Spiramycin,Oxytetracycline and Sulphamonomethoxine Contents of Eggs and Egg-Forming Tissues of Laying Hens

Spiramycin (SP), oxytetracycline (OTC) or sulphamonomethoxine (SMM) was fed to laying hens at a dietary level of 400 p.p.m. for 7 successive days. After 7 days of medicated feed, the concentrations of SP, OTC and SMM were determined in the blood, liver, ovary, oviducts (magnum and isthmus plus shell gland) and eggs (albumen and yolk) by high-performance liquid chromatography. Of the three drugs, OTC showed the lowest content in the above tissues and eggs, while the reverse was true for SMM. Low concentrations of SP were measured in the blood, whereas contents in the liver and the oviducts were relatively much higher.     

Levels of Retinol and Retinyl Esters in Plasma and Urine of Dogs with Urolithiasis

Vitamin A (VA) deficiency and Tamm‐Horsfall glycoprotein (THP), a protein that binds retinol and retinyl esters in canine urine, might be involved in the pathogenesis of urolithiasis in dogs. In the present study, we assessed levels of retinol, retinyl esters, retinol‐binding protein (RBP) and THP in plasma and urine of dogs with a history of urolithiasis (n = 25) compared with clinically healthy controls (n = 18). Plasma retinol concentrations were higher in dogs with uroliths of struvit (P < 0.01), calcium oxalate (P < 0.05), urate (P < 0.01) and cysteine, but there were no differences in the concentrations of plasma RBP and retinyl esters. Excretion of urinary retinol and retinyl esters were tentatively, but not significantly higher in the stone‐forming groups, which was accompanied by increased levels of urinary RBP (P < 0.01) and lower excretions in THP (P < 0.01). The results show that VA deficiency may be excluded as a potential cause for canine urolithiasis. However, the occurrence of RBP and a concomitant reduction of THP in urine indicates a disturbed kidney function as cause or consequence of stone formation in dogs.     

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on testicular spermatogenesis-related panels and serum sex hormone levels in rats

OBJECTIVES

To determine the detrimental role of tetrachlorodibenzo‐p‐dioxin (TCDD) in testicular histology, spermatogenesis‐related panels and proteome, and serum sex hormone levels.

MATERIALS AND METHODS

In all, 40 male rats were divided into equal groups: a normal control (NC) group that received vehicle and saline, and a TCDD‐treated (TT) group injected intraperitoneally with TCDD (one dose, 50 µg/kg body weight). The rats were killed 4 weeks after TCDD exposure and testicular weight, histopathology, proteome and variables related to spermatogenesis, and serum sex hormone levels were investigated.

RESULTS

TCDD induced a significant decrease in testicular weight, Johnsen’s score, seminiferous tubular size, percentage of tubules containing sperm, sperm counts, germ cell counts and Sertoli cell index. In addition, there was a significant decrease in serum testosterone level (P < 0.01) and a remarkable increase in oestradiol (P < 0.01), follicle‐stimulating hormone (P < 0.05) and luteinizing hormone (P < 0.05) levels in the TT group. The expression of six testicular proteins including testis‐specific heat shock protein (Hsp70), protein disulphide isomerase A3 precursor, 3‐phosphoglycerate dehydrogenase, nonmuscle myosin heavy‐chain type B‐like protein, and superoxide dismutase 1 were significantly up‐regulated (P < 0.05–0.01). Interestingly, fertility protein SP22 and phosphatidylethanolamine‐binding protein were down‐regulated but this was only significant for fertility protein SP22 (P < 0.05).

CONCLUSION

TCDD induces marked histological changes in the testis, impairs variables related to spermatogenesis, and increases serum oestradiol levels but decreases testosterone levels. In particular, TCDD disturbs testicular proteome profiles in rats.     

In Vitro Hepatobiotransformation of Sulphadimethoxine in Laying Hens

The biotransformation of sulphadimethoxine (SDM) was estimated in liver post‐mitochondrial supernatants (S‐9) from laying hens. The pathway and activity for hen S‐9 were compared with those for cow and pig S‐9. The formation of the hydroxylation of SDM, 6‐hydroxy SDM (6‐OH‐SDM), was found only with hen S‐9. The N₄‐acetylating activity of SDM in hen S‐9 was lower than in cow and pig S‐9. All S‐9 from the three species de‐acetylated N₄‐acetyl SDM (N₄‐AcSDM). With respect to the hydroxylation and N₄‐acetylation rates in hen S‐9, the values incubated at 41°C were higher than those at 37°C (P < 0.01).     

