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PubMed1995

Unique DNA repair property of an ultraviolet-sensitive (radC) mutant of Dictyostelium discoideum.

Dictyostelium discoideum is an organism that shows higher UV resistance than other organisms, such as Escherichia coli and human cultured cells. We examined the removal of cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts from DNA in the radC mutant and the wild-type strain using an enzyme-linked immunosorbent assay with monoclonal antibodies. Wild-type cells excised more than 90% of both CPD and 6-4 photoproducts within 4 h. Dictyostelium discoideum appeared to have a special repair system, because 6-4 photoproducts were repaired faster than CPD in E. coli and human cultured cells. In radC mutant cells, although only 50% of CPD were excised from DNA within 8 h, effective removal of 6-4 photoproducts (80% in 8 h) was observed. Excision repair-deficient mutants generally cannot remove both CPD and 6-4 photoproducts. Though the radC mutant shows deficient excision repair, it can remove 6-4 photoproducts to a moderate degree. These results suggest that D. discoideum has two kinds of repair systems, one mainly for CPD and the other for 6-4 photoproducts, and that the radC mutant has a defect mainly in the repair enzyme for CPD.

Animals↗
PubMed1998

Stability of cephalosporin prodrug esters in human intestinal juice: implications for oral bioavailability.

The levels of degradation of cefetamet pivoxil (CAT), cefuroxime axetil (CAE), and cefpodoxime proxetil (CPD) in 0.6 M phosphate buffer (pH 7.4) and human intestinal juice (pH 7.4) at 37 degreesC over 24 h were compared. Significant differences in the time courses of degradation and in the patterns of degradation products were observed. (i) The relative proportions of the Delta2- and Delta3-cephalosporins were roughly reversed in the two incubation media. In phosphate buffer, the major degradation product was the Delta2-cephalosporin (CAT = 61%; CAE = 74%; CPD = 85%), while in intestinal juice it was the Delta3-cephalosporin (CAT = 86%; CAE = 75%; CPD = 87%). (ii) Generally, the degradation of the prodrug esters progressed faster in intestinal juice than in phosphate buffer (e.g., for CAT the half-lives [t1/2s] were 0.78 and 4.3 h, respectively). (iii) The two diastereoisomers of CAE and CPD were degraded at different rates in intestinal juice (for the CAE diasteroisomers, t1/2s = 0.37 and 0.93 h; for the CPD diastereoisomers, t1/2s = 0.18 and 0.98 h) but were degraded at similar rates in phosphate buffer (for the CAE diastereoisomers, t1/2 = 1.6 h; for the CPD t1/2 diastereoisomers, = 2.2 h). It is concluded that (i) the Delta2 isomerization does not significantly affect the bioavailability of prodrug esters since enzymatic hydrolysis in the intestinal fluid proceeds mainly to the active Delta3-cephalosporin and (ii) the high degree of stereoselectivity of the enzymatic ester hydrolysis should make it possible to increase the bioavailabilities of certain prodrug esters (CAE, CPD) by using the more stable diasterioisomer.

Administration, Oral↗
PubMed2000

Baroreflexes prevent neurally induced sodium retention in angiotensin hypertension.

