Antibody-Mediated Rejection in Sensitized Nonhuman Primates: Modeling Human Biology.

We have established a model of sensitization in nonhuman primates and tested two immunosuppressive regimens. Animals underwent fully mismatched skin transplantation, and donor-specific antibody (DSA) response was monitored by flow cross-match. Sensitized animals subsequently underwent kidney transplantation from their skin donor. Immunosuppression included tacrolimus, mycophenolate, and methylprednisolone. Three animals received basiliximab induction; compared with nonsensitized animals, they showed a shorter mean survival time (4.7 ± 3.1 vs. 187 ± 88 days). Six animals were treated with T cell depletion (anti-CD4/CD8 mAbs), which prolonged survival (mean survival time 21.6 ± 19.0 days). All presensitized animals showed antibody-mediated rejection (AMR). In two of three basiliximab-injected animals, cellular rejection (ACR) was prominent. After T cell depletion, three of six monkeys experienced early acute rejection within 8 days with histological evidence of thrombotic microangiopathy and AMR. The remaining three monkeys survived 27-44 days, with mixed AMR and ACR. Most T cell-depleted animals experienced a rebound of DSA that correlated with deteriorating kidney function. We also found an increase in proliferating memory B cells (CD20(+) CD27(+) IgD(-) Ki67(+) ), lymph node follicular helper T cells (ICOS(+) PD-1(hi) CXCR5(+) CD4(+) ), and germinal center (GC) response. Depletion controlled cell-mediated rejection in sensitized nonhuman primates better than basiliximab, yet grafts were rejected with concomitant DSA rise. This model provides an opportunity to test novel desensitization strategies.

Neutralizing BAFF/APRIL with atacicept prevents early DSA formation and AMR development in T cell depletion induced nonhuman primate AMR model.

Depletional strategies directed toward achieving tolerance induction in organ transplantation have been associated with an increased incidence and risk of antibody-mediated rejection (AMR) and graft injury. Our clinical data suggest correlation of increased serum B cell activating factor/survival factor (BAFF) with increased risk of antibody-mediated rejection in alemtuzumab treated patients. In the present study, we tested the ability of BAFF blockade (TACI-Ig) in a nonhuman primate AMR model to prevent alloantibody production and prolong allograft survival. Three animals received the AMR inducing regimen (CD3-IT/alefacept/tacrolimus) with TACI-Ig (atacicept), compared to five control animals treated with the AMR inducing regimen only. TACI-Ig treatment lead to decreased levels of DSA in treated animals at 2 and 4 weeks posttransplantation (p < 0.05). In addition, peripheral B cell numbers were significantly lower at 6 weeks posttransplantation. However, it provided only a marginal increase in graft survival (59 ± 22 vs. 102 ± 47 days; p = 0.11). Histological analysis revealed a substantial reduction in findings typically associated with humoral rejection with atacicept treatment. More T cell rejection findings were observed with increased graft T cell infiltration in atacicept treatment, likely secondary to the graft prolongation. We show that BAFF/APRIL blockade using concomitant TACI-Ig treatment reduced the humoral portion of rejection in our depletion-induced preclinical AMR model.

COL1A1 gene -1997G/T polymorphism and risk of osteoporosis in postmenopausal women: a meta-analysis.

Studies investigating the association between the COL1A1 gene -1997G/T polymorphism and the risk of osteoporosis in postmenopausal women have reported conflicting results. We performed a meta-analysis based on the evidence currently available from the literature to make a more precise estimation of this relationship. We conducted searches of the published literature in the PubMed and Embase databases up to September 2014. We estimated the pooled odds ratios with their 95% confidence intervals to assess the associations using fixed- or random-effect models. Publication bias was investigated by Begg's funnel plot. Meta-analysis was performed using the STATA package version 12.0. No significant association was found between the -1997G/T polymorphism in the COL1A1 gene and osteoporosis risk in the total population analysis (TT vs GG: OR = 1.28, 95%CI = 0.76-2.17; TT vs GT: OR = 1.04, 95%CI = 0.60-1.78; dominant model: OR = 0.84, 95%CI = 0.50-1.40; recessive model: OR = 1.18, 95%CI = 0.84- 1.66). In a subgroup analysis by nationality, the results also showed that no significant associations between the COL1A1 gene -1997G/T polymorphism and osteoporosis risk existed in either Caucasian or Asian populations. No evidence of publication bias was found. In conclusion, the COL1A1 gene -1997G/T polymorphism might not be a risk factor for osteoporosis in postmenopausal women. Further large and well-designed studies are needed to confirm these conclusions.

