Regenerative potential of mesoporous silica nanoparticles scaffold on dental pulp and root maturation in immature dog's teeth: a histologic and radiographic study.

OBJECTIVE: To evaluate histologically and radiographically the potential of dog's immature roots with apical periodontitis to regenerate after regenerative endodontic treatment using mesoporous silica nanoparticles (MSNs) with/without bone morphogenic protein (BMP-2) as scaffolds. METHODS: In 4 mongrel dogs, 56 immature teeth with 96 roots were infected, resulting in necrotic pulps and periapical pathosis. According to the evaluation time (Group I = 30 days and Group II = 90 days), 90 roots were divided into two equal groups (45 roots each) and 6 roots used to replace any lost root during the procedure. The two main groups were further divided according to treatment protocol into 5 subgroups (9 roots each): blood clot (BC subgroup), mesoporous silica nanoparticles scaffold only (MSNs subgroup), mesoporous silica nanoparticles impregnated with BMP2 (MSNs + BMP2 subgroup), infected teeth without treatment (+ ve control subgroup) and normal untouched teeth (-ve control subgroup). All teeth surfaces were coated with Tincture iodine and calcium hydroxide was applied prior to treatment protocols. Then, teeth were restored with glass ionomer filling to seal the remaining part of the access cavity. Radiography evaluation of the increase in root length, root thickness and occurrence of apical closure were performed. Following the sacrifice of the two dogs at each time of evaluation, histopathological analysis was performed and included the inflammatory cells count, bone resorption, tissue ingrowth, deposition of hard tissue, and closure of the apical part. All data were statistically analyzed. RESULTS: Compared to BC subgroup, MSNs and MSNs + BMP-2 subgroups exhibited significant higher increase in root length and thickness as well as higher vital tissue in-growth and new hard tissue formation in group II (P < 0.05). MSNs + BMP-2 subgroup had significant higher increase in root length and thickness as well as significant lower inflammatory cell count than MSNs subgroup in both groups (P < 0.05). There were no significant differences between MSNs and MSNs + BMP-2 subgroups regarding new hard tissue formation in both groups and apical closure in group I (P > 0.05). CONCLUSION: MSNs with/without BMP-2 scaffolds enabled the continuing growth of roots in immature teeth with necrotic pulps and periapical pathosis. Addition of BMP-2 to MSNs scaffold improved its outcome in regenerative endodontics. CLINICAL RELEVANCE: MSNs with/without BMP-2 scaffolds may alternate blood clot for regenerative endodontic treatment of immature teeth with necrotic pulps.

Leflunomide-induced cardiac injury in adult male mice and bioinformatic approach identifying Nrf2/NF-κb signaling interplay.

Leflunomide (LFND) is an immunosuppressive and immunomodulatory disease-modifying antirheumatic drug (DMARD) that was approved for treating rheumatoid arthritis. LFND-induced cardiotoxicity was not fully investigated since its approval. We investigated the cardiac injury in male mice and identified the role of nuclear factor erythroid 2-related factor 2/nuclear factor-κ B (Nrf2/NF-κB) signaling. Male albino mice were assigned into five groups as control, vehicle, and LFND (2.5, 5, and 10 mg/kg). We investigated cardiac enzymes, histopathology, and the mRNA expression of Nrf2, NF-κB, BAX, and tumor necrosis factor-α (TNF-α). The bioinformatic study identified the interaction between LFND and Nrf2/NF-κB signaling; this was confirmed by amelioration in mRNA expression (0.5- to 0.34-fold decrease in Nrf2 and 2.6- to 4.61-fold increases in NF-κB genes) and increased (1.76- and 2.625-fold) serum creatine kinase (CK) and 1.38- and 2.33-fold increases in creatine kinase-MB (CK-MB). Histopathological results confirmed the dose-dependent effects of LFND on cardiac muscle structure in the form of cytoplasmic, nuclear, and vascular changes in addition to increased collagen deposits and apoptosis which were increased compared to controls especially with LFND 10 mg/kg. The current study elicits the dose-dependent cardiac injury induced by LFND administration and highlights, for the first time, dysregulation in Nrf2/NF-κB signaling.

