Başkent Üniversitesi Makaleler

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A Case of Falling Into an Acid Tank From Height After High-Voltage Electrocution
(Başkent Üniversitesi, 2024-12) Burak Özkan; Abdullah Kızmaz; Uğur Bak; Khalid Zeynalov; Süleyman Savran; Abbas Albayati; Çağrİ A. Uysal; Mehmet Haberal
In this case report, we present the management of a dramatic and rare combination of injuries: high-voltage electrical injury, chemical burn, and open tibial and calcaneal fractures resulting from a fall from height. The patient underwent early fasciotomies. After treatments administered by a multidisciplinary team consisting of plastic surgeons, general surgeons, orthopedic specialists, anesthesiologists, and physiotherapists, the patient was discharged without extremity loss after a 135-day hospital stay. This case report discusses the importance of early fasciotomy and debridement in management of extensive burns and fall-related injuries, the potential for extended hospitalization for reconstruction, and the necessity of a multidisciplinary approach.
A Case of Progressive Mortal Thrombosis: Phlegmasia Cerulea Dolens
(Başkent Üniversitesi, 2023-03) Khalid Zeynalov; Burak Ozkan; Tankut Akay; A. Cagri Uysal; Mehmet Haberal
ABSTRACT Phlegmasia cerulea dolens is a very rare set of conditions associated with acute, massive venous thromboembolism. Medical and surgical options can be combined in treatment. Patients may experience sudden onset and severe leg pain, edema, cyanosis, compartment syndrome, and post-venous gangrene amputation and death. Medical and surgical treatments can be combined in treatment. Anticoagulants, thrombectomy, percutaneous procedures and amputations are among the treatment options. We present a 60-year-old female patient with a diagnosis of diabetes mellitus with swelling, pain, and discoloration in the left lower extremity who died due to progressive venous thrombosis despite various treatment modalities. Wound debridement and thrombectomy were performed. On day 10 of hospitalization, the patient was intubated to treat resistant low saturation. Despite the interventions, the patient died on day 10 of hospitalization due to cardiopulmonary arrest. Early diagnosis and treatment are vitally important. As in the case we presented, sometimes patients die as a result of rapid clinical progression and side effects, despite the use of different medical and surgical treatments.
A Clinicoepidemiological and Outcome Analysis of 770 Burn Patients: A 5-Year Retrospective Study in a Private Sector Tertiary Burn Care Center in Indore, Central India
(Başkent Üniversitesi, 2022-09) Rajpal Singh; Shobha Chamania; Sunil Chandiwal; Deepak Tripathi; Deepika Jain; Ankit Mishra; Tasvir Balar; Prashant Srivastava
ABSTRACT OBJECTIVES: Burns are a global public health problem and one of the major causes of disability, with more than 8 million disability-adjusted life-years. Our aim was to contribute a comprehensive analyses of existing burn data from Central India. MATERIALS AND METHODS: We reviewed secondary data of burn patients from 5 years (March 2016 to March 2021) from a single center (Choithram Hospital & Research Centre, India). All burn patients except those with nonhealing and old burn wounds were included. We examined the following: age, sex, socioeconomic status, type of burn, total burn surface area, comorbidities, treatment, and outcome, with data analyzed using Statistical Package for Social Sciences version 20.0. RESULTS: Our study included 770 patients (median age of 28.0 y). Male-to-female ratio was 1.26:1. Burns were common in the reproductive age group of 21 to 40 years (48.6%) and in people of a lower socioeconomic status (65.2%). There was predominance of flame burns (82.0%). The most common mode of burning was accidental (79.4%). The median (interquartile range) of total burn surface area among patients was 25% (12%-45%). Flame burns resulted in significantly greater injury (total burn surface area 30.0%) compared with electric (total burn surface area 23.0%) and scald burns (total burn surface area 11.5%). The commonest comorbidities were hypertension (5.2%) and diabetes (4.7%). We observed significant associations between outcome and age, sex, comorbidities, and treatment modalities. Homograft, autograft, or collagen/other dressing or a combination of these compared with conservative treatment resulted in better healing and reduced hospital stay (P < .001). CONCLUSIONS: Age, sex, type of burn, total burn surface area, comorbidities, and treatment modalities were significantly associated with outcome of burn patients.
