased and it extended to the suprabasal keratinocytes in 17 of 18 patients, but it was detectable only faintly in the dermal or epidermal lymphoid infiltrates in 2 of these 18 patients. In 1 patient who had matching biopsies performed before and after treatment, IP-10 was overexpressed before treatment, but was normally expressed in the posttreatment biopsy that showed resolution of the CTCL. Increased IP-10 expression was not detected in any of 4 patients with B-cell lymphoma involving the dermis. On the basis of these findings and a review of the literature, we propose that secretion of IFN-gamma by the lymphoid infiltrate in CTCL induces the epidermal keratinocytes to secrete IP-10 that, in turn, is chemotactic for CTCL, accounting for its epidermotropism. This model may be used as a basis for future investigations of the pathogenesis of CTCL.

Adult↗
PubMed2000

Conservation of localization patterns of IP(3) receptor type 1 in cerebellar Purkinje cells across vertebrate species.

The distribution of inositol 1,4,5-trisphosphate (IP(3)) receptor type 1 (IP(3)R1) protein was studied in the adult cerebella of six different vertebrate species, zebrafish, skate, claw frog, rat, hamster, and mouse. The receptor was found at high expression levels in Purkinje cells in all species examined using a subtype-specific polyclonal antiserum against IP(3)R1 and fluorescence immunocytochemistry. The immunoreactivity for IP(3)R1 was found intracellularly at high concentrations in dendrites and somata and at lower levels in axons of these cells. Despite the morphological and functional differences of the cerebella the staining patterns of IP(3)R1 labeling in Purkinje cells was preserved. This is notable because the cerebella were taken from organisms representing a large segment of vertebrate phylogenetic development. The high expression levels of IP(3)R1 in Purkinje cells were found independent of the degree of the formation of fissures and folia and of the degree of branching of Purkinje cell dendrites. The conservation of cerebellar structures not only at the cellular level but more importantly at the molecular level suggests that identical intracellular calcium signaling mechanisms are used in a number of species that represent different areas of phylogenetic development and specialization.

Animals↗
PubMed1998

Contribution of the CXC chemokines IP-10 and Mig to the antitumor effects of IL-12.

The mechanisms by which interleukin-12 (IL-12) exerts antitumor effects have been difficult to dissect. In this study, we examined the potential contribution of the chemokines interferon-gamma-inducible protein-10 (IP-10) and Mig to the antitumor effects of IL-12. Using an athymic mouse model, local inoculations with IL-12 consistently produced tumor size reductions associated with characteristic tumor necrosis and vascular damage. These effects were indistinguishable from those produced by IP-10 or Mig injected locally in the same tumor model. Local and systemic treatment with IL-12 was associated with expression of the interferon-gamma (IFN-gamma), IP-10, and Mig genes and proteins in the tumor. Levels of IP-10 and Mig expression in the tumor, the liver, and the kidney were inversely correlated with tumor size. Administration in vivo of neutralizing antibodies to IP-10 and Mig reduced substantially the antitumor effects of IL-12 inoculated locally into the tumors. These results support the notion that IP-10 and Mig contribute to the antitumor effects of IL-12 through their inhibitory effects on tumor vasculature.

Animals↗
PubMed2005

Expression of the interferon-inducible chemokine IP-10 (CXCL10), a chemokine with proposed anti-neoplastic functions, in Hodgkin lymphoma and nasopharyngeal carcinoma.

Hodgkin lymphoma (HL) and nasopharyngeal carcinoma (NPC) are characterized by their association with Epstein-Barr virus (EBV) and an abundant infiltrate of reactive lymphoid cells. The presence of this lymphoid stroma may influence the effect of anti-viral immunotherapy. The interferon-inducible chemokine IP-10 has anti-neoplastic effects in several model systems mediated by T-cells expressing the CXCR3 chemokine receptor. Using in situ hybridization, it is shown that IP-10 is expressed in neoplastic cells of HL and correlates both with the mixed cellularity histotype and with EBV infection. IP-10 expression was also detected in tumour cells of most NPCs as well as in EBV-negative squamous cell carcinomas of the tongue. Thus, in carcinomas, IP-10 expression showed no correlation with EBV infection. Numerous CXCR3-positive lymphocytes were detected in the lymphoid stroma of HL and NPC, raising the possibility of a Th1-predominant immune response in these cases. In view of the proposed anti-neoplastic functions of IP-10 and CXCR3-positive lymphocytes, these findings are unexpected and raise the possibility that endogenous IP-10 expression in the context of human tumours may not exert the anti-tumour effects ascribed to it by in vitro experiments.

Animals↗
PubMed2002

Vascular endothelial growth factor induces IP-10 chemokine expression.