Comparing the Efficacy of Local Corticosteroid Injection, Platelet-Rich Plasma, and Extracorporeal Shockwave Therapy in the Treatment of Pes Anserine Bursitis: A Prospective, Randomized, Comparative Study.

Background: Pes anserine bursitis (PAB) is one of the most common causes of painful knee syndromes. This study aimed at examining the efficacy of local corticosteroid injection, platelet-rich plasma (PRP) injection, and extracorporeal shock wave therapy (ESWT) as different modalities to alleviate pain and enhance function in patients with pes anserine bursitis (PAB). Methods: A prospective, randomized, comparative study was conducted on 180 patients diagnosed with chronic PAB. They were equally divided into three groups as follows: Group I received a local corticosteroid injection of 40 mg of methylprednisolone acetate/1 ml; Group II received a PRP injection; and in Group III, ESWT was used. Outcome measures included the visual analog scale (VAS), Western Ontario and McMaster Universities (WOMAC) pain score, WOMAC physical function score, and Ritchie articular index (RAI) for tenderness, which were recorded at the baseline, after 1 week, and after 8 weeks. Results: Before the application of procedures, there was a statistically significant increase in the WOMAC pain score in the local corticosteroid group compared to the PRP group and the ESWT group (P < 0.001). After the application of procedures, there was a statistically significant improvement in the 1-week and 8-week WOMAC pain score, WOMAC physical function score, and VAS in the local corticosteroid group in comparison to the PRP group and the ESWT group. (P < 0.001). Moreover, RAI for tenderness shows statistically significant improvement at 8 weeks in the local corticosteroid groups compared to the PRP groups (P < 0.001) and ESWT groups (P < 0.001). Similarly, a statistically significant difference was found between the PRP and ESWT groups (P=0.023). Conclusion: Our data suggest that in patients with PAB, local corticosteroid injection is more efficient than PRP injection and ESWT for reducing pain and enhancing function.

Non-alcoholic fatty liver disease is associated with decreased bone mineral density in upper Egyptian patients.

Nonalcoholic fatty liver disease (NAFLD) has been linked with a number of extra hepatic diseases and could be a potential risk factor of decreasing bone mineral density. To determine whether Upper Egyptian patients with NAFLD are at risk of developing osteoporosis. Cross sectional study was done on a total 100 individuals; 50 patients diagnosed with NAFLD (based on ultrasound imaging) crossed-matched with 50 individuals without NAFLD based on age, sex and body mass index. Bone mineral density, serum calcium and phosphorus levels, serum parathyroid hormone, serum vitamin D and fasting insulin level were assessed. Osteoporosis was prevalent in NAFLD patients versus to controls (19/50 vs. 0/50; P < 0.001). There was significant decrease in bone mineral density in NAFLD patients than controls (- 2.29 ± 0.4 vs. - 1.53 ± 0.1; P < 0.001). There was a statistical significance decrease in serum vitamin D and calcium levels in NAFLD patients than controls. Furthermore, vitamin D levels in the NAFLD group was a predictor for osteoporosis (OR 0.614; 95% CI 0.348-0.825). Patients with NAFLD tend to have a significant decrease in bone density, vitamin D, and serum calcium levels than controls.

Silent Lupus Nephritis: Renal Histopathological Profile and Early Detection with Urinary Monocyte Chemotactic Protein 1.

