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PubMed2002

Immunohistochemical localization of carboxypeptidases D, E, and Z in pituitary adenomas and normal human pituitary.

Carboxypeptidases may play important role(s) in prohormone processing in normal and neoplastic adenohypophyseal cells of the pituitary. We have recently demonstrated carboxypeptidase E (CPE) and carboxypeptidase Z (CPZ) in the majority of adenohypophyseal cells with carboxypeptidase D (CPD) immunoreactivity largely confined to adrenocorticotrophs. This study evaluated the expression patterns of CPE, CPD, and CPZ immunoreactivity in 48 pituitary adenomas. Our immunohistochemistry demonstrated extensive intracytoplasmic immunoreactivity for CPE, CPD, and CPZ in adrenocorticotrophic hormone (ACTH)-producing adrenocorticotroph cells, prolactin-producing lactotroph cells, and growth hormone (GH)-producing somatotroph cell adenomas, all of which require carboxypeptide processing of prohormones to produce active endocrine hormones. In contrast to the restricted expression in the normal adenohypophysis, CPD appeared to be widespread in the majority of adenomas, suggesting that CPD levels are increased in adenomas. In luteinizing hormone/follicle-stimulating hormone (LH/FSH)-producing gonadotroph adenomas, which do not require carboxypeptidases to produce gonadotropins, only CPZ immunostaining was demonstrated. In null-cell adenomas, CPE immunoreactivity was detected in the majority of tumors, but CPD and CPZ were identified only in a minority of cases. CPE in these cells may process other peptides critical for pituitary cell function, such as chromogranin A or B. These findings suggest that CPs participate in the functioning of pituitary adenomas.

Adenoma↗
PubMed1998

Immunohistochemical localization of carboxypeptidases E and D in the human placenta and umbilical cord.

Carboxypeptidase E (CPE) is highly concentrated in neuroendocrine tissues and is the only carboxypeptidase detected in mature secretory vesicles. Carboxypeptidase D (CPD), a carboxypeptidase with CPE-like activity, is widely distributed in tissues and is present in the trans-Golgi network. Previous work had shown that both CPE and CPD are expressed in the human placenta and that CPD is expressed at much higher levels than CPE. The present work provides evidence for the co-localization of CPE and CPD to basal plate extravillous trophoblasts and maternal uteroplacental vascular endothelial cells, chorionic villous endothelial cells, amnionic epithelial cells, and umbilical venous and arterial smooth muscle cells. Whereas the intensity of CPD immunostaining is similar in the placenta and umbilical cord, CPE staining in the placenta is much weaker than in the umbilical cord, suggesting that CPD plays a more important role in the processing of placental peptides. Immunoelectron microscopy of umbilical venous smooth muscle cells shows subcellular localization of both enzymes to the rough endoplasmic reticulum. In addition, CPE is present just subjacent to the cell membrane. The difference in cellular and subcellular localization between the two enzymes indicates that they perform distinct functions in the processing of placental peptides and proteins.

Carboxypeptidase H↗
PubMed1998

Dynamic contrast perception assessed by pattern masking.

The perceived contrast of a pulsed grating varies markedly with the exposure duration and spatial frequency of the grating. We studied dynamic changes in perceived grating contrast with a pattern-masking paradigm. We measured masking of a brief, localized test pattern (a D6 stimulus, 30 ms in duration) by fixed-contrast cosine grating patterns of varying duration (50-500 ms). The cosine mask pattern had spatial frequency of either 1 or 6 cycles per degree (cpd) at a contrast of 0.3. The D6 test pattern was centered on a light bar of the mask and was either positive peak contrast (same-polarity test and mask) or negative peak contrast (opposite-polarity test and mask). In Experiment 1, the test and mask had simultaneous onset. With a 6-cpd mask, the same-polarity test-threshold elevation versus mask-duration function increases monotonically. For a 1-cpd mask, the same-polarity threshold-mask-duration function is nonmonotonic, with peak masking effect produced by a grating pulse of 80-100 ms. These masking effects are closely congruent with known dynamic contrast effects. With negative tests, masking-duration functions are elevated from same-polarity functions and are essentially similar in shape for 1- and 6-cpd masks. The elevated thresholds suggest inhibitory interaction between ON and OFF pathways, with a similar time course across spatial frequency. In Experiment 2, the D6 test was delayed from mask onset by 33 ms. Positive contrasts only were employed. For 1-cpd stimuli, the delay of test greatly reduced masking at all mask durations and eliminated the nonmonotonic function. This suggests that for low-spatial-frequency patterns, perceived contrast is determined by an early peak component of the neural response. But for 6-cpd stimuli, masking of the delayed test was somewhat greater at all mask durations, consistent with a gradually increasing underlying neural response to the grating. Finally, in Experiment 3, same-polarity masking effects at both spatial frequencies were replicated with negative-contrast test and mask (OFF pathway mediation). This indicates that the ON and OFF pathways have similar response dynamics.

