Intraperitoneal pharmacokinetics of vancomycin in patients on automated peritoneal dialysis

It is unclear if the pharmacokinetics of vancomycin are the same during automated peritoneal dialysis (APD), where cycler exchanges may affect the systemic, peritoneal, and urinary disposition of drug. We conducted a prospective pharmacokinetic study evaluating the pharmacokinetics of vancomycin in plasma, dialysis fluid, and urine in peritonitis‐negative patients on APD. Patients underwent four drug‐free exchanges with 1.5% or 2.5% dextrose following the initial dwell period. Plasma, dialysis fluid, and urine was collected over the course of 7 days for pharmacokinetic analysis. Four patients completed the study with no adverse events. Following a median (range) dwell of 14.6 (14.2–17.6 h), the mean (±SD) observed maximum plasma concentration was 28.7 ± 4.9 mg/L with a mean bioavailability of 98.5 ± 1.4% prior to starting the cycler. The overall mean total plasma clearance estimated from study start to completion was 7.6 ± 1.2 ml/min. Mean total clearance during the dialytic exchange was 13.6 ± 4.9 ml/min. In patients with residual renal function, the mean vancomycin renal clearance was 3.1 ± 1.5 ml/min, representing 21.4%–58.9% of the overall total plasma clearance during the study period. Despite the small sample size, this pilot study suggests that the dwell time has important implications for systemic vancomycin exposure, time to therapeutic plasma concentration, and dosing. Dose is driven by dwell time, whereas the cycler determines the dosing interval. Rapid exchanges from APD will determine the frequency of dosing rather than the adequacy of absorption when vancomycin is given in the peritoneum.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Vancomycin dosing in patients with peritonitis during automated peritoneal dialysis (APD) is empiric and extrapolated from studies in patients on continuous ambulatory peritoneal dialysis (CAPD). Extrapolation of pharmacokinetic data from CAPD to APD may result in substantial under‐ or overdosing due to rapid exchanges and longer dwell times. The impact of residual renal function on vancomycin pharmacokinetics is also unknown.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study assessed the absorption and disposition of vancomycin following an intraperitoneal dose. Disposition of vancomycin was assessed in plasma, dialysis fluid, and urine.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Drug‐dialysis fluid dwell times of up to 15 h achieves adequate therapeutic vancomycin concentrations in plasma. Rapid exchanges from APD increases vancomycin total systemic plasma clearance during the exchange period.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Drug‐dialysis fluid dwell time has direct influence on the systemic bioavailability and therapeutic concentration of vancomycin. Initial and maintenance vancomycin dosing regimens should account for the dwell time, dialytic and renal clearance, and microbial susceptibility.     

PDCD2 functions in cancer cell proliferation and predicts relapsed leukemia

PDCD2 is an evolutionarily conserved eukaryotic protein with unknown function. The Drosophila PDCD2 ortholog Zfrp8 has an essential function in fly hematopoiesis. Zfrp8 mutants exhibit marked lymph gland hyperplasia that results from increased proliferation of partially differentiated hemocytes, suggesting Zfrp8 may participate in cell growth. Based on the above observations we have focused on the role of PDCD2 in human cancer cell proliferation and hypothesized that aberrant PDCD2 expression may be characteristic of human malignancies. We report that PDCD2 is highly expressed in human acute leukemia cells as well as in normal hematopoietic progenitors. PDCD2 knockdown in cancer cells impairs their proliferation, but not viability relative to parental cells, supporting the notion that PDCD2 overexpression facilitates cancer cell growth. Prospective analysis of PDCD2 in acute leukemia patients indicates PDCD2 RNA expression correlates with disease status and is a significant predictor of clinical relapse. PDCD2’s role in cell proliferation and its high expression in human malignancies make it an attractive, novel potential molecular target for new anti-cancer therapies.     