Objective: Lupus nephritis (LN) affects almost half of all individuals with systemic lupus erythematosus (SLE). Overt LN (OLN) symptoms might vary from asymptomatic microscopic hematuria to renal failure. However, when there are no clinical or laboratory indicators of renal involvement, some people with silent LN (SLN) may have pathological evidence of renal involvement identified by renal biopsy. Monocyte Chemotactic Protein 1 (MCP-1) is a chemotactic factor that promotes leukocyte migration to the kidney. MCP-1 urine levels (uMCP-1) have been demonstrated to be high in individuals with active LN. The purpose of this study was to discover the occurrence of SLN, as well as the possible variations between overt LN (OLN) and SLN across SLE patients based on the histopathological assessment, as well as the role of uMCP-1 in the early detection of SLN. Methods: An overall of 144 patients with SLE were included in the current research. Patients were subsequently divided into two groups: individuals who did not have clinical evidence of LN (84 patients) and those with OLN (60 patients). All the patients were subjected to the following investigations: uMCP-1, erythrocyte sedimentation rate (ESR), complement C3 (C3), complement C4 (C4), creatinine, albumin/creatinine ratio (uACR), creatinine clearance, quantitative assessment of proteinuria by 24-hour urine proteinuria (24hr UP) and percutaneous renal biopsy. Results: Sixty patients from group I (71.4%) showed glomerular lesions on renal biopsy (SLN), and class II was the predominant class. uMCP-1 had a sensitivity of 95.2% and a specificity of 98% in the detection of SLN, and uMCP-1 values were markedly higher in patients with OLN in comparison to SLN. Conclusion: The actual frequency of SLN may be higher than expected. High levels of uMCP-1 may have warranted the early activity of LN. uMCP-1 can be used as a non-invasive, useful tool for the prediction of LN.

Evaluating Gender Differences in Egyptian Fibromyalgia Patients Using the 1990, 2011, and 2016 ACR Criteria.

Background: Fibromyalgia (FM) is a common rheumatic illness distinguished by chronic pain, fatigue, cognitive problems, and functional disability. However, the differences between men and women have not yet been comprehensively studied, especially after the development of the last 2016 American College of Rheumatology (ACR) criteria. The aim of this study was to evaluate the gender differences in symptom characteristics, cognitive dysfunction, and disease severity in Egyptian FM patients considering both the ACR 1990, 2011, and the last 2016 ACR diagnostic criteria. Methods: This is a prospective cross-sectional study that was carried out on 352 patients with FM in the Rheumatology Department, Al-Azhar University Hospital in Egypt, in the period between January 1, 2020, and June 1, 2021. In addition to the number of tender points (TPC), data was collected on age, gender, body mass index (BMI), marital status, disease onset, duration, and diagnostic delay. The widespread pain index (WPI), the symptom severity scale (SSS), fatigue, cognitive dysfunction, sleep disturbance, awakening unrefreshed, headache, abdominal pain, and depression were evaluated and scored according to 2010 and 2016 ACR criteria. A visual analog scale (VAS) for pain, fatigue, stiffness, anxiety, and depression is included in the questionnaire. The total score ranges were produced using total score ranges ranging from 0 to 80 (excluding job items), with higher scores indicating a stronger negative effect and/or intensity of symptoms. The polysymptomatic distress scale (PDS) has been calculated by the summation of the SSS with the WPI. The Revised FM impact questionnaire (FIQR) has also been evaluated. Results: The study shows that females have a significantly higher prevalence of fatigue, cognitive dysfunction, sleep disturbance, headache, and abdominal pain (p < 0.05). Also, females showed significantly higher scores than males regarding WPI, SSS, and mean TPC (p = 0.004, 0.027, and 0.001, respectively). While there was no difference regarding the FIQR (p=0.93), PDS was significantly higher in women (p= 0.001). Conclusion: Female patients with FM had greater disease severity scores, symptomatology, and number of tender points. Whatever the criteria applied, the prevalence and intensity of the disease features are higher in females, which may underestimate the disease in male patients.

Macrophage activation syndrome triggered by systemic lupus erythematosus flare: successful treatment with a combination of dexamethasone sodium phosphate, intravenous immunoglobulin, and cyclosporine: a case report.