Recent studies indicate that renal sympathetic nerve activity is chronically suppressed during ANG II hypertension. To determine whether cardiopulmonary reflexes and/or arterial baroreflexes mediate this chronic renal sympathoinhibition, experiments were conducted in conscious dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-h urine collection from denervated (Den) and innervated (Inn) kidneys. Dogs were studied 1) intact, 2) after thoracic vagal stripping to eliminate afferents from cardiopulmonary and aortic receptors [cardiopulmonary denervation (CPD)], and 3) after subsequent denervation of the carotid sinuses to achieve CPD plus complete sinoaortic denervation (CPD + SAD). After control measurements, ANG II was infused for 5 days at a rate of 5 ng. kg(-1). min(-1). In the intact state, 24-h control values for mean arterial pressure (MAP) and the ratio for urinary sodium excretion from Den and Inn kidneys (Den/Inn) were 98 +/- 4 mmHg and 1.04 +/- 0.04, respectively. ANG II caused sodium retention and a sustained increase in MAP of 30-35 mmHg. Throughout ANG II infusion, there was a greater rate of sodium excretion from Inn vs. Den kidneys (day 5 Den/Inn sodium = 0.51 +/- 0.05), indicating chronic suppression of renal sympathetic nerve activity. CPD and CPD + SAD had little or no influence on baseline values for either MAP or the Den/Inn sodium, nor did they alter the severity of ANG II hypertension. However, CPD totally abolished the fall in the Den/Inn sodium in response to ANG II. Furthermore, after CPD + SAD, there was a lower, rather than a higher, rate of sodium excretion from Inn vs. Den kidneys during ANG II infusion (day 5 Den/Inn sodium = 2.02 +/- 0.14). These data suggest that cardiac and/or arterial baroreflexes chronically inhibit renal sympathetic nerve activity during ANG II hypertension and that in the absence of these reflexes, ANG II has sustained renal sympathoexcitatory effects.

Angiotensin II↗
PubMed2000

Assay of DNA photolyase activity in spinach leaves in relation to cell compartmentation-evidence for lack of DNA photolyase in chloroplasts.

Spinach cyclobutane pyrimidine dimer (CPD)-specific DNA photolyase was successfully detected in leaf extracts by an assay system for plant photolyase using an improved enzyme-linked immunosorbent assay (ELISA) which was newly introduced by novel horseradish peroxidase (HRP)-linked CPD specific monoclonal antibodies. The assay system includes two main steps: a photorepair reaction of CPD introduced in substrate DNA and measurement of CPD remained after the photorepair by the improved ELISA. When CPD- induced salmon sperm DNA was used as a substrate, high CPD-photolyase activities were observed in the enzyme fraction prepared from whole spinach leaf extracts, but not from chloroplast extracts. This strongly suggests that spinach CPD-specific photolyases are localized in cell compartments other than chloroplasts.

Animals↗
PubMedDate not supplied

Continuing professional development in pharmacy.

OBJECTIVE: To summarize a resource document that explains the concept and components of continuing professional development (CPD) for pharmacists, describes some of the drivers behind the reevaluation of current systems of continuing pharmacy education (CE), defines relevant terms, and outlines some experiences with CPD in selected countries that have already adopted the model. SUMMARY: CPD is an approach to lifelong learning being discussed as a potential model for pharmacists in the United States. CPD does not replace CE, but quality-assured CE is an essential component of CPD. Evidence is mounting, however, that traditional methods of CE do not adequately meet the life-long learning and professional development needs of health care professionals (HCPs) and are not always successful in affecting practice behavior and improving patient outcomes. The Institute of Medicine has concluded that the education and training of HCPs is in need of major overhaul. CPD, which is based on sound principles and adopts educational strategies that have been shown to be effective, potentially offers a quality improvement to the current systems for pharmacist CE. CONCLUSION: Interest in and support for the concept of CPD is growing. Case studies of successful implementation in the United States and other countries now exist. Further discussion on the implications of widespread implementation for pharmacists in the United States is needed.

Education, Pharmacy, Continuing↗
PubMed2002

Spatial-frequency-tuned mechanisms of the red-green channel estimated by oblique masking.

