Impact of surgical site infections after open and laparoscopic colon and rectal surgeries on postoperative resource consumption.

PURPOSE: To estimate the impact of surgical site infection (SSI) on postoperative resource consumption for colon and rectal open and laparoscopic surgeries after accounting for infection depth and patient characteristics, and to compare these estimates among institutions. METHODS: We collected administrative and SSI-related data from eight Japanese hospitals, and used generalized linear models to estimate excess postoperative length of stay (LOS) and charges attributable to SSI. Covariates included wound class, American Society of Anesthesiologists (ASA) score, operation time, emergency, colostomy, trauma, implant, and comorbidities. RESULTS: We examined 1,108 colon surgery (CS) and 477 rectal surgery (RS) patients. For open surgery, the postoperative LOS in non-SSI patients was 13.5 (CS) and 15.9 days (RS). Compared with non-SSI patients, the postoperative LOS increased by 4.5 (CS) and 2.8 days (RS) for superficial SSI, 6.8 (CS) and 8.5 days (RS) for deep SSI, and 7.8 and 9.5 days for space/organ SSI. For laparoscopic surgery, the postoperative LOS was 9.8 (CS) and 14.6 days (RS). SSI was significantly associated with increased postoperative LOS for superficial SSI [by 4.8 (CS) and 3.6 days (RS)], deep SSI [by 10.3 (CS) and 23.9 days (RS)], and space/organ SSI [by 8.9 days (RS)]. The postoperative LOS among hospitals was 3.8-10.4 days (CS) and 1.3-12.2 days (RS). Postoperative SSI-attributable charges ranged from $386 to $2,873, depending on organ, procedure, and infection depth. CONCLUSION: This study quantified the impact of SSIs on resource consumption and confirmed significant cost variations among hospitals. These variations could not be explained by patient characteristics or infection type.

Desensitization with the Use of an Antibody Removal-Free Protocol in ABO-Incompatible Kidney Transplant Recipients with a Low Anti-A/B Antibody Titer.

BACKGROUND: Desensitization for ABO-incompatible (ABOi) kidney transplantation mainly comprises removal of antibodies with the use of apheresis and suppression of antibody (Ab) production with the use of rituximab. This study aimed to estimate the outcomes of ABOi kidney transplantation with the use of an Ab removal-free protocol to avoid complications associated with apheresis. METHODS: A total of 32 de novo consecutive adults who underwent ABOi living-donor kidney transplantation were retrospectively evaluated. Our protocol for ABOi recipients was stratified and fixed according to the anti-A/B Ab titer at baseline before desensitization. Desensitization was performed before transplantation with 0-4 sessions of plasmapheresis or double-filtration plasmapheresis and 1-2 administrations of rituximab at 100 mg/body. Graft outcomes, anti-A/B Ab titer, and plasma fibrinogen level were compared between the Ab removal (n = 21) and Ab removal-free (n = 11) groups. RESULTS: Between the Ab removal and Ab removal-free groups, the graft loss rate (4.8% vs 0.0%; P = 1.0), acute rejection rate (19.0% vs 0.0%; P = .14), and serum creatinine level (1.74 vs 1.40 mg/dL, P = .53) were similar. The anti-A/B Ab titer was maintained at a low level until postoperative month 12 in both groups. The plasma fibrinogen level on the operation day was significantly lower in the Ab removal group than in the Ab removal-free group (163.4 vs 250.2 mg/dL; P < .001). CONCLUSIONS: Desensitization with the use of an antibody removal-free protocol for ABOi kidney transplant recipients with a low anti-A/B Ab titer can maintain excellent graft outcomes and avoid postoperative bleeding risk.

Prevention of Late-Onset Cytomegalovirus Infection and Disease in Donor-Positive/Recipient-Negative Kidney Transplant Recipients Using Low-Dose Valganciclovir.