BACKGROUND: Macrophage activation syndrome is classified as a secondary form of hemophagocytic lymphohistiocytosis. It is a hyperinflammatory complication observed to be comorbid with a variety of autoimmune diseases, including adult-onset Still's disease and systemic juvenile idiopathic arthritis. Macrophage activation syndrome is less commonly detected in adult patients with systemic lupus erythematosus, which, if untreated, can be fatal, though determining the optimum treatment strategy is still a challenge. CASE PRESENTATION: Herein, we report a case of macrophage activation syndrome in a 33-year-old Egyptian female as an unusual complication of a systemic lupus erythematosus flare in adult patients. Our patient was initially treated with a combination of intravenous methylprednisolone pulse therapy and intravenous immunoglobulin therapy, which was followed by a course of oral prednisolone and oral cyclosporine with little response. Switching from oral prednisone to intravenous dexamethasone sodium phosphate showed a more favorable clinical and biochemical response. CONCLUSION: Macrophage activation syndrome is less commonly detected in adult patients with systemic lupus erythematosus. Our case demonstrates that dexamethasone sodium phosphate can be a successful alternative treatment for patients with systemic lupus erythematosus complicated by macrophage activation syndrome in whom the response to pulse methylprednisolone was inadequate to manage their illness, proving to be remarkably effective in a relatively short time frame.

Supplement With Calcium or Alendronate Suppresses Osteopenia Due to Long Term Rabeprazole Treatment in Female Mice: Influence on Bone TRAP and Osteopontin Levels.

BACKGROUND AND PURPOSE: Rabeprazole, a proton pump inhibitor (PPIs) is much endorsed to patients with increased gastric acidity. PPIs were accused to have osteoporotic effects on patients who chronically use them. The point of the current investigation was to decide the impact of rabeprazole on osteoporosis and to explore the modulatory effects of dietary calcium or alendronate on this side effect. METHODS: 80 female mice were alienated into four groups maintained for 18 weeks: [1] Vehicle group: given distilled water in 12 ml/kg, P.O. [2] Rabeprazole control group: given rabeprazole in a dose equals 10 mg/kg every 48 h, P.O. [3] Rabeprazole + calcium: given rabeprazole (10 mg/kg every 48 h) along with calcium supplement. [4] Rabeprazole + alendronate: given rabeprazole (10 mg/kg every 48 h) and alendronate (1 mg/kg per week, i.p.). Serum calcium, phosphorus and parathyroid hormone were measured. Both femurs were kept in paraformaldehyde, and then the right one was used for X-ray examination with analysis by Digora software and the left one for histopathological examination (H&E) and immunohistochemical stains for osteopontin and tartrate resistant acid phosphatase (TRAP). RESULTS: Calcium supplementation or administration of alendronate along with rabeprazole significantly restored the mean bone density as shown by X-ray analysis. Femurs from mice received rabeprazole showed widely separated, thin-walled bone trabeculae and increased number of osteoclasts. Calcium or alendronate with rabeprazole showed thick bone trabeculae without full recovery from rabeprazole induced damage. Adding calcium supplementation to rabeprazole did not affect the histological abnormalities related to osteoclasts meanwhile alendronate produced inactivation of osteoclasts. Both calcium and alendronate decreased the rabeprazole-induced increment in the femur osteopontin level. CONCLUSION: Calcium or alendronate can be recommended for female patients on PPI therapy who are at risk of osteopenia.

Comparative study of the in vivo toxicity and pathophysiology of envenomation by three medically important Egyptian snake venoms.