The sustained spatial-frequency-tuned (SF-tuned) mechanisms of nonoriented units were examined by means of orthogonal masking for the Red-Green (R-G) color channel, and those of oriented units by oblique masking for the achromatic channel but not for the color channels. An oblique-masking technique minimizes the artifacts that are due to spatial phase effects, local cues, spatial beats, spatial probability summation, and changing criteria. Therefore the spatial characteristics of the R-G color channel are now investigated by an oblique-masking technique and linked with my paper on orthogonal masking [J. Opt. Soc. Am. A 15, 1 (1998)]. The R-G channel was defined by the minimum-flicker and hue-cancellation techniques. A color monitor system was used to generate spatially localized (D6) vertical color test patterns [0.063-8 cycles per degree (cpd)] and sinusoidal oblique color masks (0.031-16 cpd, 1.2-60% contrasts). Color contrast sensitivity functions (CSFs), threshold elevation (TE) versus mask SF (TvSF) curves, and TE versus mask contrast (TvC) curves were measured by the method of constant stimuli with a two-interval forced-choice technique by using Powell's achromatizing lens under sustained (Gaussian, 2-s-duration) conditions. Results show the following: (1) The color CSF is a low-pass function of SF with average half-height SF of 0.7 cpd and cutoff SF of 14 cpd with the use of a color-detection criterion. (2) TvSF curves are broadly bandpass and fall into five groups, peaking at approximately 0.13, 0.5, 2, 4, and 8 cpd. The root-mean-square cone-color CSF is 3.8-5.4 times the stimulus-color CSF. (3) A "crowding effect" similar to that of the TvSF curves of the achromatic channel was also found, but the TvSF curves of the R-G channel are not sharply peaked, similar to the result for orthogonal masking. Data analysis led to the following conclusions: (1) A simple multiple-mechanism model yields one low-pass color mechanism (with average half-height SF of 0.54 cpd) and five bandpass SF-tuned color mechanisms; these six mechanisms are necessary to explain the CSF, TvSF, and TvC data simultaneously. (2) The bandpass mechanisms peaked at approximately 0.13, 0.5, 2, 4, and 8 cpd with average full bandwidths at half-heights of 3.6, 3.2, 2.1, 1.2, and 1.3 octaves, respectively. (3) Since oblique-masking color mechanisms (unlike achromatic oriented mechanisms) have broad orientation tuning under sustained conditions and there is a significant orthogonal masking, the oblique-masking color mechanisms may have contributions from both oriented and nonoriented units. (4) The high degree of similarity between the SF-tuned filters of mechanisms derived from oblique- and orthogonal-masking data suggests that most of the chromatic SF tuning is already accomplished by nonoriented units. (5) The quality of the fit to oblique- and orthogonal-masking data combined dropped enough to reject the hypothesis that the former taps the performance of only the same nonoriented mechanisms as those by the latter. Adding gain parameters that reduce the TEs for orthogonal masking gave a better fit, suggesting that orientation gains are one of the factors involved in the transformation of information from nonoriented to oriented mechanisms. However, the fit was still worse than that for oblique-(6) Since masking-alone or orthogonal-masking-alone data, suggesting that more factors may be involved. primate parvo lateral geniculate nucleus (pLGN) units behave in a fairly linear manner, the color contrast nonlinearity (which follows the linear filter) of a mechanism may be post-pLGN.

Color Perception↗
PubMed1996

Noninvasive assessment of right heart function by 81mKr equilibrium radionuclide ventriculography in chronic pulmonary diseases.

Noninvasive multigated equilibrium radionuclide ventriculography with krypton-81m (81mKr) was used to assess right heart relaxation in patients with chronic pulmonary diseases (CPD). The subjects consisted of 30 patients with CPD and 8 patients free of cardiopulmonary diseases admitted to our department. A region of interest (ROI) was selected on both the right atrium (RA) and right ventricle (RV). A time activity curve was obtained for each ROI. As a diastolic index of the right heart performance, the right atrial early emptying rate (RAER) was obtained from the right atrial time activity curve, while the right ventricular rapid filling rate (RVRFR) was obtained from the right ventricular time activity curve. The mean RAER was significantly lower in CPD patients compared with the control (CPD, 9.5 +/- 4.5; control, 16 +/- 3.4%/100 ms). Similarly, the mean RVRFR was significantly lower in CPD patients compared with the control (CPD, 27.3 +/- 9.9; control, 34 +/- 8.5%/100 ms). A strong negative correlation was noted between the mean pulmonary arterial pressure (mPAP) and RAER (r = -0.77; p < 0.001) and between the mPAP and the RVRFR (r = -0.63; p < 0.001). Our results suggest that RAER and RVRFR measured by 81mKr are clinically useful in the noninvasive assessment of right heart relaxation in patients with CPD.