Costimulation blockade alters germinal center responses and prevents antibody-mediated rejection.

De novo donor-specific antibody (DSA) after organ transplantation promotes antibody-mediated rejection (AMR) and causes late graft loss. Previously, we demonstrated that depletion using anti-CD3 immunotoxin combined with tacrolimus and alefacept (AMR regimen) reliably induced early DSA production with AMR in a nonhuman primate kidney transplant model. Five animals were assigned as positive AMR controls, four received additional belatacept and four received additional anti-CD40 mAb (2C10R4). Notably, production of early de novo DSA was completely attenuated with additional belatacept or 2C10R4 treatment. In accordance with this, while positive controls experienced a decrease in peripheral IgM(+) B cells, bela- and 2C10R4-added groups maintained a predominant population of IgM(+) B cells, potentially indicating decreased isotype switching. Central memory T cells (CD4(+) CD28(+) CD95(+)) as well as PD-1(hi) CD4(+) T cells were decreased in both bela-added and 2C10R4-added groups. In analyzing germinal center (GC) reactions in situ, lymph nodes further revealed a reduction of B cell clonal expansion, GC-follicular helper T (Tfh) cells, and IL-21 production inside GCs with additional belatacept or 2C10R4 treatment. Here we provide evidence that belatacept and 2C10R4 selectively suppresses the humoral response via regulating Tfh cells and prevents AMR in this nonhuman primate model.

The significant role of ATG5 in the maintenance of normal functions of Mc3T3-E1 osteoblast.

OBJECTIVE: To observe the effects of autophagy-related gene 5 (ATG5) on the proliferation, differentiation, and apoptosis of Mc3T3-E1 osteoblast as well as the effects of ATG5 on apoptosis of osteoblasts under the conditions of non-oxidative stress and oxidative stress. MATERIALS AND METHODS: ATG5 overexpressing and silencing cell lines were established in this experiment with lentiviral vector and transcription activator-like effect or nuclease (Talen) technique, respectively, using Mc3T3-E1 cells. Cell counting kit-8 (CCK-8) was used to detect the proliferation rate of osteoblasts, and flow cytometry was applied to detect the impacts of overexpressed and silenced ATG5 on the cell cycle. Alizarin red staining was used to detect the mineralization capacity of osteoblasts after 4-week osteoinduction differentiation. Quantitative Real-time polymerase chain reaction (qRT-PCR) and Western blot methods were adopted to detect the levels of gene and protein expressions of runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and collagen I (COL-I) correlated with osteoblast differentiation after 48 h of osteoinduction differentiation. The staining with Annexin V-phycoerythrin/7-amino-actinomycin D (Annexin V-PE/7AAD) and flow cytometry were performed to detect the influence of ATG5 on osteoblast apoptosis. RESULTS: Stable ATG5 overexpressing and silencing Mc3T3-E1 cell lines were established successfully. CCK-8 test results showed that ATG5 silence inhibited cell proliferation, but the overexpression of ATG5 did not result in an obvious change in cell proliferation. Cell cycle did not change when ATG5 was overexpressed, while was stagnated in S-phase when silenced. The number of mineralized nodules of cells was reduced notably when ATG5 was silenced, while the overexpression of ATG5 did not have an impact on mineralization capacity of the cell after 4-week of osteoinduction differentiation. The test results of qRT-PCR and Western blotting suggested that ATG5 silence inhibited the gene and protein expressions of Runx2, OCN, and COL-I, while the influence of overexpressed ATG5 on the expressions of genes related to osteoblastic differentiation was not obvious after 48 h of osteoinduction differentiation. ATG5 silence made the cells easier to be damaged by hydrogen peroxide, which resulted in the rise of apoptosis rate of osteoblasts, while the overexpressed ATG5 inhibited osteoblast apoptosis after treatment with hydrogen peroxide for 12 h. CONCLUSIONS: ATG5 silence can lead to inhibition of osteoblast proliferation and differentiation. Moreover, it makes the cells easier to be damaged by oxidative stress, and it causes an increase in apoptosis. However, the overexpression of ATG5 strengthens the anti-oxidative capacity of osteoblasts and reduces apoptosis. ATG5 may be an effective target of anti-oxidative therapy for osteoporosis, which brings a new direction for the treatment of osteoporosis.