Snakebite envenomation is a serious medical problem in many developing tropical and subtropical countries. Envenomation is registered by the World Health Organization as a neglected tropical disease due to critical shortages in the production of antivenom. Envenomation causes more than 100,000 deaths annually. Snakebites result in several effects to include edema, blistering, hemorrhage, necrosis and respiratory paralysis. Antivenom is the preferred treatment for the systemic effects of snakebite envenomation, though these are often ineffective in neutralizing venom toxin-induced local tissue damage. To effectively treat snakebites, it is important to determine the lethal potency and pathophysiological effects induced by specific snake venoms. In the current study, we compared the lethality, and the hemorrhagic and dermonecrotic activities of venoms from three snakes in Egypt that are the primary causes of local tissue necrosis. Our data show that the intraperitoneal median lethal doses (LD50) for Cerastes cerastes, Echis carinatus and Naja nigricollis venoms are 0.946, 1.744 and 0.341 mg/kg mouse body weight, respectively. These results indicated that N. nigricollis venom is the most toxic and significantly accelerated the time of death compared to the other two venoms. However, no hematoma or associated edema appeared upon sub-plantar injection of N. nigricollis venom into the mice hind paw. Two hours following intradermal injection of C. cerastes and E. carinatus venoms, macroscopic analysis of the inner surface of mouse skin showed severe hemorrhagic lesions, whereas only insignificant hemorrhagic lesion appeared in mice injected with the highest dose of N. nigricollis venom. Furthermore, the minimum necrotic doses (MND) for the same venoms were 43.15, and 70.87 µg/mouse, or not observed in the case of N. nigricollis venom, respectively. These LD50 values and pathophysiological results can be used to guide development of antivenom against bites by these dangerous Egyptian snakes.

Spermaurin, an La1-like peptide from the venom of the scorpion Scorpio maurus palmatus, improves sperm motility and fertilization in different mammalian species.

STUDY QUESTION: Is it possible to identify original compounds that are able to enhance sperm motility from the venom of the scorpion Scorpio maurus palmatus? SUMMARY ANSWER: We identified a potent disulfide-rich peptide (DRP) of 73 amino acids that significantly improved the motility of fresh and frozen-thawed sperm in different mammalian species, including human, and improved fertilization outcome in mouse IVF experiments. WHAT IS KNOWN ALREADY: Any disturbance of sperm motility has a strong impact on fertilization and can lead to subfertility or infertility. Significant efforts have, therefore,  been made to identify pharmacological drugs that might improve sperm motility. Such compounds are particularly useful in azoospermia to improve testicular sperm extraction and in the domain of cryopreservation because the motility of frozen-thawed sperm is reduced. STUDY DESIGN, SIZE, DURATION: This was a basic science/medical research study aimed at identifying original compounds from a library of venoms able to enhance mammalian sperm motility, including human. We first identified in the venom of a scorpion S. m. palmatus a fraction able to potently activate sperm motility. We next purified and characterized the compound by liquid chromatography, mass spectrometry and peptide synthesis. Finally, the potency and toxicity of both purified and synthetic versions of the identified compound on sperm motility were assessed using different in vitro tests in different mammalian species. PARTICIPANTS/MATERIALS, SETTING, METHODS: For human sperm, biological samples were collected from normozoospermic donors and subfertile patients attending a reproduction department for diagnostic semen analysis. Testicular sperm was collected from cynomolgus monkeys (Macaca fascicularis) euthanized for the needs of specific authorized research projects. The peptide was also tested on bovine and mouse epidydimal sperm. We measured different sperm motility parameters with a computer-assisted sperm analysis system in the presence or absence of the peptide. MAIN RESULTS AND THE ROLE OF CHANCE: Size exclusion chromatography enabled us to isolate a fraction of the venom of S. m. palmatus able to increase sperm motility. By liquid chromatography and mass spectrometry, a peptide comprising 73 amino acids with 4 disulfide bridges was identified as responsible for the biological activity and called 'spermaurin'. The identity of spermaurin was confirmed by chemical synthesis. We showed that the peptide increased the motility of fresh and frozen-thawed human sperm. We observed that the potency of the peptide was higher on fresh ejaculated spermatozoa with a low motility, achieving a 100% increase of curvilinear velocity in poorly performing sperm. We also demonstrated that peptide is effective on bovine and mouse fresh epididymal, bovine frozen-thawed ejaculated and fresh non-human primate testicular sperm. Finally, in mouse IVF, the production of 2-cell embryos was increased by 24% when sperm were treated with the peptide. LIMITATIONS, REASONS FOR CAUTION: This work is an in vitro evaluation of the ability of spermaurin to improve sperm motility parameters. Another limitation of this study is the small number of human sperm samples tested with the natural (n = 36) and synthetic (n = 12) peptides. Moreover, the effect of the peptide on IVF outcome was only tested in mouse and further tests with human and bovine gametes are required to confirm and extend this result in other mammalian species. WIDER IMPLICATIONS OF THE FINDINGS: This work confirms our initial study showing that venoms represent an interesting source of molecules that are able to modify sperm physiology. Moreover, this work presents the first demonstrated biological action of a venom peptide from the scorpion S. m. palmatus with sequence similarities to La1 peptide from Liocheles australasiae (Wood scorpion), a widespread family of DRPs. LARGE SCALE DATA: Not applicable. STUDY FUNDING/COMPETING INTEREST(S): This work is part of the project 'LAB COM-14 LAB7 0004 01-LIPAV', funded by the program LabCom 2014 from the French Research Agency (ANR). Dr Arnoult reports grants from IMV Technologies during the conduct of the study. In addition, Drs Arnoult, Martinez, Ray and Schmitt have a patent EP16305642.7 pending containing some of the information presented in this manuscript.