Innate immune molecule surfactant protein D attenuates sepsis‐induced acute kidney injury through modulating apoptosis and NFκB‐mediated inflammation

The objective of this study is to investigate the mechanism whereby innate immune molecule surfactant protein D (SP‐D) attenuates sepsis‐induced acute kidney injury (AKI) through modulating apoptosis and nuclear factor kappa‐B (NFκB)‐mediated inflammation. In the present study, a mouse sepsis model was established by cecal ligation and puncture in SP‐D knockout (KO) mice and wild‐type (WT) mice. A sham‐operated group was included as the control. The experimental materials were extracted 6 and 24 hours postoperatively. The plasma levels of tumour necrosis factor alpha (TNF‐α) and MCP‐1 were determined by enzyme‐linked immunosorbent assay (ELISA). Apoptosis was measured by double staining with Annexin V/propidium iodide and flow cytometry. The levels of NFκB in renal tissues were measured by ELISA and Western blotting assay. Apoptosis was detected by TUNEL assays. There were no significant differences in plasma TNF‐α levels between the WT sham group and the KO sham group at 6 and 24 hours postoperatively (P < .05), but the levels of TNF‐α in the WT sepsis and KO sepsis groups were significantly higher than those in controls (P < .05). The levels of TNF‐α in the KO sepsis group were significantly higher than those of the WT sepsis group (P < .05). TNF‐α levels in the WT sepsis group and the KO sepsis group at 24 hours postoperatively were significantly higher than those at 6 hours postoperatively (P < .05). The levels of MCP‐1 in the WT sepsis group and the KO sepsis group at 6 and 24 hours postoperatively were significantly higher than those in the control group (P < .05), and MCP‐1 levels in the KO sepsis group were significantly higher than those in the WT sepsis group (P < .05). MCP‐1 levels in the WT sepsis group and the KO sepsis group at 24 hours postoperatively were significantly higher than those at 6 hours postoperatively (P < .05). The expression of SP‐D in WT kidneys was significantly lower at 6 and 24 hours postoperatively (P < .05). The number of TUNEL‐positive cells in the kidneys from septic SP‐D KO mice was significantly higher (P < .05). The levels of NFκB in septic mice were significantly increased at 6 and 24 hours after induction of sepsis compared with the sham‐operated group compared with those of septic SP‐D KO mice and WT mice (P < .05). Innate immune molecule SP‐D significantly decreased plasma levels of inflammatory cytokines in mice and attenuated sepsis‐induced AKI by inhibiting NFκB activity and apoptosis.     

Short ileal segment for orthotopic neobladder: A feasibility study

Objectives: The objective of this study was to present the construction of a neobladder with a modified pouch technique using 25–35 cm of terminal ileum. Methods: Thirty‐eight patients whose pouch was constructed from 25–35 cm of terminal ileum (short pouch [SP] group) were prospectively evaluated vs 41 patients whose pouch was constructed from 50–70 cm of terminal ileum (long pouch group). Pouch volume, post‐void residual (PVR) volume, need for catheterization, continence and voiding frequency were evaluated at 3 and 12 months after surgery. Results: SP group patients had significantly smaller pouch capacity (440 vs 840 mL, P < 0.001) at month 12, and smaller PVR at postoperative months 3 (11 [0–43]vs 40 [0–147] mL, P < 0.001) and 12 (10 [0–90]vs 72 [0–570] mL, P < 0.001). SP group patients had significantly higher voiding frequency on postoperative month 3 (10 vs 9, P < 0.001) and 12 (7 vs 6, P < 0.005). Continence was significantly improved in the SP group compared with the long pouch group after 12 months (63.2% vs 34.1%, respectively, P = 0.034). Full continence improved significantly over time (P < 0.001) in the SP group, from 26.3% at month 3 to 63.2% at month 12. Conclusion: A pouch constructed from 25–35 cm of terminal ileum provides adequate capacity, smaller PVR, satisfactory continence and a better 24‐h voiding frequency pattern during the first postoperative year.     