Adult↗
PubMed2003

Cluster C personality disorder and recovery from major depression: 24-month prospective follow-up.

We investigated whether Cluster C personality disorder (CPD) is associated with recovery from depression. Changes in symptom scales in 30 patients with MD and CPD were compared with changes in 60 patients with MD alone over a 24-month follow-up period. Recovery of patients with MD and comorbid CPD was inferior to recovery of those with MD alone based on the Hamilton and Beck Depression Inventory (BDI) scales, and the SCL-90 total score. Only 18% of those with MD alone but 47% of those with CPD and MD met the criteria for major depression at the end of the 24-month follow-up. Multiple logistic regression analyses revealed an independent association between the lack of recovery (BDI score > 9 at 24 months) and the presence of CPD (OR 4.9, 95% CI 1.5-16.0). Moreover, the presence of CPD associated with the presence of major depression at 24 months (OR 4.2, 95% CI 1.4-12.2). The presence of CPD hinders the alleviation of depressive symptoms in major depression.

Adult↗
PubMed2005

qUVR-10, a major quantitative trait locus for ultraviolet-B resistance in rice, encodes cyclobutane pyrimidine dimer photolyase.

Rice qUVR-10, a quantitative trait locus (QTL) for ultraviolet-B (UVB) resistance on chromosome 10, was cloned by map-based strategy. It was detected in backcross inbred lines (BILs) derived from a cross between the japonica variety Nipponbare (UV resistant) and the indica variety Kasalath (UV sensitive). Plants homozygous for the Nipponbare allele at the qUVR-10 locus were more resistant to UVB compared with the Kasalath allele. High-resolution mapping using 1850 F(2) plants enabled us to delimit qUVR-10 to a <27-kb genomic region. We identified a gene encoding the cyclobutane pyrimidine dimer (CPD) photolyase in this region. Activity of CPD photorepair in Nipponbare was higher than that of Kasalath and nearly isogenic with qUVR-10 [NIL(qUVR-10)], suggesting that the CPD photolyase of Kasalath was defective. We introduced a genomic fragment containing the CPD photolyase gene of Nipponbare to NIL(qUVR-10). Transgenic plants showed the same level of resistance as Nipponbare did, indicating that the qUVR-10 encoded the CPD photolyase. Comparison of the qUVR-10 sequence in the Nipponbare and Kasalath alleles revealed one probable candidate for the functional nucleotide polymorphism. It was indicated that single-base substitution in the CPD photolyase gene caused the alteration of activity of CPD photorepair and UVB resistance. Furthermore, we were able to develop a UV-hyperresistant plant by overexpression of the photolyase gene.

Base Sequence↗
PubMed2003

Ultraviolet (280-400 nm)-induced DNA damage in the eggs and larvae of Calanus finmarchicus G. (Copepoda) and Atlantic cod (Gadus morhua).