Push-out bond strength of fiber posts to root canal dentin using a one-step self-etching adhesive: the effect of solvent removal and light-curing methods.

PURPOSE: To evaluate the effect of solvent removal and light-curing methods on the push-out bond strength of fiber posts to root canal dentin using a one-step self-etching adhesive. MATERIALS AND METHODS: Eighty single-rooted, single-canal human mandibular premolars were used in this study. After removal of the crown, the pulp was extirpated and the post space was prepared. The teeth were divided into two main groups according to the solvent removal method, either using the paper point or the air-drying method. Each of the above main groups was further subdivided into 4 subgroups according to the light-curing method: group 1: both adhesive and resin cement were cured from the top of the post in the same step (cocuring) for 40 s; group 2: the adhesive was light cured for 20 s and the resin cement for 40 s; group 3: the adhesive was light cured for 40 s as was the resin cement; group 4: an intracanal tip was used to cure the adhesive inside the post space for 20 s. In groups 1 to 4, the solvent was evaporated using oil-free compressed air for 5 s from the root surface and excess adhesive was removed from inside the canal using a paper point. In groups 5 to 8, the adhesive and cement were applied and light cured as in groups 1 to 4, except the solvent was evaporated (air dried) from inside the post space using an intra-canal disposable plastic tip attached to the tip of a 3-way syringe. After 24 hours, three 2-mm-thick root slices were obtained from each root. Each slice was subjected to the push-out bond strength test at a crosshead speed of 0.5 mm/min. Factorial analysis (two-way ANOVA) was run to test the effect of solvent evaporation method, light-curing method, and their interactions on bond strength. One-way ANOVA followed by Duncan's Multiple Range Test were used to test the effect of lightcuring method on bond strength within each solvent evaporation method. Student's t-test was performed to compare the effect of solvent evaporation method on bond strength within each light-curing method. RESULTS: Two-way ANOVA revealed that the solvent removal method had a significant effect on the bond strength of fiber post to root canal dentin. Neither the light-curing method nor the interaction between the two independent variables had a significant effect on the push-out bond strength. CONCLUSIONS: Only air drying the one-step self-etching adhesive could influence the bond strength of the fiber post to root canal dentin.

Transforming growth factor beta and diastolic left ventricular dysfunction after heart transplantation: echocardiographic and histologic evidence.