Prospective Evaluation of the Change of Predialysis Protein‐Bound Uremic Solute Concentration With Postdilution Online Hemodiafiltration

Although protein‐bound uremic compounds have been related to outcome in observational studies, few current dialysis strategies provide more removal of those compounds than standard hemodialysis. We evaluated the evolution of protein‐bound uremic solutes after a switch from high‐flux hemodialysis to postdilution hemodiafiltration (n = 13). We compared predialysis solute concentration at 4, 5, and 9 weeks versus baseline for several protein‐bound compounds and water‐soluble solutes, as well as for β₂‐microglobulin. After 9 weeks of postdilution hemodiafiltration, a significant decrease versus baseline could be detected for total concentration of protein‐bound solutes: p‐cresylsulfate (3.98 ± 1.51–3.17 ± 1.77 mg/dL, ?20%, P < 0.01) and 3‐carboxyl‐4‐methyl‐5‐propyl‐2‐furanpropionic acid (0.72 ± 0.52–0.64 ± 0.46 mg/dL, ?11%, P < 0.01). For the other protein‐bound solutes, hippuric acid, indoleacetic acid, and indoxylsulfate, no change in total concentration could be detected. The concentration of the middle molecule, β₂‐microglobulin, decreased as well after 9 weeks of postdilution hemodiafiltration (24.7 ± 9.3–18.1 ± 6.7 mg/L, ?27%, P < 0.01). For water‐soluble compounds, no significant change of concentration was found. Postdilution hemodiafiltration in comparison to high‐flux hemodialysis provided significant reduction of predialysis concentration of protein‐bound compounds, especially those with the highest protein binding, and of β₂‐microglobulin, by ?11 to ?27% in 9 weeks.     

Comparison of the prognostic value of tumour‐ and patient‐related factors in patients undergoing potentially curative surgery for colon cancer

Aim To comprehensively compare the prognostic value of tumour‐ and patient‐related factors in patients undergoing curative surgery for colon cancer. Method From a database of 287 patients who underwent elective resection between 1997 and 2005, tumour factors including stage and host factors including systemic inflammatory response [modified Glasgow Prognostic Score (mGPS)] were identified. Results Median follow‐up was 65 months. Over this period, 125 patients died, 80 from cancer. On multivariate analysis of all significant patient and tumour related factors, Dukes stage (P < 0.01), vascular invasion (P < 0.01) and the mGPS (P < 0.01) were independently associated with cancer‐survival. Of the patient‐related factors, age (P < 0.01), haemoglobin (P < 0.01), white‐cell (P < 0.01), neutrophil (P < 0.01) and platelet (P < 0.01) counts, and alkaline phosphatase (P < 0.01) were most significantly associated with the mGPS. Conclusion In addition to tumour‐related factors such as Dukes stage and vascular invasion, the preoperative mGPS should be included to guide prognosis in patients undergoing curative resection for colon cancer.     

Clinical Validation of a New Immunoradiometric Assay for Intact Human Osteocalcin

The purpose of this study was to estimate clinical validity of a new available immunoradiometric assay for circulating intact human BGP (N-tact Osteo SP) by measuring this protein in a large number of normal subjects and patients with the most common metabolic bone diseases. One hundred normal subjects were studied in order to obtain our normal ranges (4.9 ± 1.7 ng/ml). The mean values found in 28 patients with primary hyperparathyroidism (17.5 ± 22.8 ng/ml, P < 0.001), 15 glucocorticoid-treated patients (1.9 ± 1.5, P < 0.001), 10 patients with hypoparathyroidism (1.5 ± 0.7, P < 0.001), 9 with hyperthyroidism (8.3 ± 3.8, P < 0.001), 8 with skeletal metastases (7.2 ± 2.3, P < 0.001), and 4 with humoral hypercalcemia of malignancy (2.42 ± 1.91, P < 0.005) were significantly different from mean values found in normal subjects. Mean decrease of serum osteocalcin T-score values was significantly greater when evaluated by N-tact Osteo SP assay in 15 steroid-treated patients (−1.4 ± 1.0) and 19 primary hyperparathyroid (PHPT) patients (3.6 ± 1.9), compared with the mean values obtained with the Elsa-Osteo assay (−0.67 ± 1.2, P < 0.002 and 4.3 ± 2.8, P < 0.04, respectively). We found significant correlations between the global skeletal uptake of 99mTc-methylendiphosphonate and serum BGP levels assayed by both N-tact Osteo SP (P < 0.01) and Elsa-Ost-Nat assay (P < 0.05). Our results indicate that this new immunoradiometric assay for the intact human osteocalcin has the potential for good discrimination between normal subjects and patients with both low and high bone turnover. Furthermore, our findings emphasize the fact that, in the absence of available standardized commercial assays, one should rely on only one assay because different results are obtained by different assays under different clinical conditions. Received: 22 January / Accepted: 22 September 1998     