Contrast Sensitivity↗
PubMed2000

Partial complementation of the DNA repair defects in cells from xeroderma pigmentosum groups A, C, D and F but not G by the denV gene from bacteriophage T4.

Endonuclease V (denV) from bacteriophage T4 was examined for its ability to complement the DNA repair defect in xeroderma pigmentosum (XP) cells from complementation groups A, C, D, F and G. The denV gene was introduced into SV40-transformed normal and XP cells using a retroviral vector. Expression of denV resulted in partial correction of UV sensitivity and increased host cell reactivation (HCR) of a UV-damaged reporter gene for XP cells from groups A, C and D, but not those from group G. Expression of denV in XP-F cells resulted in enhanced HCR of a UV-damaged reporter but did not affect UV sensitivity. The observed partial complementation is thought to reflect denV-mediated repair of cyclobutane-pyrimidine dimers (CPD), and is incomplete as denV does not recognize other UV-induced lesions, and may not even efficiently remove all CPD. As XP-F cells are believed to retain near-normal levels of CPD repair in the bulk of the genome, we believe that the disparity in the ability of denV to complement the repair deficiency in these cells results from an increased rate, but not level, of CPD repair. Furthermore, we suggest that the lack of correction in the XP-G cells examined results from an inability to process denV-incised CPD by the base excision repair pathway, as has been suggested for cells from the related genetic disorder, Cockayne syndrome. Expression of denV in repair proficient normal cells also resulted in increased HCR of the UV-damaged reporter construct, possibly arising from an increased rate of CPD repair in these cells.

Bacteriophage T4↗
PubMed2004

Unrepaired cyclobutane pyrimidine dimers do not prevent proliferation of UV-B-irradiated cultured human fibroblasts.

Mutagenic and carcinogenic UV-B radiation is known to damage DNA mostly through the formation of bipyrimidine photoproducts, including cyclobutane dimers (CPD) and (6-4) photoproducts ((6-4) PP). Using high-performance liquid chromatography coupled to tandem mass spectrometry, we investigated the formation and repair of thymine-thymine (TT) and thymine-cytosine (TC) CPD and (6-4) PP in the DNA of cultured human dermal fibroblasts. A major observation was that the rate of repair of the photoproducts did not depend on the identity of the modified pyrimidines. In addition, removal of CPD was found to significantly decrease with increasing applied UV-B dose, whereas (6-4) PP were efficiently repaired within less than 24 h, irrespective of the dose. As a result, a relatively large amount of CPD remained in the genome 48 h after the irradiation. Because the overall applied doses (<500 J m(-2)) were chosen to induce moderate cytotoxicity, fibroblasts could recover their proliferation capacities after transitory cell cycle arrest, as shown by 5-bromo-2'-deoxyuridine (BrdUrd) incorporation and flow cytometry analysis. It could thus be concluded that UV-B-irradiated cultured primary human fibroblasts normally proliferate 48 h after irradiation despite the presence of high levels of CPD in their genome. These observations emphasize the role of CPD in the mutagenic effects of UV-B.

Bromodeoxyuridine↗
PubMed2005

Cooperation between BRCA1 and p53 in repair of cyclobutane pyrimidine dimers.