We have previously shown that intracavernous injection of vascular endothelial growth factor (VEGF) improved the recovery of erectile function in an arteriogenic impotence rat mode. We wished to identify genes that are affected by VEGF treatment in the penis. Specifically we examined the induction of IP-10 chemokine. Male rats were subjected to pudendal arterial ligation or sham operation. They were then treated with intracavernous injection of 4 microg of VEGF in phosphate-buffered saline (PBS) or PBS alone. At 6 and 24 h after treatment, the erectile tissue was then harvested for RNA isolation. The isolated RNA was used for microarray and RT-PCR analyses. Cultured rat cavernous smooth muscle cells (CSMC) were treated with VEGF and then subjected to RT-PCR analysis. Cultured human CSMC were treated with VEGF and then subjected to ELISA analysis. Microarray analysis detected IP-10 as an abundantly induced message in 6-h VEGF-treated tissues. This was further confirmed by RT-PCR analysis. Using cultured rat CSMC, induction of IP-10 mRNA was detectable in 1 and 2 h, but not 24 h, VEGF-treated cells. Induction of IP-10 at the protein level was observed with cultured human CSMC. Secretion of IP-10 into culture medium peaked at 4 h after treatment of human CSMC with 10 ng/ml of VEGF. Optimal VEGF dosage for IP-10 induction was 50 ng/ml when assayed with cells that were treated for 8 h.

Animals↗
PubMed1980

Purification and characterization of the estrogen-induced protein (IP) of the rat uterus.

One of the earliest responses of the rat uterus to estrogen is increased synthesis of a specific cytosol protein (IP). This synthesis is detectable within 40 min and is dependent on an even earlier actinomycin D-sensitive function. IP has now been purified to homogeneity as determined by SDS polyacrylamide gel electrophoresis (SDS PAGE). The procedure was complicated by a tendency of the more homogeneous and concentrated material to aggregate. Purification consisted of sequential chromatography, in the presence of 0.1% triton X-100, via DEAE-cellulose (2x), hydroxylapatite and agarose-acrylamide. These were followed by preparative PAGE and finally SDS PAGE. Molecular weight determination by Ferguson plot analysis yielded an apparent molecular weight of 45 000. On final SDS PAGE, the material consisted of two major bands: the 45 000 molecular weight IP band and a band with an estimated molecular weight of 80 000. This second band displayed an elevated synthesis in E2-stimulated uteri similar to IP and appeared to consist of some form of aggregated IP. Carbohydrate determination on SDS gels using periodic acid-Schiff (PAS) stain was negative. Co-purification of labeled cytosol proteins from uteri of control and E2-stimulated rats revealed that IP is synthesized to some extent in the unstimulated animal as well as the stimulated.

Animals↗
PubMed1982

A silicone-nylon laminated dressing (IP-758) for closure of excised or débrided burn wounds.

A synthetic dressing (IP-758) consisting of a silicone membrane with a laminated layer of nylon fabric was evaluated in patients as a substitute for biological materials to cover excised areas of burn wounds. During a 3-day interval, the tissue developed a tightly adherent bond to the synthetic dressing. The IP-758 conformed to irregularly-shaped regions and stretched with the movements of the wound surface. Seventeen burned children from 3 to 12 years of age and 1 adult are included in this study. In 12 cases, the mean area covered with the synthetic ranged from approximately 39 to 118 cm2. The average dressing remained in place for 3 days and was replaced once. Microbiological sampling (wet swab technique) of the area under the IP-758 after application of second dressing was compared with open control sites treated with topical antibiotics. The results with Staphylococcus aureus, a frequent contaminant, were similar for the two test areas. The IP-758 site in 6 patients contained an average of 10 3 S. aureus per swab test. Immediately following removal of the adherent IP-758 and control of local bleeding, the wounds in most patients provided excellent sites for autografts. The IP-758 dressing is well-tolerated, elastic and adherent to the burn wound permitting maturation of the wound to readily accept autografts.

Adult↗
PubMed2005

Effects of gap junction to Ca(2+) and to IP(3) on the synchronization of intercellular calcium oscillations in hepatocytes.

The frequency of free cytosolic calcium concentration ([Ca(2+)]) oscillations elicited by a given agonist concentration differs between individual hepatocytes. However, in multicellular systems of rat hepatocytes and even in the intact liver, [Ca(2+)] oscillations are synchronized and highly coordinated. In this paper, we have investigated theoretically the gap junction permeable to calcium and to IP(3) on intercellular synchronization by means of a mathematical model, respectively. It is shown that gap junction permeable to calcium and to IP(3) are effective on synchronizing calcium oscillations in coupled hepatocytes. Our theoretical results are similar either for the case of Ca(2+) acting as coordinating messenger or for the case of IP(3) as coordinating messenger. There exists an optimal coupling strength for a pair of connected hepatocytes. Appropriate coupling strength and IP(3) level can induce various harmonic locking of intercellular [Ca(2+)] oscillations. Furthermore, a phase diagram in two-dimensional parameter space of the coupling strength and IP(3) level (or the velocity of IP(3) synthesis) has been predicted, in which the synchronization region is similar to Arnol'd tongue.