In previous work, we evaluated the effects of ultraviolet (UV = 280-400 nm) radiation on the early life stages of a planktonic Calanoid copepod (Calanus finmarchicus Gunnerus) and of Atlantic cod (Gadus morhua). Both are key species in North Atlantic food webs. To further describe the potential impacts of UV exposure on the early life stages of these two species, we measured the wavelength-specific DNA damage (cyclobutane pyrimidine dimer [CPD] formation per megabase of DNA) induced under controlled experimental exposure to UV radiation. UV-induced DNA damage in C. finmarchicus and cod eggs was highest in the UV-B exposure treatments. Under the same spectral exposures, CPD loads in C. finmarchicus eggs were higher than those in cod eggs, and for both C. finmarchicus and cod embryos, CPD loads were generally lower in eggs than in larvae. Biological weighting functions (BWF) and exposure response curves that explain most of the variability in CPD production were derived from these data. Comparison of the BWF revealed significant differences in sensitivity to UV-B: C. finmarchicus is more sensitive than cod, and larvae are more sensitive than eggs. This is consistent with the raw CPD values. Shapes of the BWF were similar to each other and to a quantitative action spectrum for damage to T7 bacteriophage DNA that is unshielded by cellular material. The strong similarities in the shapes of the weighting functions are not consistent with photoprotection by UV-absorbing compounds, which would generate features in BWF corresponding to absorption bands. The BWF reported in this study were applied to assess the mortality that would result from accumulation of a given CPD load: for both C. finmarchicus and cod eggs, an increased load of 10 CPD Mb(-1) of DNA due to UV exposure would result in approximately 10% mortality.

Animals↗
PubMed2004

A novel glucagon receptor antagonist inhibits glucagon-mediated biological effects.

Glucagon maintains glucose homeostasis during the fasting state by promoting hepatic gluconeogenesis and glycogenolysis. Hyperglucagonemia and/or an elevated glucagon-to-insulin ratio have been reported in diabetic patients and animals. Antagonizing the glucagon receptor is expected to result in reduced hepatic glucose overproduction, leading to overall glycemic control. Here we report the discovery and characterization of compound 1 (Cpd 1), a compound that inhibits binding of 125I-labeled glucagon to the human glucagon receptor with a half-maximal inhibitory concentration value of 181 +/- 10 nmol/l. In CHO cells overexpressing the human glucagon receptor, Cpd 1 increased the half-maximal effect for glucagon stimulation of adenylyl cyclase with a KDB of 81 +/- 11 nmol/l. In addition, Cpd 1 blocked glucagon-mediated glycogenolysis in primary human hepatocytes. In contrast, a structurally related analog (Cpd 2) was not effective in blocking glucagon-mediated biological effects. Real-time measurement of glycogen synthesis and breakdown in perfused mouse liver showed that Cpd 1 is capable of blocking glucagon-induced glycogenolysis in a dosage-dependent manner. Finally, when dosed in humanized mice, Cpd 1 blocked the rise of glucose levels observed after intraperitoneal administration of exogenous glucagon. Taken together, these data suggest that Cpd 1 is a potent glucagon receptor antagonist that has the capability to block the effects of glucagon in vivo.

Adenylyl Cyclases↗
PubMed1989

Chlorophyll derivatives--a new photosensitizer for photodynamic therapy of cancer in mice.

The in vivo photosensitizing efficacy of chlorophyll derivatives (CpD), which had been developed as a new photosensitizer, was compared with that of hematoporphyrin derivatives (HpD). A murine tumor model implanted subcutaneously with S-180 cells on the abdomen was used. The CpD or HpD was administered by intratumoral injection, and light of appropriate wavelength was irradiated on the tumor areas for 10 minutes at 1h and 24h or 24h and 48h after the injection of photosensitizer. When CpD was injected, the early irradiation group (1h and 24h) showed a 100% tumor cure rate; however, the late irradiation group (24h and 48h) showed a 60% tumor cure rate (p less than 0.01). This showed that the early irradiation with light after injection of CpD was an important factor for obtaining better results. With HpD, there was no difference in tumor cure rate between early (1h and 24h, 80%) and late irradiation (24h and 48h, 80%) groups. Thus, in early irradiation groups, the tumor cure rate using CpD (100%) was superior to that of HpD (80%) (p less than 0.05). However, in late irradiation groups, the tumor cure rate using CpD (60%) was inferior to that of HpD (80%), but this difference was not statistically significant (p greater than 0.1). Pathologic sections of these tumors were made before treatment and 48h and 3 weeks after treatment. These showed geographic necrosis at 48h after treatment and no viable tumor tissue at 3 weeks after treatment. Our results showed that CpD was as effective as HpD as a photosensitizer for in vivo photodynamic therapy.