DNA repair defects can predispose to cancer development and progression. We previously showed that the breast and ovarian cancer susceptibility gene product BRCA1, through p53, upregulates expression of the XPE gene DDB2 encoding the nucleotide excision repair protein p 48. Both XPE and XPC are p53 target genes containing p53 response elements. To further explore the role of BRCA1 and p53 in repair of photoproducts, we eliminated wild type p53 from U2OS osteosarcoma cells and found that cyclobutane pyrimidine dimer (CPD) repair was markedly impaired following UV damage whereas repair of 6-4 photoproduct (6-4 PP) occurred efficiently. Overexpression of p53 in p53-null Calu-6 cells also enhanced CPD repair. In HCC1937 breast cancer cells, harboring mutant BRCA1 and p53 genes, repair of CPD was markedly impaired. Reintroduction of either p53 or BRCA1 using adenovirus vectors into HCC1937 alone had little effect on repair of CPD whereas the combination of p53 and BRCA1 resulted in efficient repair of CPD. Thus there appears to be a cooperative effect between p53 and BRCA1 that may involve induction of repair proteins, inhibition of p53-induced cell death by BRCA1 with altered p53 selectivity towards repair pathways and/or p53-independent effects of BRCA1 on CPD repair.

BRCA1 Protein↗
PubMed1996

Elderly Patients With no Prior Cardiopulmonary Disease Show Ventilation/Perfusion Lung Scan Characteristics That Are Sensitive and Specific for Pulmonary Embolism.

The purpose of the present investigation was to test the hypothesis that stratification according to age, in addition to stratification according to the presence or absence of prior CPD, in elderly patients may show criteria on V/Q lung scans that have a higher sensitivity for acute PE than the entire population, while maintaining a high specificity and high PPV. Data from the PIOPED were evaluated among 1,050 patients with suspected acute PE in whom the diagnosis was made or excluded by pulmonary angiography. Age groups were at or above 70 years of age (n equals 259), 40-69 years of age (n equals 585) and 18-39 years of age (n equals 206). Patients were stratified according to the presence or absence of prior CPD. Lung scans were evaluated on the basis of the cumulative number of mismatched vascular perfusion defects (large or moderate size mismatched segmental perfusion defects). Among patients at or above 70 years of age who had no prior CPD, greater than or equal to 2 matched vascular perfusion defects showed a sensitivity of 23 of 31 (74%), a specificity of 29 of 29 (100%), and a PPV of 23 of 23 (100%). Stratification according to both age and CPD was particularly useful for the evaluation of V/Q lung scans in patients at or above 70 years of age with no prior CPD, although only 23% of patients at or above 70 years of age had no prior CPD.

Journal Article↗
PubMed2002

Analysis of the carboxypeptidase D cytoplasmic domain: Implications in intracellular trafficking.

Metallocarboxypeptidase D (CPD) is a type 1 transmembrane protein that functions in the processing of proteins that transit the secretory pathway. Previously, CPD was found to be enriched in the trans Golgi network (TGN) and to cycle between this compartment and the cell surface. In the present study, the roles of specific regions of the CPD cytosolic tail in intracellular trafficking were investigated in the AtT-20 cell line. When the CPD transmembrane region and cytosolic tail are attached to the C-terminus of albumin, this protein is retained in the TGN and cycles to the cell surface. Deletion analysis indicates that a C-terminal region functions in TGN-retention; removal of 10 amino acids from the C-terminus greatly increases the amount of fusion protein that enters nascent vesicles, which bud from the Golgi, but does not affect the half-life of the fusion protein or the ability of cell surface protein to return to the TGN. Because the 10-residue deletion disrupts a casein kinase 2 (CK2) consensus site, the two Thr in this site (TDT) were mutated to either Ala (ADA) or Glu (EDE). Neither mutation has an increased rate of budding from the TGN, although the ADA mutant has a shorter half-life than either the wild type sequence or the EDE mutant. Adaptor protein-1 and -2 bind to most of the deletion mutants, the EDE point mutant, and the CK2-phosphorylated CPD tail, but not to the wild type tail. Taken together, these results suggest that CPD localization to the TGN requires both static retention involving the C-terminal domain and phosphorylation at a CK2 site, which regulates the binding of adaptor proteins.

Adaptor Protein Complex alpha Subunits↗
PubMedDate not supplied

A population-specific formula predicting creatinine excretion in continuous peritoneal dialysis.