BACKGROUND: The main challenge with cytomegalovirus (CMV) prophylaxis in IgG donor-positive/recipient-negative (D+/R-) kidney transplant recipients is late-onset CMV disease. We evaluated a novel protocol for the prevention of late-onset CMV infection and disease in D+/R- organ recipients. METHODS: Our prospective, observational, cohort study included 100 adult kidney transplant recipients. Prophylaxis with low-dose valganciclovir (450 mg/d, 3 times a week for 6 months) was administered to D+/R- recipients. Risk factors for CMV infection and disease were identified. Renal function and the outcomes of CMV infection and disease were compared between D+/R- (n = 15) and recipient-positive (R+; n = 81) organ recipients. RESULTS: D+/R- recipients showed significant independent risk factors with high hazard ratios for CMV infection (2.04) and disease (10.3). The proportion of CMV infection in D+/R- and R+ recipients was 80% and 46% (P = .023), and that of CMV disease was 33% and 6.2% (P = .008), repectively. D+/R- recipients developed CMV infection and disease within 6 months after transplantation. However, both CMV infection- and disease-free survival rates beyond 1 year post-transplantation defined as late-onset were stable in D+/R- recipients. Moreover, serum creatinine levels at 1 year post-transplantation were comparable between D+/R- and R+ recipients (1.45 ± 0.71 vs 1.16 ± 0.35 mg/dL, P = .26). CONCLUSION: Our novel protocol prevented late-onset CMV infection and disease beyond 1 year post-transplantation in D+/R- recipients.

Steroid Withdrawal Using Everolimus in ABO-Incompatible Kidney Transplant Recipients With Post-Transplant Diabetes Mellitus.

BACKGROUND: The effectiveness of everolimus (EVR) for ABO-incompatible (ABOi) kidney transplantation is unknown. We evaluated outcomes of conversion from steroid to EVR in ABOi kidney transplant recipients. METHODS: We performed a retrospective observational cohort study of 33 de novo consecutive adult ABOi living donor kidney transplant recipients. Desensitization was performed using 0 to 4 sessions of plasmapheresis and 1 to 2 doses of 100 mg rituximab according to the anti-A/B antibody titer. ABOi recipients were administered a combination of tacrolimus, mycophenolate mofetil, and methylprednisolone. Diabetic patients were converted from methylprednisolone to EVR at 1 to 15 months post-transplantation to prevent diabetes progression. Graft outcomes, hemoglobin A1c (HbA1c) levels, and cytomegalovirus infection rates were compared between the EVR (n = 11) and steroid (n = 22) groups. RESULTS: Mean postoperative duration was 814 and 727 days in the EVR and steroid groups, respectively (P = .65). Between the 2 groups, graft survival rate (100% vs 95.5%, P > .99), acute rejection rate (9.1% vs 18.2%, P = .64), and serum creatinine levels (1.46 mg/dL vs 1.68 mg/dL, P = .66) were comparable. Although HbA1c levels were elevated in the steroid group (5.47%, 5.87%; P = .003), no significant deterioration was observed in the EVR group without additional insulin administration (6.10%, 6.47%; P = .21). Cytomegalovirus infection rate was significantly lower in the EVR group than in the steroid group (18.2% vs 63.6%, P = .026). CONCLUSION: Conversion from steroid to EVR in ABOi kidney transplant recipients maintained excellent graft outcomes and avoided diabetes progression and cytomegalovirus infection.

Effective and Safe Reduction of Conventional Immunosuppressants Using Everolimus in Maintenance Kidney Transplant Recipients.