Abdomen↗
PubMed2004

Effects of herbal compound 861 on human hepatic stellate cell proliferation and activation.

AIM: To investigate the effects of herbal compound 861 (Cpd 861) on cell proliferation in human hepatic stellate cells (LX-2) and human hepatocellular liver carcinoma cells (HepG2), and expression of alpha-smooth muscle actin (alpha-SMA) in LX-2 cells. METHODS: LX-2 and HepG2 cells were incubated with various concentrations of Cpd 861 (0.1-0.003 mg/mL) for 1, 2, 3, 5 and 7 d. Cell proliferation was analyzed by 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Effects of Cpd861 on the expression of alpha-SMA mRNA in LX-2 cells were measured by real-time quantitative PCR method using SYBR Green I technology. RESULTS: Cpd 861, at 0.1 mg/mL, significantly inhibited LX-2 cell proliferation (15% decrease relative to control, P<0.05) after 3 d of incubation. The inhibitory effects seemed to increase with the treatment time (25% decrease after 5 d of incubation and 35% decrease after 7 d of incubation, P<0.01). However, Cpd 861 did not affect HepG2 cell proliferation at the same concentration used for LX-2 cells. The expression levels of alpha-SMA mRNA decreased significantly when LX-2 cells were exposed to Cpd 861 for 48 h (59% decrease relative to control, P<0.05) or 72 h (60% decrease relative to control, P<0.01). CONCLUSION: Cpd 861 can significantly inhibit LX-2 cell proliferation in a dose-dependent manner, and reduce the expression levels of alpha-SMA mRNA in LX-2 cells. Since hepatic cell proliferation and high level of alpha-SMA are associated with liver fibrosis, the results suggest that Cpd 861 may be useful in the treatment of this disease.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

Efficacy of gastrostomy feeding in infants and older children receiving chronic peritoneal dialysis.

OBJECTIVE: To assess the efficacy of supplemental gastrostomy tube (g-tube) feeding in infants and children receiving chronic peritoneal dialysis (CPD). DESIGN: Retrospective observational study. SETTING: Pediatric nephrology division of tertiary care center. PATIENTS: Fifteen patients undergoing g-tube insertion while receiving CPD were included in the study, and were subdivided, on the basis of age, into the following groups: infants (< or = 2.5 years, n = 8); older children (> 2.5 years, n = 7). MAIN OUTCOME MEASURES: Assessment of the effect of CPD and g-tube feeding on statural growth assessed by height standard deviation score (SDS) and percentage weight-for-height, and measured anthropometric variables including triceps skinfold thickness (TSF), midarm muscle circumference (MAMC), and midarm mean circumference (MAC). Assessment of the effects of CPD and g-tube feeding on measured biochemical variables including total protein, albumin, cholesterol, triglycerides, and high density lipoprotein. RESULTS: No significant change in height SDS was observed; however, the reported continuing decline in height SDS in infants was arrested. Percentage weight-for-height increased significantly in infants at 6 months (p = 0.008) and 12 months (p = 0.006) following initiation of g-tube feeding. An increase was also observed in the older child group, being significant at 12 months (p = 0.031) following g-tube insertion. Increases in all anthropometric variables occurred in the infant group during CPD and post g-tube insertion, significant only for MAMC at 12 months (p = 0.037) post g-tube insertion. In older children little change occurred during CPD, with all variables increasing post g-tube insertion, significant only for MAMC at 6 months (p = 0.02) and 12 months (p = 0.02). An increase in total protein and albumin was noted; however, no significant changes in any biochemical parameters were observed. CONCLUSIONS: Supplemental g-tube feeding facilitates weight gain in infants and older children receiving CPD and arrests the decline in height SDS traditionally observed in infants with end-stage renal disease. No significant alteration was observed in measured biochemical variables, although an increase in total protein and albumin was noted.