OBJECTIVE: The Cockroft-Gault formula was shown to systematically overestimate the decline in creatinine excretion with age in continuous peritoneal dialysis (CPD) patients and is, therefore, not suitable for studying creatinine excretion. The purpose of the present study was to develop and test a population-specific formula predicting average creatinine excretion in CPD. METHODS: Creatinine excretion in urine plus dialysate was measured in 925 CPD patients. Forty patients were excluded because of evidence of noncompliance. The remaining 885 subjects were randomly grouped into a derivation group (n = 432) and a validation group (n = 453). Stepwise multiple linear regression models were used to predict creatinine excretion in the derivation group. The candidate variables, chosen because they were previously shown to be predictors of creatinine excretion in CPD, included weight (W), age (A), gender (G), diabetes (D), and interaction terms between these four variables. Estimates of creatinine excretion from the best-fit regression formula (CrExcr1) and from the Cockroft-Gault formula (CrExcr2) were compared to creatinine excretion (CrExcr) in the validation group. RESULTS: The best-fit regression model in the derivation group included all four candidate variables (W, A, G, D), but no interaction terms. This model was as follows: CrExcr1 = 302.150 - 4.380A + 171.234G - 39.041D + 11.730W (r2 = 0.477, p < 0.001). In the validation set, CrExcr = -15.795 + 0.988CrExcr1 (r2 = 0.447, p < 0.001), and CrExcr = -303.823 + 0.732CrExcr2 (r2 = 0.340, p < 0.001). When the differences between measured and predicted creatinine excretion did not take into account the sign of each individual difference, CrExcr - CrExcr1 = 201 +/- 156 mg/24 hours, and CrExcr - CrExcr2 = 235 +/- 174 mg/24 hr (p < 0.001) in the validation group. When the sign of the difference was taken into account, CrExcr - CrExcr1 = -28 +/- 149 mg/24 hr, and CrExcr - CrExcr2 = 63 +/- 295 mg/24 hr (p < 0.001). CONCLUSIONS: A population-specific formula predicting creatinine excretion in CPD was derived. This formula has greater accuracy than the Cockroft-Gault formula and can be used in studies of creatinine excretion in CPD.

Adult↗
PubMedDate not supplied

Normal or low initial PTH levels are not a predictor of morbidity/mortality in patients undergoing chronic peritoneal dialysis.

OBJECTIVE: During the past few decades, the pattern of bone disease in uremic patients has changed significantly. There has been an increase in the number of patients with normal or low initial parathyroid hormone (PTH) levels, particularly in patients on chronic peritoneal dialysis (CPD). Previous authors have described a higher prevalence of bone pain, microfractures, and fractures, and higher mortality among these patients. The aim of this study was to determine the incidence, morbidity, and mortality of patients who had a low or normal intact PTH (iPTH) level when they started CPD. DESIGN: We reviewed the records of 251 patients in our program that started CPD during the past 5 years (January 1996-December 2000). Clinical data, laboratory variables, medication, and dialysis parameters/dose were available at every clinic visit (approximately every 4 weeks). Intact PTH was used to express parathyroid function; values 3 times higher than the upper limit of normal (ULN) were assumed to be optimal. Variables predictive of the development of parathyroid dysfunction were calculated by univariate and multivariate logistic regression analysis. RESULTS: Of the patients who started CPD, 15.5% had iPTH values below the ULN (7.6 pmol/L), and an additional 29.5% had an iPTH of less than 3 times the ULN (i.e., between 7.6 and 22.8 pmol/L). We call these two groups of patients the normal/low initial iPTH group. During the follow-up period (3-63 months), we found a trend toward increasing iPTH levels. By the end of the study period, 61.2% of those with normal/low initial iPTH remained in the normal/low iPTH range, and 38.8% had converted to a group with an iPTH range higher than 22.8 pmol/L. The patients who converted their iPTH grouping were younger, fewer of them were diabetics (p = not significant), and they were more frequently on low calcium dialysate (p < 0.05). Hyperphosphatemia was an independent risk factor for subsequent iPTH changes during the course of continuous ambulatory PD treatment. All patients in the normal/low iPTH groups had a low prevalence of bone fractures (3.5%). Also, patients who remained in the normal/low iPTH group at the end of the follow-up period did not have more fractures than those who converted to the hyperparathyroid group (3.8% vs 3.1%). We found no differences in bone fractures between patients with iPTH levels below 22.8 and those with levels above 22.8 pmol/L (3.5% vs 5.4%), nor were there differences in patient and technique survival between these two groups. CONCLUSION: Normal/low initial iPTH is a frequent finding among patients starting CPD. Serum phosphorus was an independent risk factor for subsequent iPTH changes during the course of CPD treatment. Use of low calcium dialysate was significantly higher in patients who converted their iPTH into the high iPTH range. Very few patients with low/normal iPTH had bone-related symptoms (pain and fractures), and their morbidity and mortality did not differ from those patients with a high initial iPTH level.