Peritoneal Albumin Dialysis as a Novel Approach for Liver Support: Study in a Porcine Model of Acute Hepatic Failure

Artificial liver support gained considerable interest in recent years due to the development of various albumin dialysis systems, which prolong survival of some patients with acute liver failure (ALF). Τhis study aims to examine the role of peritoneal albumin dialysis in a postoperative ALF model. ALF was induced in 14 female Landrace pigs by a combination of major liver resection (70–75% of total parenchyma) and ischemic‐reperfusion injury on the liver remnant. Animals were randomly divided in two groups (n = 7 each). Both were monitored for 12 h of reperfusion and received peritoneal dialysis for 6 h, beginning 6 h after reperfusion. The albumin group received an albumin‐rich solution and the control group received albumin‐free solution. The control group gradually developed intracranial hypertension, whereas, in the albumin group, rise in the intracranial pressure was substantially attenuated (P < 0.01, t = 12 h). Albumin‐treated animals had significantly lower levels of ammonia (P < 0.01), total bile acids (P < 0.01), free fatty acids (P < 0.05), lactate (P < 0.01), and total bilirubin (P < 0.05). Liver malondialdehyde and protein carbonyl were significantly reduced (P = 0.007 and P = 0.001 at t = 12 h) after albumin dialysis. Results suggest that this method may become a useful adjunct in the management of ALF, thus, justifying further study.     

Factors influencing outcome of simultaneous kidney and pancreas transplantation: a 23-year single-center clinical experience

Introduction

Simultaneous kidney and pancreas transplantation (SKPT) has become an effective treatment for patients who have diabetes mellitus type I with advanced nephropathy. This study assesses the progress of the SKPT program at Uppsala University Hospital, Sweden, and evaluates prognostic factors for graft survival.

Materials and Methods

Between February 1986 and September 2009, we performed 113 SKPT. The immunosuppression protocols changed over time and are defined as era 1, cyclosporine (CyA), atzathioprine (AZA) and steroids (C/A/S); era 2, C/A/S with antithymocyte globulin (ATG) induction (C/A/S/A); era 3, CyA, mycophenolate mofetic (MMF), steroids and ATG induction (C/M/S/A); era 4, tacrolimus (TAC), MMF, steroid, and ATG induction (T/M/S/A) and era 5, TAC, MMF, steroids and basiliximab induction (T/M/S/B). We analyzed donor/recipient/operative and postoperative variables to assess their influence on pancreas graft and patient survivals.

Results

The overall 1-, 5-, and 10-year patient survivals were 95.5%, 84.1%, and 65.5%, respectively. The 1-, 5-, and 10-year overall pancreas graft survivals were 77.6%, 58.4%, and 48.4%. The 1-, 5-, and 10-year pancreas graft survivals in SKPT patients transplanted between October 1997 and September 2009. (T/M/S/A and T/M/S/B; eras 4 and 5) were 95.3%, 72.7%, and 63.1%, respectively, which was significantly better than those of patients transplanted between February 1986 and September 1997 (era, 1 through 3) (P < 0.01, P < 0.0001, respectively). The quadruple regimen with TAC and MMF (eras 4 and 5) decreased the incidence of acute rejection episodes compared with eras 1 through 3 (P < 0.0001). Basiliximab induction (T/M/S/B; era 5) reduced the CMV infection rate compared with eras 1 through 4 (P < 0.01). Multivariate analysis revealed that donor age (younger than 40 years), immunosuppressive regimen with TAC and MMF (eras 4 and 5), and absence of acute rejection episodes independently affected pancreas graft survival.

Conclusions

We demonstrate a superiority of the quadruple protocol with T/M/S/B for graft and patient survival with a decreased incidence of CMV infection after SKPT.     