Anthropometry↗
PubMed1999

Oxidation of guanine in cellular DNA by solar UV radiation: biological role.

The formation of cyclobutane pyrimidine dimers (CPD) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) was investigated in Chinese hamster ovary cells upon exposure to either UVC, UVB, UVA or simulated sunlight (SSL). Two cell lines were used, namely AT3-2 and UVL9, the latter being deficient in nucleotide excision repair and consequently UV sensitive. For all types of radiation, including UVA, CPD were found to be the predominant lesions quantitatively. At the biologically relevant doses used, UVC, UVB and SSL irradiation yielded 8-oxodGuo at a rather low level, whereas UVA radiation produced relatively higher amounts. The formation of CPD was 10(2) and 10(5) more effective upon UVC than UVB and UVA exposure. These yields of formation followed DNA absorption, even in the UVA range. The calculated relative spectral effectiveness in the production of the two lesions showed that efficient induction of 8-oxodGuo upon UVA irradiation was shifted toward longer wavelengths, in comparison with those for CPD formation, in agreement with a photosensitization mechanism. In addition, after exposure to SSL, about 19% and 20% of 8-oxodGuo were produced between 290-320 nm and 320-340 nm, respectively, whereas CPD were essentially (90%) induced in the UVB region. However, the ratio of CPD to 8-oxodGuo greatly differed from one source of light to the other: it was over 100 for UVB but only a few units for UVA source. The extent of 8-oxodGuo and CPD was also compared to the lethality for the different types of radiation. The involvement of 8-oxodGuo in cell killing by solar UV radiation was clearly ruled out. In addition, our previously reported mutation spectra demonstrated that the contribution of 8-oxodGuo in the overall solar UV mutagenic process is very minor.

Animals↗
PubMedDate not supplied

Incidence of peritonitis in chronic peritoneal dialysis patients infused with intravenous iron dextran.

BACKGROUND: The Dialysis Outcomes Quality Initiative (DOQI) guidelines, published in 1997, emphasize the need for careful monitoring of iron stores and for provision of adequate iron replacement therapy to achieve target goals of hemoglobin concentration in end-stage renal disease (ESRD) patients, especially those treated with recombinant erythropoietin (rHuEPO). Intravenous iron dextran (IVID) therapy, which has long been used in hemodialysis patients, is increasingly being used in chronic peritoneal dialysis (CPD) patients. In 1997, we began using this form of iron therapy for our CPD patients. However, because considerable data exists to show a relationship between iron metabolism and acute infections, we questioned whether IVID infusion placed our patients at greater risk for peritonitis, the leading cause of death and patient drop-out from CPD therapy. OBJECTIVE: To evaluate the relationship between iron and infection, we studied episodes of peritonitis in CPD patients who were infused with IVID. DESIGN: In a retrospective study of adult CPD patients who received IVID during 1998, we investigated the occurrence of peritonitis episodes and the spectrum of causative organisms. Patients with a hemoglobin level of < 12.5 g/dL who also had a ferritin level < 100 ng/mL or a transferrin saturation level < 20% (or both) and who did not respond to oral iron therapy, were administered between 0.5 g and 1.0 g of IVID in an outpatient hospital setting. We calculated the expected and observed number of peritonitis episodes in these patients within 30, 60, and 90 days after infusion of IVID. RESULTS: During the study period, 56 patients received 77 doses of IVID, with 14 patients requiring 2 or more infusions. Of the 77 doses, 71 were given as a 1-g bolus. The IVID was well tolerated by all patients. Within 90 days of IVID administration, 14 patients developed peritonitis: 6 episodes occurred within 30 days, 7 episodes occurred between 31 and 60 days, and 1 episode occurred between 61 and 90 days after the IVID dosing. The peritonitis rate for patients not receiving IVID was 1 episode per 13.7 patient-months. Taking this rate as the "expected" rate, the expected number of episodes of peritonitis for the study population was 5.6 episodes within 30 days, 11.2 episodes within 60 days, and 16.8 episodes within 90 days following IVID administration. The difference between the expected and observed rates of peritonitis in patients who were dosed with IVID was not statistically different. The spectrum of organisms seen in the peritonitis episodes in the study population was not significantly different from that seen in the peritonitis episodes in our CPD unit population. CONCLUSIONS: There is evidence that IVID infusion therapy can improve anemia and reduce rHuEPO requirements in CPD patients, usually without adverse reaction and without exposing patients to an increased risk of peritonitis. More research is needed in the area of potential increased risk of infection in ESRD patients who are (1) infused with large doses of IVID, and (2) iron-overloaded.