Animals↗
PubMed2000

Identification of type 1 IP(3) receptors in the rat kidney and their modulation by immobilization stress.

Inositol 1,4,5-trisphosphate receptor (IP(3)-receptor) is a calcium channel, transporting calcium from intracellular stores to the cytoplasm. In kidney, IP(3)-receptors are involved in the signal transduction of various hormones. In our work we studied the effect of immobilization stress on the IP(3)-receptor's protein content in renal cortex and the medulla of normotensive and hypertensive rats. We detected both mRNA and type 1 IP(3)-receptor protein in medulla, but not in renal cortex. We found that this receptor was approximately twice as abundant in normotensive as in genetically hypertensive rat kidney. Immobilization stress decreased the amount of type 1 IP(3)-receptor in the renal medulla of normotensive rats approximately five times, while no effect due to single and/or repeated stress was observed in the renal medulla of spontaneously hypertensive rats. The results indicate that expression of type 1 IP(3)-receptor in renal medulla is modulated by hypertension and immobilization stress.

Alternative Splicing↗
PubMed2000

Inhibition by diallyl trisulfide, a garlic component, of intracellular Ca(2+) mobilization without affecting inositol-1,4, 5-trisphosphate (IP(3)) formation in activated platelets.

Garlic has been used in herbal medicine for thousands of years. Some reports have shown that garlic has protective effects against atherosclerosis and inhibits platelet function. In this study, we investigated the mechanism by which diallyl trisulfide (DT), a component of garlic, inhibits platelet function. DT inhibited platelet aggregation and Ca(2+) mobilization in a concentration-dependent manner without increasing intracellular cyclic AMP and cyclic GMP. DT also had no inhibitory effects on thromboxane A(2) (TXA(2)) production in cell-free systems. Collagen-related peptide (CRP)-induced Ca(2+) mobilization is regulated by phospholipase C-gamma2 (PLC-gamma2) activation. We evaluated the effect of DT on tyrosine phosphorylation of PLC-gamma2 and the production of inositol-1,4,5-trisphosphate (IP(3)). DT at concentrations that inhibited platelet aggregation and Ca(2+) mobilization had no effects on tyrosine phosphorylation of PLC-gamma2 or on the formation of IP(3) induced by CRP. Similar results were obtained with thrombin-induced platelet activation. DT inhibited platelet aggregation and Ca(2+) mobilization induced by thrombin without affecting the production of IP(3.) We then evaluated the effect of DT on the binding of IP(3) to its receptor. DT at high concentrations partially blocked the binding of IP(3) to its receptor. Taken together, our findings suggest that the agent suppresses Ca(2+) mobilization at a step distal to IP(3) formation. DT may provide a good tool for investigating Ca(2+) mobilization.

Allyl Compounds↗
PubMed1988

Intraperitoneal (IP) vancomycin therapy for CAPD peritonitis--a prospective, randomized comparison of intermittent v continuous therapy.

The use of intraperitoneal (IP) vancomycin as initial, single agent therapy for gram positive and "no organism" continuous ambulatory peritoneal dialysis (CAPD) peritonitis is described, comparing continuous and intermittent administration schedules. "Continuous" therapy consisted of an IP 1-g loading dose of vancomycin followed by 30 mg/L dialysate effluent. "Intermittent" therapy consisted of 2 IP doses of 30 mg vancomycin/kg body weight--the initial dose delivered at diagnosis and the second dose 1 week later. All patients presenting with peritonitis (n = 90) were randomized to receive either continuous or intermittent vancomycin therapy. Patients in whom gram negative organisms and fungi were identified by microscopy and culture were transferred to therapy with a more appropriate antibiotic (n = 39). In the remainder (n = 51), CAPD peritonitis was treated solely with vancomycin (continuous, n = 21; intermittent, n = 30). Clinical resolution was seen in all patients, requiring a mean of 3.2 days for macroscopic clearing of dialysate effluent. Recurrence of peritonitis within 1 month of cessation of therapy was unusual and did not vary between treatment protocols (4/21 v 3/30; P = NS). There were no differences in observed side effects. Thus, IP vancomycin proved to be a useful single agent therapy for gram positive and no organism CAPD peritonitis. Therapy with two IP doses was effective and as safe as continuous IP vancomycin therapy, and therefore should replace other vancomycin administration schedules in the treatment of CAPD peritonitis.

Drug Administration Schedule↗