BACKGROUND: The mechanism for chronic left ventricular diastolic dysfunction in the non-rejecting cardiac allograft has not been fully studied. OBJECTIVES: The purposes of this study were to analyze the significance and frequency of left ventricular diastolic dysfunction after heart transplantation and to examine the involvement of fibrotic cytokines (transforming growth factor beta [TGF-beta]) in development of clinical and echocardiographic changes in cardiac allograft recipients. METHODS: We studied 152 heart transplant recipients who had survived for at least 24 months. We compared histopathologic findings (staining of endomyocardial biopsy specimens using hematoxylin and eosin, and polyclonal antibodies expressed as TGF-beta score), left ventricular function (Doppler echocardiography), and clinical course (New York Heart Association [NYHA] status). We classified patients into Group 1 (n = 41 recipients) with a restrictive filling pattern, mitral deceleration time (MDT) <140 milliseconds, and Group 2 (n = 111 recipients), MDT >or=140 milliseconds. RESULTS: The MDT was 122 +/- 7 milliseconds in Group 1 compared with an MDT of 177 +/- 17 milliseconds in Group 2 (p = 0.0003). Group 1 showed significant immunohistochemical staining in endomyocardial biopsy specimens (a mean TGF-beta score of 9.1 +/- 1.2 for Group 1 compared with a mean TGF-beta score of 3.6 +/- 0.8 for Group 2 p = 0.001). The TGF-beta expression correlated inversely with both MDT and isovolumic relaxation time (r = -0.77, p = 0.0004, and r = -0.69, p = 0.004, respectively). Mean NYHA status in Group 1 recipients was 2.2 +/- 1.1 compared with 1.37 +/- 0.6 for Group 2 (p = 0.006). CONCLUSIONS: Transforming growth factor beta expression in cardiac allografts is associated with impaired left ventricular diastolic function. The pathogenesis of diastolic dysfunction may be an aberrant repair process after rejection-caused TGF-beta expression in the allograft.

Perfadex for clinical lung procurement: is it an advance?

BACKGROUND: Extensive laboratory experience suggested that low potassium dextran lung preservation solution (Perfadex; Medisan, Uppsala, Sweden) is superior to Euro-Collins (EC; Frusen, Hamburg, Germany), the clinical standard. The purpose of this study was to evaluate Perfadex in clinical lung transplantation. METHODS: A retrospective analysis of the outcome of 69 consecutive lung allografts retrieved and used for transplantation was made. Donor lungs were flushed with EC in 37 patients and Perfadex in 32 patients. The evaluation measurements were quantitative chest roentgenogram score (grade 0 to 4), graft oxygenation, duration of mechanical ventilation, length of intensive care treatment, and survival. RESULTS: The mean chest roentgenogram score was 1.55 and 1.81 for the EC group compared with 1.18 and 2.09 for the Perfadex group at 1 and 48 hours, respectively (p = 0.1 and 0.8, respectively). Arterial alveolar oxygen tension ratio was similar at 12 and 24 hours (0.61 vs 0.67; p = 0.8; and 0.64 vs 0.53; p = 0.3, respectively). The mean ventilation time was 71.2 +/- 32.3 hours versus 81.9 +/- 43.6 hours for the EC and Perfadex groups, respectively (p = 0.4). The mean intensive therapy unit stay was 3.1 +/- 2.6 days for the EC group compared with 4.1 +/- 3.9 days for the Perfadex group (p = 0.4). Death caused by primary organ failure was 5.1% for the EC group compared with 3.1% for the Perfadex group (p = 0.8). CONCLUSIONS: There was no difference between Perfadex and EC in clinical lung preservation. This may reflect the difference between controlled laboratory environment and the real world of brain death lung injury. Further studies are required to investigate the impact of Perfadex in the long-term outcome of lung transplantation.

Clinical significance of tricuspid valve dysfunction after orthotopic heart transplantation.