Failure to remove de novo donor‐specific HLA antibodies is influenced by antibody properties and identifies kidney recipients with late antibody‐mediated rejection destined to graft loss – a retrospective study

Current research is focusing on identifying bioclinical parameters for risk stratification of renal allograft loss, largely due to antibody‐mediated rejection (AMR). We retrospectively investigated graft outcome predictors in 24 unsensitized pediatric kidney recipients developing HLA de novo donor‐specific antibodies (dnDSAs), and treated for late AMR with plasmapheresis + low‐dose IVIG + Rituximab or high‐dose IVIG + Rituximab. Renal function and DSA properties were assessed before and longitudinally post treatment. The estimated GFR (eGFR) decline after treatment was dependent on a negative % eGFR variation in the year preceding treatment (P = 0.021) but not on eGFR at treatment (P = 0.74). At a median follow‐up of 36 months from AMR diagnosis, 10 patients lost their graft. Altered eGFR (P < 0.001) and presence of C3d‐binding DSAs (P = 0.005) at treatment, and failure to remove DSAs (P = 0.01) were negatively associated with graft survival in the univariable analysis. Given the relevance of DSA removal for therapeutic success, we analyzed antibody properties dictating resistance to anti‐humoral treatment. In the multivariable analysis, C3d‐binding ability (P < 0.05), but not C1q‐binding, and high mean fluorescence intensity (P < 0.05) were independent factors characterizing DSAs scarcely susceptible to removal. The poor prognosis of late AMR is related to deterioration of graft function prior to treatment and failure to remove C3d binding and/or high‐MFI DSAs.     

Differential risks for adverse outcomes 3 years after kidney transplantation based on initial immunosuppression regimen: a national study

We examined integrated national transplant registry, pharmacy fill, and medical claims data for Medicare‐insured kidney transplant recipients in 2000–2011 (n = 45 164) from the United States Renal Data System to assess the efficacy and safety endpoints associated with seven early (first 90 days) immunosuppression (ISx) regimens. Risks of clinical complications over 3 years according to IS regimens were assessed with multivariate regression analysis, including the adjustment for covariates and propensity for receipt of a nonreference ISx regimen. Compared with the reference ISx (thymoglobulin induction with tacrolimus, mycophenolate, and prednisone maintenance), sirolimus‐based ISx was associated with significantly higher three‐year risks of pneumonia (adjusted hazard ratio, aHR 1.45; P < 0.0001), sepsis (aHR 1.40; P < 0.0001), diabetes (aHR 1.21; P < 0.0001), acute rejection (AR; adjusted odds ratio, aOR 1.33; P < 0.0001), graft failure (aHR 1.78; P < 0.0001), and patient death (aHR 1.40; P < 0.0001), but reduced skin cancer risk (aHR 0.71; P < 0.001). Cyclosporine‐based IS was associated with increased risks of pneumonia (aHR 1.17; P < 0.001), sepsis (aHR 1.16; P < 0.001), AR (aOR 1.43; P < 0.001), and graft failure (aHR 1.39; P < 0.001), but less diabetes (aHR 0.83; P < 0.001). Steroid‐free ISx was associated with the reduced risk of pneumonia (aHR 0.89; P = 0.002), sepsis (aHR 0.80; P < 0.001), and diabetes (aHR 0.77; P < 0.001), but higher graft failure (aHR 1.35; P < 0.001). Impacts of ISx over time warrant further study to better guide ISx tailoring to balance the efficacy and morbidity.     

Semen quality in men with chronic kidney disease and its correlation with chronic kidney disease stages

The aim of this study was to assess whether chronic kidney disease (CKD) has any impact on semen quality parameters in men with CKD stage 1–5. Results were collected from 66 men with different CKD stages (age 18–50 years). Age and BMI (body mass index) were recorded for each male. Higher CKD stage had a significant negative linear trend on semen volume (P < 0.05), progressive motility (P < 0.01), nonprogressive motility (P < 0.001), sperm concentration (P < 0.01), total sperm number (P < 0.01), cytoplasmic droplets (P < 0.01), teratozoospermia index (P < 0.05) and accessory gland markers, α‐glucosidase activity (P < 0.05), zinc (P < 0.01) and fructose (P < 0.01). BMI per se had no significant effect on semen volume, sperm number, sperm concentration, morphology, α‐glucosidase activity, fructose concentration or zinc level. A significant negative correlation between BMI and sexual‐hormone‐binding globulin (SHBG) (P < 0.01) was observed but not with other sex hormones. Age per se was related to a significant decrease of sperm concentration (P < 0.05), normal forms (P < 0.01) and testosterone level (P < 0.05). Our results indicate that CKD stage per se is a factor determining the number of spermatozoa available in the epididymis for ejaculation, in part independent of age‐related decrease of testosterone level and BMI.     