Early treatment of SIV+ macaques with an α4ß7 mAb alters virus distribution and preserves CD4+ T cells in later stages of infection.

Integrin α4ß7 mediates the trafficking of leukocytes, including CD4+ T cells, to lymphoid tissues in the gut. Virus mediated damage to the gut is implicated in HIV and SIV mediated chronic immune activation and leads to irreversible damage to the immune system. We employed an immuno-PET/CT imaging technique to evaluate the impact of an anti-integrin α4ß7 mAb alone or in combination with ART, on the distribution of both SIV infected cells and CD4+ cells in rhesus macaques infected with SIV. We determined that α4ß7 mAb reduced viral antigen in an array of tissues of the lung, spleen, axillary, and inguinal lymph nodes. These sites are not directly linked to α4ß7 mediated homing; however, the most pronounced reduction in viral load was observed in the colon. Despite this reduction, α4ß7 mAb treatment did not prevent an apparent depletion of CD4+ T cells in gut in the acute phase of infection that is characteristic of HIV/SIV infection. However, α4ß7 mAb appeared to facilitate the preservation or restoration of CD4+ T cells in gut tissues at later stages of infection. Since damage to the gut is believed to play a central role in HIV pathogenesis, these results support further evaluation of α4ß7 antagonists in the study and treatment of HIV disease.

Decision-related factors and attitudes toward donation in living related liver transplantation: ten-year experience.

INTRODUCTION: Living related liver transplantation (LRLT) has been performed since 1994 in Korea; more than 600 donors have contributed to our successful LRLT program for 10 years. Although the decision to donate is difficult and the donors need a formal psychosocial assessment, no system has been available to us for the assessment. This survey was performed as a presurveillance for the development of a psychosocial assessment protocol. METHODS: A survey questionnaire included 31 questions on general and medical characteristics, factors, and processes related to the decision for donation. Donors of partial livers at least 6 months ago during the period from December 1994 to August 2003 and whose address could be confirmed by telephone were enrolled in the study. RESULTS: A questionnaire was sent by mail to 441 contactable donors of whom 209 (47.4%) responded. Male-to-female ratio was 2:1 and mean age was 32.8 years (range: 16 to 60 years). The number of spousal donors was 120 (57.4%) and 164 (78.5%) donors were employed at the time of donation. Protestants, Buddhists, and Catholics were 29.2%, 19.1%, and 14.8%, respectively. Parents were the most common recipients (33.0%), followed by siblings (17.2%), extended family members (17.2%), and children (15.8%); one hundred eighty nine (90.4%) donors had decided by themselves, the major reason for donation in 192 (91.9%) donors was "to save the lives of family members and relatives." The first person who suggested donation was the donor (64.1%), followed by family members (23.9%) or the attending physicians (8.6%). Although 70.8% of donors answered that they were not hesitant to donate at the time of decision, 44.5% were uneasy at the possibility of being unable to sustain a normal life after donation, at their lack of knowledge on organ donation, and about the pain and fear of surgery. Family members and relatives (53.3%), medical personnel (46.7%), and previous donors (35.4%) were the preferable counselors compared to transplantation institutions and clergymen. The large majority (80.8%) of donors would encourage others to donate. CONCLUSIONS: Although the decision to donate was made by the donors themselves in most cases and they appeared firm and determined about their decision, a significant number of donors felt uneasy about possible complications of organ donation and effects on their lives after donation. A precise and formal psychosocial assessment protocol is needed to support and secure their decision before and after donation.