Cutaneous nodular fasciitis with genetic analysis: a case series

Nodular fasciitis is a benign self‐limited myofibroblastic neoplasm, which usually involves the upper extremities and trunk of young patients. These tumors have been shown to harbor a translocation involving the MYH9 and USP6 genes, leading to overexpression of the latter. We report seven cases of nodular fasciitis with cutaneous presentations. All cases involved the dermis, with six involving the superficial subcutis, and one auricular tumor extending into cartilage. All cases showed USP6 rearrangement by fluorescence in situ hybridization; in two of three cases, the characteristic MYH9‐USP6 fusion was shown by RT‐PCR. All patients underwent conservative resection. Nodular fasciitis is an uncommon mesenchymal neoplasm that can occasionally present in superficial locations and is sometimes mistaken for a malignant process. Molecular testing can be useful to distinguish this entity from other cutaneous spindle cell tumors.     

Vector competence of Culex pipiens molestus (Diptera: Culicidae) from Taiwan for a sympatric strain of Japanese encephalitis virus

Laboratory strains of Culex pipiens molestus Forskal and Culex tritaeniorhynchus Giles from northern Taiwan were compared for their susceptibility to the Sanhsia MQ1-2 (SH) strain of Japanese encephalitis (JE) virus isolated from Taiwan. After feeding on a sweetened blood-virus mixture, viral titers in Cx. p. molestus during the 14-d incubation period ranged from a minimum of 2.9 log10PFU (plaque forming units) per mosquito on day 3 after ingestion to a maximum of 4.65 log10PFU at day 8 and in Cx. tritaeniorhynchus from 2.6 on day 10-5.18 log10PFU per mosquito on day 13. Although virus titer in Cx. p. molestus was lower than in Cx. tritaeniorhynchus at the end of the experiment, this difference was not statistically significant. The median infective dose (ID50) for Cx. p. molestus was 2.83 log10PFU and for Cx. tritaeniorhynchus was 1.02 log10PFU per mosquito, and this difference also was not significant. There also was no significant difference between the median infective dose for transmission (TID50) per mosquito for Cx. p. molestus (5.34 log10PFU) and Cx. tritaeniorhynchus (4.59 log10PFU). We concluded that Cx. p. molestus is an effective laboratory vector of JE virus.     

Secondary prevention of ischemic stroke with low dose acetylsalicylic acid

In order to evaluate the efficacy of low dose acetylsalicylic acid (ASA) for the secondary prevention of ischemic stroke, this cooperative multicenter clinical trial was conducted on a non-blind basis. Patients having a first transient ischemic attack (TIA), reversible ischemic neurological deficit (RIND) or completed ischemic stroke were eligible for this trial. A total of 590 patients including 47 cases of TIA, 23 cases of RIND and 520 cases of completed stroke entered this study. These patients were allocated by the time of admission to one of the following 5 trial regimens: (1) vasodilators having no known inhibitory effect on platelet function (control group), (2) dipyridamole (DP) 50 mg 3 times a day (DP group), (3) ASA 300 mg once a day (ASA 300 mg group), (4) ASA 300 mg once in combination with DP 50 mg 3 times a day (ASADP group), and (5) ASA 100 mg once a day (ASA1 group). No difference in effect between the control and DP groups was observed, nor between the ASA 300 mg and ASADP groups. Therefore, we combined the control and DP groups to make a non-ASA group, and joined the ASA 300 mg and ASADP groups to make an ASA3 group. The differences in the cumulative event-free rate appeared to be significant between the non-ASA group and the ASA3 group and also between the non-ASA group and the ASA1 group. But the frequency distribution of age, territory of stroke, diabetes mellitus, cardiac disease, hematological disease and hyperuricemia were significantly different among these 3 study groups. We thus included these covariates in the Cox's proportional hazard model to control their possible confounding effects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Laparoscopy in the diagnosis and management of ovarian cancer

Ninety-two laparoscopies were performed for diagnosis and follow-up on 83 patients with clinical diagnoses of ovarian cancer from May 1979 to May 1981. With laparoscopy about 10% of the cases were disproven; of suspicious cases only 53% were confirmed. Laparoscopy was very helpful in clarifying the clinical diagnosis of ovarian carcinoma. Laparoscopy for follow-up evaluation of treatment was done on 44 patients. Very early recurrence, which is very difficult to detect on clinical examination, was found with second-look laparoscopy. If few adhesions are present, laparoscopy can replace second-look exploration in the majority of cases of complete remission.