Blood Urea Nitrogen↗
PubMedDate not supplied

Nutrition indices in obese continuous peritoneal dialysis patients with inadequate and adequate urea clearance.

OBJECTIVE: To test whether better nutrition is associated more with adequate urea clearance than with inadequate urea clearance in obese patients on continuous peritoneal dialysis (CPD). DESIGN: Retrospective analysis of clearance and nutrition indices in obese CPD patients. Only obese patients were analyzed. Obesity was defined as a ratio of actual weight to desired weight (W/DW) > or = 1.2. The dose of dialysis was considered adequate at weekly Kt/V urea > or = 2.0. Small solute clearances and nutrition indices were compared between patients with weekly Kt/V urea < 2.0 and patients with weekly Kt/V urea > or = 2.0 at the first clearance study. SETTING: Four university-affiliated and two private dialysis units in Canada and the United States. PATIENTS: A total of 270 CPD patients with W/DW > or = 1.2 at the first clearance study. RESULTS: Among the 270 obese CPD patients, 157 (58.1%) were underdialyzed (weekly Kt/V urea 1.66 +/- 0.22) and 113 (41.9%) had adequate dialysis (weekly Kt/V urea 2.51 +/- 0.47) at the first clearance study. Creatinine clearance values also differed between the underdialyzed and adequately dialyzed obese groups (55.6 +/- 15.2 vs 87.6 +/- 29.8 L/1.73 m2 weekly, respectively, p < 0.001). The underdialyzed group contained fewer women (39.5% vs 60.2%, p < 0.001) and more patients with anuria (35.0% vs 8.8%, p < 0.001), and had higher serum urea (20.7 +/- 6.9 vs 18.2 +/- 5.3 mmol/L, p = 0.001) and serum creatinine (974 +/- 283 vs 734 +/- 275 micromol/L, p < 0.001), marginally lower serum albumin (35.8 +/- 5.2 vs 37.2 +/- 6.4 g/L, p = 0.082), lower urea nitrogen excretion (5778 +/- 2290 vs 7085 +/- 2238 mg/24 hr, p < 0.001) and indices derived from urea nitrogen excretion (protein nitrogen appearance and normalized protein nitrogen appearance), and lower creatinine excretion (1034 +/- 349 vs 1217 +/- 432 mg/24 hr, p < 0.001) and indices derived from creatinine excretion (lean body mass normalized to actual or desired weight) than the adequately dialyzed group. CONCLUSION: Nutrition indices derived from urea nitrogen and creatinine excretion are worse in underdialyzed than in adequately dialyzed obese CPD patients. This finding may have clinical importance, despite the mathematical coupling between small solute clearances and excretion rates in cross-sectional studies, because of evidence from other studies that small solute excretion rate in cross-sectional studies is a robust Independent predictor of outcome in CPD.

Adult↗
PubMedDate not supplied

A novel objective nutritional score for children on chronic peritoneal dialysis.

OBJECTIVES: To establish a novel nutritional score based on a series of objective parameters capable of detecting protein-calorie malnutrition in children being treated with chronic peritoneal dialysis (CPD), to test the score in a healthy pediatric population, and to apply it to children on CPD to evaluate their nutritional status. STUDY POPULATION: 264 healthy school children (mean age 8.69 +/- 3.26 years, range 3.05-14.98 years) and 29 patients treated with CPD for 1.75 +/- 1.02 years (mean age 10.54 +/- 6.28 years, range 2.8-15.24 years). METHODS: Nutritional status was evaluated by means of three sets of measurements: anthropometric (A1 and A2) and bioimpedance analysis (BIA) measurements. Anthropometry included two sets of measures: set A1 consisted of height (H), weight (W), and body mass index (BMI); set A2 consisted of midarm muscle circumference (MAMC), arm muscle area (AMA), and arm fat area (AFA). The BIA measurements included reactance, phase angle, and distance. All parameters are expressed as standard deviation scores (SDS).Tanner's, Rolland-Cachera's, and Frisancho's data were used as references for H, W, BMI, MAMC, AMA, and AFA; personal data obtained from 551 healthy boys and girls were used for the BIA indices. The nine anthropometry and BIA parameters were given scores of 1 to 5: 5 = > 0 SDS, 4 = < or = 0 and > -1 SDS, 3 = < or = -1 and > -2 SDS, 2 = <-2 and > -3 SDS, and 1 = < or = -3 SDS. Average scores were established for each of A1, A2, and BIA, and then summed to obtain the anthropometry-BIA nutrition (ABN) score. To establish the cutoff value between normal nutritional status and malnutrition, the method was first applied to the 264 healthy children; distribution percentiles were calculated for each area score and the ABN score. The ABN score corresponding to the 3rd percentile was considered the limit of normality and then applied three times to the 29 children on CPD, for a total of 87 nutritional assessments. RESULTS: The score corresponding to the 3rd percentile in the population of healthy children was 10.33. Among the CPD-treated children, 41.4% of the ABN scores were higher than 10.33 (indicating a state of normal nutrition) and 58.6% were lower (indicating various degrees of malnutrition). Severe malnutrition was found in only 1.1% of the cases. The values of all nine A1, A2, and BIA parameters, as well as serum albumin levels, were significantly higher in patients with an ABN score > 10.33 than in those with a score < 10.33. CONCLUSION: The ABN score is a simple and objective method of assessing, in clinical practice, the nutritional status of children on CPD.