A Fast and Safe Living-Donor "Finger-Assisted" Nephrectomy Technique: Results of 225 Cases
(Başkent Üniversitesi, 2008-12) Hakim, Nadey S.; Canelo, Ruben; Papalois, Vassilios
Renal transplant remains the treatment of choice for end-stage renal disease. It improves both the quality of life and the quantity of life in recipients. We present a living-donor nephrectomy technique that is less invasive than the conventional open flank incision. This technique involves only 1 incision and is smaller than the one used in the laparoscopic technique. We have successfully introduced this new technique at our center. The procedure may be done safely and is applicable in all potential donors regardless of the body mass index of the donor or the size of the surgeon’s hands. It provides excellent grafts and has allowed us to expand our living-donor program.
A Monocentric Observational Study of Darbepoetin Alfa in Anemic Hepatitis-C-Virus Transplant Patients Treated With Ribavirin
(Başkent Üniversitesi, 2008-12) Kamar, Nassim; Rostaing, Lionel; Esposito, Laure; Ribes, David; Guitard, Joëlle
Objectives: Darbepoetin alfa is used to treat renal anemia; however, little information is available concerning its use during the posttransplant period, especially in HCV-positive patients treated with ribavirin for active hepatitis C. Materials and Methods: This study investigated the efficacy and safety of using darbepoetin alfa in this population during a 6-month treatment period. All anemic patients were HCV/RNA-positive, treated with ribavirin, and had impaired renal function. Patients (n=7) who had not been treated previously with recombinant human erythropoietin (rHuEPO) were placed in “group no rHuEPO.” Patients previously with recombinant human erythropoietin (n=16; “group rHuEPO”) were switched to darbepoetin alfa according to the European summary of product characteristics. Results: Seventy-three percent of the patients were men. The mean creatinine clearance at baseline was 58.7 ± 21.5 mL/min. All patients received an immunosuppressive treatment. Although mean hemoglobin levels remained stable in group no rHuEPO and increased in group rHuEPO, the difference was not statistically significant. Also, the median darbepoetin-alfa–weighted dose in group no rHuEPO increased while it remained stable in group rHuEPO, as did the median daily dosage of ribavirin; however, these differences were not statistically significant. Creatinine levels and creatinine clearance levels remained stable throughout the study. No significant medical events related to the treatment were reported during the study. Conclusions: Darbepoetin alfa was found to be efficient and well tolerated in correcting renal anemia in transplant recipients treated with ribavirin for active hepatitis C.
A New Method for Determining the Volume Of Blood Loss During Necrectomy in Patients With Deep Burns
(Başkent Üniversitesi, 2023-06) Evgenij V. Zinoviev; Denis O. Vagner; Alexander E. Chukharev
ABSTRACT OBJECTIVES: Most surgery manuals indicate that, for excisions of a burn scab on an area of 1 cm2 with skin plasty, blood loss, taking into account donor zones, is about 1 mL. This volume of alleged blood loss plays an essential role in planning surgical treatment of patients with burn injuries. To date, when volume of lost blood is calculated with the use of existing methods for determining intraoperative blood loss, it is not recommended to excise necrotic tissues on an area of more than 15% of the body surface. In this study, our aim was to develop a new formula for determining intraoperative blood loss during necrectomy in patients with deep burns. MATERIALS AND METHODS: We developed and proposed our own, original method for determining the volume of intraoperative blood loss, based on taking into account hemoglobin and hematocrit indicators, as well as differentiated calculation of the volume of circulating blood. This technique was tested on 109 patients with deep burns (per ICD-10), who were admitted to our department from January 2022 to December 2022 because of thermal lesions. We processed obtained data using Microsoft Office Excel and used generally accepted methods of nonparametric statistics. RESULTS: With the new formula, we determined blood loss of 0.52 mL per 1 cm2 of excised tissue, which is 2 times less than predicted by traditional methods. CONCLUSIONS: Our results showed that the expected intraoperative blood loss may not be 1 mL/1 cm2, as currently prescribed in clinical guidelines, but 0.5 mL/1 cm2 of the excised tissue. Our results allow for possible expansion of the removal of the burn eschar before the development of infectious complications.