BACKGROUND: Adverse events due to conventional immunosuppressive therapy decrease both graft and patient survival. We aimed to establish a new protocol using everolimus (EVR) to safely minimize conventional immunosuppressants in maintenance kidney transplant recipients. METHODS: A total of 86 consecutive kidney transplant recipients with no complications were maintained with triple-drug combination therapy (conventional group). In case of complications, the administration of very low-dose tacrolimus (C0: 5.0 to <3.0 ng/mL), reduced mycophenolate mofetil (1000-1500 to 500-1000 mg), and EVR (C0: 3.0-5.0 ng/mL) and methylprednisolone withdrawal (2-4 to 0 mg) were simultaneously conducted (EVR group). Graft survival and acute rejection rate were compared between groups. Within the EVR group, the dose of conventional immunosuppressants was compared between pre- and post-EVR administration. Renal function was evaluated 1 year post-EVR administration. RESULTS: All grafts survived in the conventional (n = 50) and EVR (n = 36) groups, and biopsy-proven acute rejection rate exhibited no significant difference between these groups (12% vs 17%; P = .55). Furthermore, no acute rejection occurred post-EVR administration. In the EVR group, all immunosuppressants significantly decreased post-EVR administration compared with those pre-EVR administration (P < .01), and serum creatinine significantly improved at postoperative year 1 (P = .031). CONCLUSIONS: EVR administration enables very low-dose tacrolimus administration, helps reduce mycophenolate mofetil and steroid withdrawal, and ameliorates renal function in maintenance kidney transplant recipients experiencing complications associated with conventional immunosuppressive therapy.

Selection Criteria for Kidney Laterality in Retroperitoneoscopic Living Donor Nephrectomy and the Usefulness of Pretransplant Intervention.

OBJECTIVES: To evaluate the selection criteria for kidney laterality and the usefulness of pretransplant intervention in living donor nephrectomy. METHODS: We compared conventional and revised criteria. The conventional criteria were that left kidneys were chosen in preference and provided the kidney with the fewest structural abnormalities and lowest functional decline and that most renal arteries remained in the donor. From April 2013, we allowed the use of left kidneys with double renal arteries. Patient characteristics and surgical outcomes were retrospectively compared between right and left retroperitoneoscopic living donor nephrectomies. RESULTS: We compared data for 30 right kidney and 222 left kidney nephrectomies. Right kidneys were selected because of multiple renal arteries (n = 18), structural abnormalities (n = 10) of the left kidney, or functional decline (n = 2) of the right kidney. Right retroperitoneoscopic nephrectomies were associated with significantly longer operating times (267 minutes vs 241 minutes), larger blood losses (240 g vs 55 g), and higher open conversion rates (10% vs 0.9%). Pretransplant intervention was necessary for structural abnormalities in right kidneys, but the amended selection criteria resulted in fewer right nephrectomies. Pretransplant intervention was still necessary by ex vivo arterial anastomosis for multiple left renal arteries, which increased the total ischemia time (94 minutes vs 64 minutes); however, post-transplantation renal function was not significantly different. CONCLUSIONS: Pretransplant intervention was beneficial both for repairing structural abnormalities and for reducing the difficulties of retroperitoneoscopic living donor nephrectomy.

Enhanced insulin response relates to acetylcholine-induced vasoconstriction in vasospastic angina.

OBJECTIVES: This study investigated whether insulin response to an oral glucose load correlates to acetylcholine-induced coronary vasoconstriction in subjects with vasospastic angina. BACKGROUND: It has been suggested that coronary vasospasm is caused by augmented vascular responsiveness possibly exerted by atherosclerosis. Recently, insulin resistance syndrome has been proposed as a major promotor of atherosclerotic disease, potentially enhancing vascular smooth muscular tone. METHODS: Among subjects with angiographically smooth coronary arteries, we selected 14 subjects with vasospastic angina and 14 age- and gender-matched subjects with atypical chest pain. We compared coronary vasomotor response to acetylcholine infusion, glucose and insulin responses to an oral glucose load (75 g), serum lipid concentrations, obesity, heart rate, blood pressure and smoking habits in both groups. RESULTS: Fasting serum insulin concentrations and insulin response were higher in subjects with vasospastic angina than in those with atypical chest pain; however, glucose tolerance, obesity, heart rate, blood pressure and smoking habits did not differ between groups. In subjects with vasospastic angina, nearly all coronary segments, except distal segments of the left circumflex coronary artery, were constricted at peak acetylcholine infusion (20 to 100 micrograms), whereas all segments were dilated in subjects with atypical chest pain. Regression analysis for both groups demonstrated a correlation between coronary vasoconstriction and fasting serum insulin concentrations (r = 0.52, p < 0.01), insulin response (r = 0.71, p < 0.001), serum triglyceride concentrations (r = 0.51, p < 0.05) and atherogenic index (r = 0.44, p < 0.05). CONCLUSIONS: Results show that acetylcholine-induced coronary vasoconstriction in subjects with vasospastic angina correlates with hyperinsulinemia and enhanced insulin response, suggesting insulin resistance syndrome as a feature of vasospastic angina.