Inhibition of cytokine-induced vascular cell adhesion molecule-1 expression; possible mechanism for anti-atherogenic effect of Agastache rugosa.

Adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) play an important role during the early stages of atherogenesis. Agastache rugosa has an anti-atherogenic effect in low density lipoprotein receptor -/- mice. Moreover, A. rugosa reduced macrophage infiltration and VCAM-1 expression has been localized in aortic endothelium that overlies early foam cell lesions. This study ascertained that tilianin (100 microM), a major component of A. rugosa, inhibits the tumor necrotic factor-alpha (TNF-alpha)-induced expression of VCAM-1 by 74% in cultured human umbilical vein endothelial cells (HUVECs). Also, tilianin (100 microM) reduced TNF-alpha-induced activation of nuclear factor-kappaB in HUVECs.

Benzodiazepine discontinuation difficulties in panic disorder: conceptual model and outcome for cognitive-behavior therapy.

There is consistent support for the efficacy of cognitive-behavior therapy (CBT) to aid the successful discontinuation of benzodiazepine (BZ) medication in patients with panic disorder, and help these individuals maintain treatment gains while off medication. In this article, we provide a conceptual model for BZ discontinuation difficulties in patients with panic disorder. Outcome studies are reviewed, and are placed in the context of other evidence for the efficacy of CBT in patients with this disorder.

Dietary hematein ameliorates fatty streak lesions in the rabbit by the possible mechanism of reducing VCAM-1 and MCP-1 expression.

Hematein is a compound isolated from Caesalpinia sappan that has been used in oriental medicine as both an analgesic and an anti-inflammatory agent. In this study, we examined the anti-atherogenic potential of hematein using cholesterol-fed New Zealand White (NZW) rabbits. NZW rabbits were divided into a hematein-supplemented (0.05% in diet) group (n=6), a probucol-supplemented (0.25% in diet) group (n=6), and a control group (n=6). After 8 weeks of treatments, the extent of the atherosclerotic lesions was significantly reduced in the hematein-supplemented group and the probucol-supplemented group without changing plasma lipoprotein levels. Hematein and probucol prevented the up-regulation of the vascular cell adhesion molecule-1 (VCAM-1) expression on the descending aorta induced by cholesterol diet. In culture, hematein also significantly inhibited the secretion of soluble VCAM-1 and of monocyte chemotactic protein-1 (MCP-1) respectively induced by tumor necrotic factor alpha (TNF-alpha) and mildly oxidized low density lipoprotein in human umbilical vein endothelial cell (HUVEC) culture. Also, hematein inhibited monocyte adhesion to endothelial cell and the activation of NF-kappaB in HUVECs stimulated with TNF-alpha. The results of the present study suggest that the anti-atherogenic effect of hematein is not related to control of the plasma lipid profile but probably related to the inhibition of VCAM-1 and MCP-1 expression resulting in an amelioration of lesion development in the rabbit.

Relative reactivity of DTPA, immunoreactive antibody-DTPA conjugates, and nonimmunoreactive antibody-DTPA conjugates toward indium-111.