Adolescent↗
PubMedDate not supplied

Cytostatic effects of various alkyl phospholipid analogues on different cells in vitro.

Phospholipid analogues were studied with regard to their cytostatic activity on different tumour cell lines and on murine bone marrow cells. Compounds compared for their activity were alkylglycero- and alkyl-phosphocholines with the corresponding serines and the alkylphosphocholines and -serines with the corresponding phosphono derivatives. Moreover, compounds containing cytidine 5'-diphosphate instead of the phospho (or phosphono-) choline or serine moiety were studied. rac-2-Chloro-2-deoxy-2-deoxy-1-0-hexadecyl-glycero-3-phosphocholine (cpd. Id), hexadecylphosphocholine (cpd. Ia) as well as hexadecylphosphonocholine (cpd. Ib) inhibited growth of tumour cells in suspension and monolayer culture and their colony and cluster formation in agar culture but not that of bone marrow cells. The exchange of choline for serine in these compounds results in the loss of this type of antitumour specificity. However, dodecylphospho-L-serine (cpd. IIc) is as specific as the choline derivatives Ia, b, d mentioned. Thus, for serine compounds the specificity for tumour cells might depend in a critical way on the length of the alkyl chain. The phosphono compounds Ib, IIb show almost the same activity as the corresponding compounds hexadecylphosphocholine (cpd. Ia) or hexadecylphosphoserine (cpd. IIa). The CDP-derivatives (IIIa, d, e, f) inhibited growth of tumour cells in suspension or monolayer cultures but not the colony and cluster formation in agar (i.e. they do not decrease the plating efficiency) from either tumour or bone marrow cells.

Alkylation↗
PubMed1992

Five years' experience of the Italian Registry of Pediatric Chronic Peritoneal Dialysis.

The results of the first 5 years' experience of the Italian Registry of Pediatric Chronic Peritoneal Dialysis (CPD) (1986-1990) are presented. Patients of less than 15 years of age at start of dialysis were enrolled and clinical data collected until the age of 19. The number of the dialysis centres participating in the Registry increased from 7 in 1986 to 15 in 1990. The total number of patients on CPD was 119, the number of new patients per year ranged from 15 to 28 and the percentage of all dialysed children treated with CPD increased from 40% in 1986 to 49% in 1990. The age of patients at start of CPD was 8.5 +/- 4.9 years and 16% of them were under 2 years. Only CAPD was utilized in 1986, while CCPD/NPD accounted for 53% and 65% of the treated patients in 1989 and 1990, respectively. At 4 years, patient survival was 91.3% and technique survival 79.3%. A comparison between data of 48 patients on CPD and 34 on hemodialysis, who started dialysis in the period 1989-1990, showed that CPD was the most frequent form of initial therapy (56%) and was the treatment of choice for children younger than 4 years.

Age Factors↗
PubMed2005

Continuing professional development--supporting the delivery of quality healthcare.

Patients and the general public have a right to expect that doctors remain up to date and are professionally competent. The ultimate aim of continuing professional development (CPD) is to contribute to high-quality patient care. The General Medical Council in the UK has published guidance in relation to standards for CPD, appraisal and revalidation. Doctors in the UK participate in an annual appraisal, the outcome of which is the development of the Personal Development Plan. This paper describes a framework for effective CPD and includes methods of self-assessment of clinical practice. Contributions to effective CPD come from 3 sources--doctors, CPD providers and accrediting bodies. The CPD system of recording credits currently in use by the Royal Colleges of Physicians in the UK is also described.