Imidazolium crosslinks derived from reaction of lysine with glyoxal and methylglyoxal are increased in serum proteins of uremic patients: evidence for increased oxidative stress in uremia.

Glyoxal (GO) and methylglyoxal (MGO) are reactive dicarbonyl compounds formed during autoxidation of both carbohydrates and lipids. They may react with lysine and arginine residues of proteins in Maillard or browning reactions, yielding advanced glycation or lipoxidation end products. Among these are the imidazolium crosslinks, N,N(-di(N(epsilon)-lysino))imidazolium (glyoxal-lysine dimer, GOLD) and N,N(-di(N(epsilon)-lysino))-4-methyl-imidazolium (methylglyoxal-lysine dimer, MOLD). We have detected and measured GOLD and MOLD in human serum by electrospray ionization/mass spectrometry/mass spectrometry (ESI/MS/MS), using 15N4-GOLD and 15N4-MOLD as internal standards. In this report we show that levels of GOLD and MOLD are significantly elevated (3-4-fold, P< 0.01) in sera of non-diabetic uremic patients, compared to age-matched controls, and represent a major class of non-enzymatic, Maillard reaction crosslinks in plasma proteins. These results provide strong evidence for increased non-enzymatic crosslinking of tissue proteins by GO and MGO in uremia, implicating oxidative stress and resultant advanced glycation and lipoxidation reactions in tissue damage in uremia.

Health-related quality of life among renal-transplant recipients in Japan.

BACKGROUND: This study had four goals: (1) to evaluate an index of health-related quality of life (HQOL) among renal-transplant recipients in Japan, (2) to compare HQOL of renal-transplant recipients with that of the Japanese population as a whole, and (3,4) to study associations of HQOL with renal function and with the time since transplantation. METHODS: Questionnaires were distributed to 570 subjects. All were outpatients, were 16 years old or older, and were studied at least 1 year after they had received their latest renal transplant. HQOL was assessed with the Short Form 36-item health survey. Subjects' physicians provided data on renal function. Associations of HQOL with serum creatinine concentration and with the time since transplantation were evaluated by logistic regression. RESULTS: The response rate was 83%. Data from patients with diabetes and from those who had had at least two renal transplants were excluded; data from 395 recipients were analyzed. On the physical functioning, general health perception, vitality, and social functioning scales, the patients' scores were significantly lower than the Japanese national-norm scores. General health perception was particularly low. Serum creatinine concentrations were associated with general health perception, vitality, and social functioning. Longer times since transplantation were associated with better social functioning. CONCLUSIONS: Although social and physical functioning may improve after transplant surgery, a low self-rating of general health seemed to remain. The rarity of renal transplantation in Japan and other psychosocial factors may explain the low self-rating of general health in Japanese renal-transplant recipients.

Outcomes of hemodiafiltration based on Japanese dialysis patient registry.