Effect of Seminal Plasma Fractions on Stallion Sperm Survival after Cooled Storage

This study aimed to evaluate stallion sperm survival after 24 h of cooled storage in the presence of seminal plasma (SP) derived from the sperm‐rich fractions (SRF) or sperm‐poor fractions(SPF) of the ejaculate, without SP, or in the presence of SP from other stallions. Ejaculates were collected from four stallions using an automated phantom, which separated the semen into five cups. Centrifuged and washed spermatozoa from cup 2 (SRF) were mixed with skim milk extender to a concentration of 100 × 10⁶ sperm/ml and then 1:1 (v/v) with SP from the stallion's own or another stallions’ second (SP‐SRF) or last cup (SP‐SPF). Skim milk extender (K) and skim milk extender supplemented with modified Tyrode's medium (KMT) were used as control treatments. After a 24‐h storage period in a transport container, spermatozoa were evaluated for motion characteristics and plasma membrane integrity by calcein acetoxymethyl (AM)/propidium iodide staining. The percentage of spermatozoa with intact plasma membranes after storage was lower in SP‐SRF than in SP‐SPF, and the highest in K (P < 0.05). Progressive motility (PMOT) was lower for sperm stored in SP‐SRF than for sperm stored in SP‐SPF (P < 0.05), but there was no significant difference in total motility (TMOT). Sperm stored in KMT (P < 0.05) registered the highest TMOT and PMOT percentages. Osmolarity was significantly higher and pH lower in K than in KMT or SP. Treatment with SP‐SPF from three stallions benefited the PMOT of sperm from one stallion. These preliminary findings suggest that SP from SRFs may be more harmful during storage than SP from SPFs. Removal of SP improves sperm survival in KMT extender, and exchanging SP between stallions seems to influence sperm survival.     

Seminal plasma stimulates cytokine production in endometrial epithelial cell cultures independently of the presence of leucocytes

We examined the effects of normal and leucocyte-positive semen on cytokine expression in endometrial epithelial cell cultures. Cytokines in pooled seminal plasma (SP) samples of men with normal semen parameters without (n = 9) and with leucocytospermia (LCS) (n = 9) were determined. Cultures of epithelial endometrial cells of women (n = 7) in the secretory phase were incubated with 10% SP for 24 h. Cytokines in culture supernatants and mRNA concentrations in the cultured cells were determined. Mean concentrations of interleukin (IL)-1β and transforming growth factor (TGF)-β1 were significantly higher (P < 0.05) in culture media with SP of men with normal semen parameters and LCS compared with control. Accordingly, a significant increase (P < 0.05) in mRNA concentrations (amol ml⁻¹) of IL-1β and TGF-β1 could be detected. The mean TGF-β1 and IL-1β concentrations in the culture supernatant with 10% SP from patients with normal semen parameters were 24-fold (P < 0.05) and 2-fold higher respectively when compared with control. The mean protein concentration of TGF-β1 measured in the supernatant with SP of men with LCS was not significantly reduced as compared with the supernatant with normal SP. In conclusion, our experiments support the concept of an endometrial sensitation effect by semen.     

The effect of Staphylococcus aureus on apoptosis of cultured human osteoblasts

Objective: To investigate the effect of Staphylococcus aureus (S. aureus) on cultured human osteoblast apoptosis and the corresponding mode of action. Methods: Transmission electron microscopy (TEM), assessment of DNA laddering, and flow cytometry assays were used to investigate human osteoblast apoptosis following infection with S. aureus. Results: TEM examination and DNA laddering assessment indicated that S. aureus can induce cultured human osteoblast apoptosis. Flow cytometry assays showed that human osteoblast apoptosis occurs in a dose‐dependent manner following infection with S. aureus. In addition, compared with under co‐culture conditions, inhibition of invasion by S. aureus resulted in a 64.62% reduction in the percentage of early apoptotic cells (P < 0.01); 7.09% ± 1.21% of human osteoblasts under indirect co‐culture with S. aureus at a multiplicity of infection of 250 showed an early apoptotic profile compared with uninfected controls(P < 0.01). Conclusions: S. aureus induces cultured human osteoblast apoptosis in a dose‐dependent manner. Intracellular S. aureus is mainly responsible for cultured human osteoblast apoptosis following infection; secreted soluble factor(s) of S. aureus playing a minor role in this process.     