Anti-human serum albumin antibody (Ab) was reacted with cyclic DTPA dianhydride (cDTPAA) at various cDTPAA/Ab molar ratios between 1 and 40. Using a carrier In titration method for DTPA and DTPA-antibody conjugate (Ab-DTPA), we determined that the above reactions produced between 0.1 and 11 DTPA molecules per either immunoreactive antibody (sAb) or nonimmunoreactive antibody (nAb). The percentage of sAb remaining after the above reactions was between 88 and 62%. The reaction of no-carrier-added 111In with the reaction mixture from cDTPAA/Ab molar ratios of 1 to 40 gave radiochemical yields less than or equal to 25% for the respective Ab-DTPA. The rest of the 111In activity was associated with free DTPA. Our results indicate that Ab-DTPA containing greater than 1 DTPA molecule per Ab is more reactive than that containing less than 1 DTPA but is about as reactive as free DTPA. This allows us to label in the presence of free DTPA and consequently prevent colloid formation. The percentage of 111In activity incorporated into sAb-DTPA from the reactions at these molar ratios was similar to that found from the uv analysis. This indicates that the reactivity of sAb-DTPA and nAB-DTPA from the same conjugation reaction is similar. As a result, we were able to conjugate about one DTPA molecule to the Ab without causing deactivation of the Ab and label it with 111In in the presence of excess DTPA. We obtained a specific activity of 6 muCi 111In per microgram of Ab using research grade 111In without further purification.

Molecular characterization of segments 7-10 of Dendrolimus punctatus cytoplasmic polyhedrosis virus provides the complete genome.

The nucleotide sequences of genomic segments S7-S10 from Dendrolimus punctatus cypovirus strain Hunan (DpCPV-Hn) have been determined. This provides the complete genome sequences of DpCPV-Hn. Each segment of S7-S10 possess a single segment each. Homology searches showed that the nucleotide sequences and the deduced amino acid sequences of DpCPV S7-10 had high level of identities with those of Bombyx mori cypovirus (BmCPV) S7-10, respectively. While the amino acid sequences of the proteins encoded by DpCPV S7 and S8 have low identities with those of the proteins encoded by type 14 Lymantria dispar cypovirus S7 and S8, respectively. DpCPV S7 encodes viral structural protein VP5, S8 and S9 encode viral non-structural proteins, and S10 encodes polyhedrin gene, according to the function of the genome segments of BmCPV. There are glutamic-acid-rich and proline-rich domains in the central region of DpCPV S8 encoded protein. A nuclear localization signal was found in the protein encoded by DpCPV S9. Phylogenetic analysis of RNA-dependent RNA polymerases from nine viruses of the family Reoviridae and polyhedrin from eight viruses of the genus Cypovirus indicate that DpCPV is a type 1 cypovirus, more closely related to BmCPV than to other cypovirus species. These results also support the classification of CPV groups based on the electrophoretic migration of genomic dsRNA.

Review article: current therapeutic options for radiation proctopathy.

Radiation proctopathy is a common unfortunate complication following radiation therapy of pelvic malignancies. Symptoms of chronic radiation proctopathy include haematochezia, urgency, constipation, tenesmus, diarrhoea and rectal pain. Currently, a wide variety of pharmacological options, endoscopic cautery techniques and surgical procedures have been proposed for the treatment of chronic radiation proctopathy. Although these have been proposed primarily as treatment for rectal bleeding, the control of other symptoms has been noted with some of these agents. Pharmacological options include 5-aminosalicylic acid preparations, coticosteroid enemas, sucralfate (oral, enemas), formalin, short chain fatty acid enemas, oestrogen/progesterone, hyperbaric oxygen, antioxidants, sodium pentosan polysulphate and misoprostol rectal suppositories. Of these, sucralfate and formalin therapy appear to be effective for bleeding control. Misoprostol rectal suppositories and oral sucralfate may be useful in the prevention of acute and chronic symptoms of radiation proctopathy. Endoscopic cautery techniques have included the use of Nd:YAG laser and argon laser for coagulation of bleeding neovascular telangiectasias. Argon plasma coagulation offers a safe non-contact method of delivering haemostasis which has proven to be particularly useful in targeting difficult to reach lesions tangentially. Surgery is generally reserved for severe refractory cases involving ongoing haemorrhage, obstruction, stricture formation, fistulas and perforation. Given that formal randomized placebo-controlled studies are lacking for most treatments, the management of these patients is often challenging and unclear. Hence, there is a need for more research and education on radiation proctopathy.

Portal vein gas, a changing clinical entity. Report of 7 patients and review of the literature.