Effectiveness of various therapeutic modalities was analyzed among 1,196 patients entered in the registry of the Japanese Society for Dialysis Therapy who were on hemopurification therapy as of the end of 1998 and developed dialysis-related amyloidosis during 1999. In the investigation, the effectiveness of various hemopurification modalities on the dialysis-related amyloidosis was ranked as exacerbation, unchanged, or alleviation, so as to analyze the possible relationship between the hemopurification modality and its effectiveness. The analysis was performed using a logistic regression approach, and the results were shown as "the risk of a worse therapeutic ranking" among the hemopurification modalities. The smaller "the risk of a worse therapeutic effect" was, the more effective the treatment modality. When the risk of a worse therapeutic effect for the hemodialysis patients treated by a regular membrane was put at 1.0, the risk for hemodialysis patients using high-flux membrane was 0.489, the off-line hemodiafiltration risk was 0.117, the on-line hemodiafiltration risk was 0.013, and the risk of push/pull hemodiafiltration was 0.017. For hemodialysis with a beta(2)-microglobulin adsorption column, a low risk of 0.054 was found. The results indicated that hemodiafiltration therapy and simultaneous hemodialysis with beta(2)-microglobulin adsorption therapy were more effective treatment for dialysis-related amyloidosis.

Health-related quality of life among dialysis patients in Seattle and Aichi.

We used the 36-item Short-Form Health Survey to compare health-related quality of life (HRQOL) between 104 dialysis patients in Seattle, WA, and 2,178 patients in Aichi, JAPAN: Compared with Aichi patients, Seattle patients had lower scores on three scales related to physical HRQOL: Physical Functioning (PF; P = 0.03), Role-Physical (RP; P = 0.004), and Vitality (VT; P < 0.001). However, scores related to mental HRQOL were higher for Seattle patients compared with those of Aichi patients, which included scores for Role-Emotional (RE; P = 0.005) and Mental Health (MH; P < 0.001). Scores for Bodily Pain, General Health Perception, and Social Functioning did not differ significantly between the two groups. These differences persisted even after potential confounding factors were controlled for. However, after taking into account national norm data for the United States and Japan, differences in PF and VT disappeared, whereas differences in RP, RE, and MH persisted. These results suggest that the higher scores for PF and VT in Aichi patients were partly explained by the higher physical HRQOL of the Japanese general population. Although these data may not be representative of the total dialysis populations in the United States and Japan, they suggest potential differences in HRQOL between patients in the two countries. Additional research is needed to confirm these results and understand the factors associated with these differences. The findings suggest the need for further attention to the physical limitations of US dialysis patients and the mental health of Japanese dialysis patients.

Increased serum midkine levels during hemodialysis using heparin in chronic renal failure.

The heparin-binding growth factor midkine (MK) has been implicated in neuron growth, angiogenesis, and inflammation. In this study, to elucidate the involvement of MK in the development of pathologies associated with uremia, we examined the serum MK levels in patients receiving hemodialysis (HD) by a highly sensitive enzyme-linked immunoassay. Although no significant difference was found between control serum and serum before dialysis in HD patients, serum MK levels increased significantly at the early stage of HD sessions using heparin and gradually decreased after dialysis. In normal controls, intravenous administration of heparin induced a similar sudden increase of MK, but the subsequent decrease was also rapid. In an in vitro study, MK was released in time- and heparin-dose dependent manner from cultured vessels, but not from peripheral leukocytes. These results indicate that, in HD patients, MK is released mainly from endothelial cells immediately after administration of heparin during HD and disappears gradually from blood due to renal impairment. This phenomenon might affect some complications associated with HD.

Variable expression of heparan sulfate epitopes in crescents of human glomerulonephritis.

Crescentic glomerulonephritis leads to a rapid loss of renal function. Although glomerular crescents are rich in extracellular matrix (ECM), the composition and genesis of the ECM are incompletely understood. Heparan sulfate (HS) is a major ECM molecule and has polymeric structure of great variability. Recent findings that alterations in HS epitopes are associated with renal pathology prompted us to hypothesize that specific HS epitopes might be expressed in the evolution of crescents. We reviewed clinical records of 724 patients who underwent renal biopsy and found 21 patients with rapidly progressive glomerulonephritis. Immunohistochemistry was performed using monoclonal antibodies (mAbs) against well-defined HS epitopes. One mAb was directed against unsaturated uronic acid residues generated during the selective removal of HS by heparitinase (a), and a further two different mAbs against N-sulfate-enriched and O-sulfate-poor portions of HS (b). Results showed that mAb (a) reacted to ECM of normal, sclerosed and crescentic glomeruli and that mAbs (b) reacted strongly to ECM of fibrocellular crescents but not to fibrous crescents, the periglomerular areas and noncrescentic intraglomerular areas. We concluded there are regional differences in HS epitope expression, although HS are ubiquitous components of glomerular ECM. N-sulfate-enriched and O-sulfate-poor portions of HS might play a role in crescent formation.