Remote pharmacological post-conditioning by intrathecal morphine: cardiac protection from spinal opioid receptor activation

Background: Intrathecal morphine pre‐conditioning attenuates cardiac ischemia–reperfusion injury via activation of central opioid receptors. We hypothesized that intrathecal morphine also post‐conditions the myocardium in the rat. Methods: Intrathecal morphine at 0.3 μg/kg (LMPC), 3 μg/kg (MMPC) or 30 μg/kg (HMPC) was administered for 5 min before 120‐min reperfusion following 30‐min ischemia. Infarct size as a percentage of area at risk (IS/AAR) was determined using triphenyltetrazolium staining. MMPC was repeated following the intrathecal administration of nor BNI, NTD, CTOP, or naloxone methiodide (NM), kappa, delta, mu and non‐specific opioid receptor antagonists, respectively. The role of peripheral opioid, adenosine and calcitonin gene‐related peptide (CGRP) receptors was examined by the intravenous administration of NM, 8‐ρ‐sulfophenyl theophylline (8‐SPT) and human CGRP fragment (CGRP_8?37), respectively. Results: Morphine post‐conditioning at all three doses was cardioprotective (IS/AAR of LMPC=37±4%, MMPC=35±5%, HMPC=32±4%, control=50±5%, P<0.01). The prior administration of opioid receptor antagonists intrathecally, as well as intravenous 8‐SPT and CGRP_8?37 receptor antagonists, abolished this effect (nor BNI+MMPC=47±7%, NTD+MMPC=49±7%, CTOP+MMPC=45±9%, NM+MMPC=47±6% 8‐SPT+MPC=46±5% & CGRP_8?37+MPC=53±6%, P=0.63). However, the intravenous administration of NM did not prevent the protective effect (34±4%, P<0.01). Conclusions: Intrathecal morphine administration can induce pharmacological cardiac post‐conditioning as it involves opioid receptor centrally but non‐opioid receptors peripherally.     

Enhanced Selection of Candidates for Same-Day and Outpatient Total Knee Arthroplasty

BackgroundMedicare removed total knee arthroplasty (TKA) from its inpatient-only list and private insurers created ambulatory surgical codes; these changes bring about logistical challenges for TKA episode planning. We identified preoperatively determined factors associated with hospital length of stay for (1) same-day discharge (SDD) and (2) inpatient TKA defined by Medicare’s 2-midnight rule benchmark.MethodsWe retrospectively reviewed 325 consecutive unilateral primary TKAs performed on patients completing the Perioperative Surgical Home preoperative optimization pathway within a single hospital system. Stepwise logistic regression modeling was performed to identify preoperatively determined factors associated with (1) SDD and (2) inpatient TKA. We compared these models’ ability to discern the length of stay category to the Risk Assessment and Prediction Tool (RAPT) score alone.ResultsThe cohort included 32 (10%) SDD, 189 (58%) next-day discharges, and 104 (32%) inpatients. Lower body mass index (BMI; odds ratio [OR], 0.92; 95% CI, 0.85-0.1.0; P = .04) and fewer self-reported allergies (OR, 0.66; 95% CI, 0.46-0.95; P = .03) were associated with SDD. The SDD model outperformed the RAPT alone (C-statistic, 0.73 vs 0.52; P < .01). Older age (OR, 0.96; P = .04), higher BMI (OR, 0.93; P 0.01), lower RAPT score (OR, 1.2; P = .04), and later surgery start time (OR, 0.80; P < .01) were associated with inpatient discharge. The inpatient model outperformed the RAPT alone (C-statistic, 0.74 vs 0.62; P < .01).ConclusionWe identified preoperatively determined factors associated with (1) SDD as BMI and allergies and (2) inpatient TKA as age, BMI, RAPT score, and surgery start time. Hospitals, providers, patients, families, and payers can use this information for TKA episode planning.