OBJECTIVE: To assess the clinical significance of portal vein gas (PVG) demonstrated by computed tomography (CT). DESIGN: Review of medical records. SETTING: Three network-affiliated hospitals providing both primary community-based and tertiary services. METHODS: Review of diagnosis, clinical circumstances, and significance of PVG in 7 patients detected by CT during a 3-year period in 3 affiliated hospitals. RESULTS: Four of 7 patients underwent laparotomy; 1 patient refused surgery. Two patients were treated with intravenous antibiotics only and had uneventful clinical courses. Of the 3 patients who died, 1 refused and 2 underwent laparotomy. CONCLUSIONS: This series indicates that more sensitive imaging and more widespread use of endoscopic retrograde cholangiopancreatography, colonoscopy, and liver transplantation have changed the clinical presentation of PVG; PVG may be found in various clinical settings that do not mandate laparotomy; and the significance of PVG must be derived from the clinical context of the individual patient.

Ketanserin attenuates the behavioural effects of corticosterone: implications for 5-HT(2A) receptor regulation.

The effects of chronic corticosterone treatment on sexual behaviour and wet-dog shakes were investigated in both female and male rats. The serotonergic type 2A (5-HT(2A)) receptor antagonist ketanserin was administered to test the hypothesis that the behavioural effects of corticosterone were mediated by increased 5-HT(2A) receptor activity. Rats were randomly assigned to one of four chronic treatment groups: control, ketanserin alone, corticosterone alone, or ketanserin and corticosterone. Ketanserin attenuated the corticosterone-induced changes in both sexual behaviour and wet-dog shakes. Ketanserin alone had no effect on these behaviours. Results suggest that increased 5-HT(2A) receptor activity mediates the effects of corticosterone on sexual behaviour and wet-dog shakes.

Corticosterone regulation of 5-HT2A receptor-mediated behaviors: attenuation by melatonin.

The effects of chronic corticosterone treatment on sexual behavior and on wet-dog shakes (WDS), a serotonergic type 2A (5-HT2A) receptor-mediated behavior, were explored in the male rat. In addition, the effects of acute melatonin treatment, both alone and in combination with corticosterone, were investigated. Chronic injections of corticosterone resulted in an overall decrease in consummatory measures of sexual behavior, and an increase in WDS. Furthermore, although an acute injection of melatonin alone had no effect on any recorded behavior, it attenuated the effects of corticosterone on sexual behavior and WDS. The data suggest that in the context of 5-HT2A receptor-mediated behaviors, melatonin has possible implications as a 5-HT2A antagonist.

Cognitive-behavior therapy for discontinuation of SSRI treatment of panic disorder: a case series.

In this report we describe the outcome of eight outpatients with panic disorder and agoraphobia who discontinued their treatment with a selective serotonin reuptake inhibitor (SSRI) in the context of a structured, group program of cognitive-behavior therapy. All patients successfully discontinued their SSRI medication while demonstrating clinical improvement. These results were maintained at 3-month follow-up. This case series suggests that manualized CBT for discontinuation of benzodiazepine treatment for panic disorder may be successfully applied to SSRI discontinuation as well.

High dose rate vaginal brachytherapy in early stage endometrial carcinoma: preliminary analysis.

From 1987 to 1993, 69 women diagnosed with FIGO stages I and II carcinoma of the endometrium underwent postoperative adjuvant irradiation (RT) under protocol with high dose rate (HDR) afterloading vaginal apex brachytherapy. All patients initially underwent total abdominal hysterectomy and bilateral salpingo-oopherectomy. Forty-four women received HDR brachytherapy alone and 25 received external beam RT as well as HDR brachytherapy. The median follow-up was 45 months. The 5-year disease-free survival was 92% and the overall survival rate was 79%. Multivariate Cox regression analysis revealed that grade, age, and stage were significant predictors of survival. The overall acute and late side effects were minimal. It appears that HDR vaginal brachytherapy is prevention of vaginal recurrence in endometrial carcinoma and should be considered an effective treatment option.