Basic fibroblast growth factor-heparan sulphate complex in the human dialysis-related amyloidosis.

A major constituent of the amyloid fibrils in dialysis-related amyloidosis is beta 2-microglobulin (beta 2-MG). Heparan sulphates (HS) co-localize with the amyloid fibrils and monocytes/macrophages are commonly found around amyloid deposits, but the role of HS in amyloidogenesis is not yet defined. HS have variable saccharide sequences and can interact specifically with basic fibroblast growth factor (bFGF), a potent chemotactic factor for the monocyte/macrophage. The present investigation was undertaken to look for a functional link between co-localized HS and the pathogenesis of dialysis-related amyloidosis. Using amyloid-enriched ligament, immunohistochemical localization was tested for beta 2-MG, endogenous bFGF, and bFGF-binding portions of HS. For the detection of bFGF-binding portions of HS, the ligament sections were incubated with exogenous bFGF and then with anti-bFGF antibody. The specificity of the interaction between bFGF and HS was established by confirming a concomitant loss of immunoreactivity during selective removal of HS with heparitinase. beta 2-MG, endogenous bFGF, and bFGF-binding portions of HS were detected between bundles of collagen. Endogenous bFGF and bFGF-binding portions of HS were not detected in more advanced amyloid lesions, whereas beta 2-MG and other portions of HS were detected. We propose that beta 2-MG, endogenous bFGF, and bFGF-binding portions of HS form a complex and localize in the early amyloid lesions of dialysis-related amyloidosis.

Cardioprotective effects of troglitazone in streptozotocin-induced diabetic rats.

Troglitazone, a new oral antidiabetic agent, shows hypoglycemic effects in insulin-resistant animal models and humans. This study was conducted to evaluate the effects of troglitazone on the heart of diabetic animals. Streptozotocin (STZ)-induced diabetic rats and age-matched controls were treated with troglitazone as a 0.2% food admixture for 6 weeks. Basal and postischemic cardiac functions at 14 weeks of age were then examined in isolated working heart. Troglitazone treatment did not attenuate the insulinopenia and hyperglycemia of diabetic rats, but it partially improved the hypertriglyceridemia. Troglitazone treatment partially restored the basal heart rate and cardiac work of diabetic rats to nearly control values. Troglitazone also improved the postischemic functional deficits of diabetic rats: heart rate (untreated 61% of baseline at 30-minute reperfusion v treated 92%, P < .001), left ventricular (LV) developed pressure (54% v 94%, P < .001), peak positive ([LV + dP/dt] 54% v 93%, P < .001) and negative ([LV -dP/dt] 53% v 94%, P < .001) first derivative of LV, and cardiac work (44% v 98%, P < .001). Diabetic animals showed ultrastructural damage including disarray of sarcomere, disorganization of mitochondrial matrix, cytoplasmic vacuolization, and invagination of nuclear membrane; these were partially normalized by troglitazone treatment. Our results suggest that troglitazone treatment has a cardiprotective effect on the basal and postischemic cardiac function of STZ-induced diabetic rats.

A mechanism of pathogenicity of "Streptococcus milleri group" in pulmonary infection: synergy with an anaerobe.