Education, Medical, Continuing↗
PubMed2005

Outcome of patients on chronic peritoneal dialysis undergoing peritoneal catheter removal because of peritonitis.

Peritoneal catheter removal may be clinically indicated in the management of peritonitis. The data on the course of patients undergoing peritoneal catheter reinsertion after removal for peritonitis are limited. The present study was designed to examine what happens to patients on chronic peritoneal dialysis (CPD) after peritoneal catheter removal for peritonitis. We retrospectively reviewed the charts of patients who developed peritonitis between January 1, 1990, and September 1, 2002. We identified 1146 episodes of peritonitis; in 189 of the episodes (16%), the peritoneal catheter was removed. Catheters were reinserted in 88 of those patients (47%). Reasons for peritoneal catheter removal among the 88 patients who underwent peritoneal catheter reinsertion included unit protocol (51%), poor response to antibiotics (46%), and exit-site or tunnel infection (3%). Reasons for peritoneal catheter removal among the 101 patients in whom the peritoneal catheter was not reinserted included unit protocol (62%), poor response to antibiotics (20%), and extensive history of peritonitis (18%). After reinsertion, the new peritoneal catheter remained in place for a mean of 15.4 +/- 15.4 months (range: 1-75 months). In 37 of the 88 patients with reinserted peritoneal catheters (42%), the catheters remained in place for longer than 1 year. The remaining 6 patients underwent transplantation or were transferred to another facility. Of the remaining 51 patients whose new peritoneal catheters lastedfor less than I year, 13 (25.5%) died, and 32 (63%) were transferred permanently to hemodialysis. Of the 101 patients who did not have a peritoneal catheter reinserted, 23 (23%) died within the 2-week period following the onset of peritonitis. The rest were transferred to hemodialysis. The reasons noted for not reinserting the peritoneal catheter included frequent episodes of peritonitis, patient unwillingness to retry CPD therapy, psychosocial reasons, bowel perforation, or transfer to an institution unable to perform CPD therapy. We conclude that, among patients who medically require peritoneal catheter removal because of peritonitis, few will successfully return to long-term CPD therapy. Of the patients who required peritoneal catheter removal in our study, 23% died within the first 2 weeks after the onset of peritonitis, before catheter reinsertion could be considered. Only 47% of the patients underwent a successful catheter reinsertion; and, of those, only 34% remained on CPD therapy I year later Thus, only 20% of patients undergoing PD catheter removal remain on CPD therapy 1 year after catheter removal.

Anti-Bacterial Agents↗
PubMed1990

Growth of small children managed with chronic peritoneal dialysis and nasogastric tube feedings: 203-month experience in 14 patients.

This 203-month experience with CPD and NG feedings in 14 small children weighing less than or equal to 10 kg at initiation of CPD for ESRD, provides evidence that CPD and vigorous nutritional therapy is effective in maintaining and improving growth until a successful renal transplant can be performed. Nutritional therapy should be initiated early, if possible when growth begins to decline even before the onset of ESRD and the need for CPD. Infants who are less than or equal to 4 months old at initiation of CPD are more likely to have a complicated clinical course and poor growth, despite the provision of CPD and vigorous nutritional support. More experience with this group of patients is needed to determine appropriate therapy.

Child, Preschool↗
PubMed1984

Antigenic relationships among sheep pox, goat pox and contagious pustular dermatitis viruses.

Antigenic relationships among sheep pox, goat pox and contagious pustular dermatitis (CPD) viruses were determined by serological techniques using soluble antigens partially purified by DEAE-cellulose chromatography. Homologous antigen-antibody reactions were characterized by the presence of 7 precipitation lines with sheep pox and of 5 ones each with goat pox and CPD viruses. The nature of cross-reactions of sheep pox, goat pox and CPD virus soluble antigens with corresponding sera suggested that sheep pox virus shared 3 soluble antigenic components with goat pox and either 3 or 4 ones with CPD virus. Goat pox virus shared either 2 or 3 soluble antigenic components with CPD virus. Cross-neutralization tests revealed an one-way cross of goat pox virus with sheep pox and CPD viruses, respectively. The results showed that the 3 viruses in question share common soluble antigenic components.

Antigens, Viral↗