Evaluating blunt abdominal trauma with sonography: a cost analysis.

Ultrasonography (US) is becoming increasingly utilized in the United States for the evaluation of blunt abdominal trauma (BAT). The objective of this study was to assess the cost impact of utilizing US in the evaluation of patients with BAT in a major trauma center. All patients sustaining BAT during a 6-month period before US was used at our institution (Jan-Jun 1993) were compared to BAT patients from a recent period in which US has been utilized (Jan-Jun 1995). The numbers of US, computed tomography (CT), and diagnostic peritoneal lavage (DPL) were tabulated for each group. Financial cost for each of these procedures as determined by our finance department were as follows: US $96, CT $494, DPL $137. These numbers are representative of actual hospital expenditures exclusive of physician fees as calculated in 1994 U.S. dollars. Cost analysis was performed with t test and chi squared test, and significance was defined as P < 0.05. There were 890 BAT admissions in the 1993 study period and 1033 admissions in the 1995 study period. During the 1993 period, 642 procedures were performed on the 890 patients to evaluate the abdomen: 0 US, 466 CT, and 176 DPL (see table) [table: see text]. This compares to 801 procedures on the 1,033 patients in 1995: 552 US, 228 CT, and 21 DPL. Total cost was $254,316 for the 1993 group and $168,501 for the 1995 group. Extrapolated to a 1-year period, a significant (P < 0.05) cost savings of $171,630 would be realized. Cost per patient evaluated was significantly reduced from $285.75 in 1993 to $163.12 in 1995 (P < 0.05). This represents a 43 per cent reduction in per patient expenditure for evaluating the abdomen. By effectively utilizing ultrasonography in the evaluation of patients with blunt abdominal trauma, a significant cost savings can be realized. This effect results chiefly from an eight-fold reduction in the use of DPL, and a two-fold reduction in the use of CT.

Predialysis glycemic control is an independent predictor of clinical outcome in type II diabetics on continuous ambulatory peritoneal dialysis.

OBJECTIVE: To evaluate the correlation between predialysis glycemic control and clinical outcomes for type II diabetic patients on continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Sixty type II diabetic patients on CAPD were classified into 2 groups according to the status of glycemic control. In group G (good glycemic control), more than 50% of blood glucose determinations were within 3.3-11 mmol/L and the glycosylated hemoglobin (HbA1C) level was within 5-10% at all times. In group P (poor glycemic control), fewer than 50% of blood glucose determinations were within 3.3-11 mmol/L or HbA1C level was above 10% at least once during the follow-up duration. In addition to glycemic control status, predialysis serum albumin, cholesterol levels, residual renal function, peritoneal membrane function, and the modes of glycemic control were also recorded. SETTING: Dialysis Unit, Department of Nephrology of a single university hospital. PATIENTS: From February 1988 to October 1995, 60 type II diabetic patients receiving CAPD for at least 3 months were enrolled. MAIN OUTCOME MEASURES: Morbidities before and during the dialysis period, patient survival, and causes of mortality. RESULTS: The patients with good glycemic control had significantly better survival than patients with poor glycemic control (p < 0.01). There was no significant difference in predialysis morbidity between the two groups. No significant differences were observed in patient survival between the patients with serum albumin greater than 30 g/L and those with less than 30 g/L (p = 0.77), with cholesterol levels greater or less than 5.18 mmol/L (p = 0.73), and with different peritoneal membrane solute transport characteristics evaluated by peritoneal equilibration test (p = 0.12). Furthermore, there was no significant difference in survival whether the patients controlled blood sugar by diet or with insulin (p = 0.33). Cardiovascular disease and infection were the major causes of death in both groups. Although good glycemic control predicts better survival, it does not change the pattern of mortality in diabetics maintained on CAPD. CONCLUSIONS: Glycemic control before starting dialysis is a predictor of survival for type II diabetics on CAPD. Patients with poor glycemic control predialysis are associated with increased morbidity and shortened survival.