The relationship between Streptococcus constellatus, one of the species of the "Streptococcus milleri group", and Prevotella intermedia was studied in a model of pneumonia in mice and in vitro to elucidate mechanisms of pathogenicity in "S. milleri group"-associated pulmonary infection. Acute pneumonia with or without empyema and lung abscess in mice with mixed infection resulted in 60% mortality rate, but there was only 10% mortality and mild pneumonia in each separate infection. Bacterial clearance of organisms, especially S. constellatus, in mixed infection was delayed. Enhancement of growth of S. constellatus was demonstrated when cultured with P. intermedia; growth was also stimulated by a culture filtrate of P. intermedia which also inhibited bactericidal activity of human neutrophils. In an examination of infectivity and bacterial clearance of S. constellatus with P. intermedia culture filtrate in vivo, there was 20% mortality and delayed clearance of S. constellatus, although the infection was not as severe as that produced by the combination of both organisms. These results suggest that P. intermedia may act with S. constellatus in the production of pulmonary infections by stimulating its growth and suppressing bactericidal activity of the host.

Purification and characterization of perlecan fragment in urine of end-stage renal failure patients.

We found a new spot on the two-dimensional electrophoresis pattern of the urine protein from hemodialysis patients. In order to identify the protein forming this new spot, the protein was purified by five steps of chromatography. It was shown that the amino acid sequence of this new protein from the N-terminal to the 20th amino acid was identical with the sequence from the 4197th to 4216th amino acid of perlecan, which is the core protein of the proteoglycan localizing in the systemic capillary basement membranes. It was also found that the molecular weight (25,000 daltons) of this new protein was comparable to the calculated molecular weight of the molecular region of the perlecan from the 4197th amino acid to the C-terminal. Lastly, it was shown that the antibodies against this new protein reacted with the perlecan produced by human fibroblasts. All these findings indicated that the new protein is a perlecan fragment.

Enhancement of postischemic myocardial stunning by calcium overload in hearts of diabetic rats.

The effects of Ca2+ concentration on postischemic myocardial stunning were studied in isolated working hearts of rats with streptozotocin-induced diabetes and of age-matched control rats. During reperfusion after 10 min of ischemia, hearts from control rats showed complete recovery of cardiac function of Ca2+ concentrations of 1.25, 1.88, and 2.50 mmol/L, while the recovery of diabetic rats was decreased only at a Ca2+ concentration of 2.50 mmol/L. Although myocardial Na+ and Ca2+ concentrations were comparable between control and diabetic rats, only diabetic rats showed increases in myocardial concentration of Na+ during ischemia and Ca2+ during reperfusion at a Ca2+ concentration of 2.50 mmol/L. Results suggest that diabetic rat hearts are vulnerable to postischemic stunning via an overload of calcium.

Some new aryl-sydnones: effects on murine tumours.

The effects of new aryl-sydnones: 3-[4-X-3-nitrophenyl]-1,2,3-oxadiazolium-5-olates, where X = Cl (SYD-1); pyrrolidino (SYD-2); piperidino (SYD-3) and morpholino (SYD-4) on the survival of mice bearing Sarcoma 180, Ehrlich carcinoma, B10MCII (Fibrous histiocytoma) and L1210 leukemia ascitic tumours, on the proliferation of cultured tumour cells and on the synthesis of DNA in L1210 leukemia were determined. SYD-1 and SYD-2 in vivo significantly enhanced the survival of S180, Ehrilich and B10MCII tumour-bearing mice. Furthermore, SYD-2 showed significant activity against L1210. SYD-3 and SYD-4 did not show antitumour activity. SYD-1, in vitro was the most cytotoxic against all the above tumour cells. All of the drugs tested inhibited thymidine uptake by L1210 cells, SYD-4 being the least active.

Growth control of experimental tumor by syngeneic thymocyte extracts.

The effect of cell-free extracts obtained from thymocytes of 8, 18 and 23 day fibrosarcoma-bearing U rats and normal U rats on tumor growth was investigated. The results show that thymocyte extracts of 8 day tumor-bearing rats inhibit the tumor growth in implanted animals and no significant effect was found with extracts from other times, or from normal thymocytes. Some of the inhibitory activity was lost by dialysis, which led us to assume that low molecular weight substances are involved in the antitumor immune response.