OBJECTIVES: Tricuspid regurgitation (TR) is common after heart transplantation (OHT), but its clinical relevance is undetermined. This study documents the clinical progress of patients with TR after OHT in relation to the severity of TR. METHODS: We studied 238 transplant recipients who had survived for at least 12 months after OHT. Tricuspid regurgitation was graded clinically and by assessing regurgitant jet area. Recipients were divided into those with no TR Group 1 (n = 64), those with sub-clinical TR (TR absent clinically and regurgitant jet area <25%, Group 2 (n = 89), and those with clinical TR (with clinical TR or regurgitant jet area > or =25%, Group 3 (n = 85). RESULTS: We found no significant difference among the groups in terms of age, or pre-operative events. At 12 months after OHT, mean right atrial and pulmonary artery pressures were higher in Group 3 than in Group 1 or Group 2 (p = 0.005 and 0.03, respectively). Right ventricular end-diastolic and end-systolic volumes were smaller for recipients in Groups 1 and 2 compared with those in Group 3 (p = 0.01 and 0.02). The annual development of renal impairment was 0.019 (95% confidence interval [CI], 0.014-0.029), 0.026 (95% CI, 0.022-0.62), and 0.613 (95% CI, 0.346-0.756) in Groups 1, 2, and 3, respectively (p = 0.02). At the most recent follow-up, mean New York Heart Association class for Group 1 was 1.4, for Group 2 was 1.7, and for Group 3 was 2.7 (p = 0.04). CONCLUSIONS: The integrity of the tricuspid valve has a significant impact on long-term clinical progress of OHT recipients. Recipients with significant TR are more symptomatic and have poorer right-sided heart function compared with those with mild or no TR.

Pulmonary vein gas analysis for assessing donor lung function.

BACKGROUND: Radial artery oxygenation (PaO2) is the standard method for assessing potential lung donors. This study was proposed to assess the use of pulmonary vein gases (PvO2) in selection of donor lung for transplantation. METHODS: We studied 170 lungs from 85 consecutive donors. Lungs were classified into group A, PaO2 and PvO2 > 300 mm Hg; group B, PaO2 < 300 mm Hg, and PvO2 > 300 mm Hg; and group C, PvO2 < 300 mm Hg. RESULTS: Lungs retrieved from group A and group B were used for transplantation. Allograft function, assessed by the arterial and alveolar oxygen tension ratio, was similar at 12 hours and at 24 hours after operation (0.69, 0.73, vs 0.70, 0.71, for groups A and B, respectively (p = 0.8, 0.7, respectively). Similar radiologic appearance was seen in both groups (p = 0.2). Median duration of intubation was also similar (p = 0.6). The 30-day mortality rate was 12% versus 11.3% (p = 0.8), and 1-year survival rate was 80% versus 82% (p = 0.8) for recipient received lungs from group A and B donors, respectively. CONCLUSIONS: Selective pulmonary veins analysis gives an accurate assessment of individual gas exchange in comparison with arterial PaO2, identifying more potential donor lungs for transplantation.

The management of second primary lung cancers. A single centre experience in 15 years.

OBJECTIVE: In patients treated for an initial lung cancer, the cumulative risk of developing a second primary lung cancer is a recognised occurrence. This study reviews our experience in the clinical assessment and surgical management of second primary lung cancer (SPLC). METHODS: Between 1985-1999 a series of 892 patients with primary carcinoma of lung underwent surgical resection with curative intent in our institution. Using criteria set out by Martini and Melamed (J Thorac Cardiovasc Surg 70 (1975) 606) we were able to identify 51 patients who had developed a SPLC identified as the first site of re-occurrence. RESULTS: Forty-one patients developed a metachronous SPLC within a mean of 46+/-14 months of the first operation while ten patients had synchronous double lung cancer (six unilateral, four bilateral). The cumulative probability of cancer free interval for metachronous cancers was 39% at 3 years, 15% at 5 years and 2% at 10 years. There were three postoperative deaths among the metachronous cancers (7.5%) and there were no operative deaths among patients with synchronous cancers. The overall actuarial 5-year survival for all patients with SPLC was 38% with a median survival of 40 months (range 1-142 months). The actuarial 5-year survival for metachronous SPLC was 44%, median survival of 49 months (range 1-142 months), while the actuarial 5-years survival for synchronous SLPC was 10% with a median survival of 31 months (range 4-78 months). CONCLUSION: Aggressive assessment and surgical intervention is safe, effective and warranted in patients with a second lung primary cancer if they satisfy the usual criteria of operability after full assessment. This is true for patients with metachronous cancers, while patients with synchronous cancers tend to have worse prognosis. A long term follow-up policy after the initial resection of the primary lung cancer is recommended at intervals of 6 months for at least 3-5 years and then annually to enable the early detection of the second cancer.