Female↗
PubMed2001

Continuous peritoneal dialysis and the extended care facility.

The projected disproportionate increase in the number of elderly patients reaching end-stage renal disease constitutes a dramatic change in dialysis demographics. The nursing home or extended care facility (ECF) will become an increasingly important feature of care for both rehabilitation and long-term patient management. For continuous peritoneal dialysis (CPD), the ECF has been critically evaluated in only a single specialized, university-based, geriatric facility that included trained peritoneal dialysis nurses providing care. We have trained multiple ECF personnel in 10 community-based ECFs to provide all CPD-related therapy for 93 patients between November 1993 and December 1998, for a total of 289.3 patient-months. All ECFs have maintained their CPD program. Outcome measures, including hospitalization, mortality, technique failure, and peritonitis rates, show the success and feasibility of using community-based ECFs for CPD. The use of multiple ECFs for CPD appears to offer distinct advantages over solo structured ECF programs without jeopardizing outcomes. A highly structured CPD education program for ECF personnel by nephrology staff is manageable and appears critical for the success of maintaining CPD in the ECF.

Aged↗
PubMed1990

[In vitro antibacterial activity of RU 51746 (sodium salt of cefpodoxime). Results of a multicenter study].

Cefpodoxime proxetil, a new oral cephalosporin, is the prodrug ester of cefpodoxime. Minimal inhibitory concentrations (MIC) of RU 51746 (sodium salt of cefpodoxime: CPD) were evaluated by agar dilution for 1 696 bacterial strains isolated in 5 hospitals. For Enterobacteriaceae, MIC 50 and 90% were respectively (micrograms/ml): (1) naturally non bêtalactamase producing species: E. coli, Shigella and Salmonella 0.25-0.5; P. mirabilis 0.06-0.12. (II) chromosomal penicillinase producing species: Klebsiella 0.12-1. (III) chromosomal cephalosporinase producing species: E. cloacae and C. freundii 2-greater than 128; S. marcescens 2-64; indole + Proteus 0.25-64; P. stuartii 0.25-16. Activity of CPD was not modified on plasmid mediated penicillinase producing strains, but CPD was inactive on cephalosporinase hyperproducing strains, and on broad spectrum bêtalactamases producing strains. CPD was inactive on P. aeruginosa (MIC greater than or equal to 64) and on A. baumannii (16-pi 128). Haemophilus, regardless on bêtalactamase production status, were very susceptible to CPD (MIC less than or equal to 0.25) and B. catarrhalis was generally inhibited by 0.12 to 1. CPD was poorly active on methicillin susceptible Staphylococci (MIC 50 and 90%: 2-4) and inactive on methicillin resistant strains. Enterococci and Listeria monocytogenes were generally resistant; Streptococci A, B, C, G and Pneumococci were inhibited by low concentration: 0.002 to 0.25 (MIC 50 and 90%: 0.016-0.032) whereas MIC for other Streptococci were 0.004 to 32 (MIC 50 and 90%: 0.25-4). These antibacterial properties placed CPD in excellent position among oral cephalosporins.

Anti-Bacterial Agents↗