A Novel Approach in Clinical Immunosuppression Monitoring: Drug Lymphocyte Level
(Başkent Üniversitesi, 2007-12) Barbari, Antoine; Masri, Marwan A.; Stephan, Antoine; Rizk, Sylvana; Younan, Farida
Like others, we have shown a weak correlation between drug blood levels and clinical outcome and immune response. We recently established that in contrast to blood levels, drug lymphocyte levels are strongly associated with therapeutic efficacy. The discordance between the 2 methodologies regarding clinical outcome and immune response is related mainly to the weak association between drug blood level and target-cell content. This weak association explains the intra- and interindividual variabilities of the therapeutic response. These variations are related mainly to genetic and environmental factors including age, sex, body mass index, organ function, food and subsequent drug absorption, drug interactions, and the availability of extra–target-cell binding sites. These factors seem to influence the modes of action of immunosuppressive agents including drug absorption, metabolism, elimination, transport, extra–target-cell sites, as well as target-cell receptor expression and its binding affinity and specific enzyme baseline activity. Therefore, the cellular fraction of a drug at a fixed dosage is the result of the integration of out-fluxing and in-fluxing forces that are affected by genetic and environmental factors. Any redistribution of the drug between the different binding sites will ultimately affect its bioactivity with no change to its extracellular bioavailability (which is currently determined by pharmacokinetic measurements). Compared with whole-blood or plasma-level measurements, monitoring immunosuppression therapy at the site of action appears to be not only more clinically and immunologically relevant (since it measures the free fraction of the drug at its effector site), but this method also bypasses the potentially complex extracellular factors that affect bioactivity. Since the intracellular content of a drug strongly correlates with its biological effect, monitoring immunosuppression therapy at the site of action is comparable to pharmacodynamic monitoring. It is cost effective and easy to perform in clinical practice and could be used for all immunosuppressive drugs. Since it allows maximal reduction of adverse effects through dosage reduction while maintaining an optimal level of immunosuppression, it should offer a new alternative for immunosuppressive therapy monitoring and tailoring to the individual patient.
A Novel Technique for Hepatic Arterial Reconstruction in Living-Donor Liver Transplant
(Başkent Üniversitesi, 2007-06) Haberal, Mehmet; Sevmis, Sinasi; Karakayali, Hamdi; Moray, Gokhan; Yilmaz, Ugur; Ozcay, Figen; Torgay, Adnan; Aydogan, Cem; Arslan, Gulnaz
Objectives: Arterial reconstruction in patients undergoing living-donor liver transplant is technically difficult because of the small diameter of the vessels in the partial liver graft. In this study, we present our technique for hepatic arterial reconstruction. Methods: Since December 2005, we have performed 54 living-donor liver transplants, which are analyzed retrospectively in this report. In our technique now used at our institution, native and graft hepatic arteries are spatulated from both the anterior and posterior walls to provide a wide anastomosis. Computed tomographic angiography is used to evaluate the vascular anatomy and to measure the diameter of the graft hepatic arteries. Results: Mean follow-up was 7.2 ± 5.5 months (range, 1-17 months). Nine of the 54 recipients died within 4 months of the surgery. At the time of this writing, the remaining 45 recipients (84%) are alive and demonstrating good graft function. In 2 recipients (3.7%) in this series, hepatic artery thromboses developed, which were treated with an interventional radiologic technique. Conclusions: Our arterial reconstruction technique has enabled reconstruction of smaller arteries and arteries of various diameters without an operating microscope. The rate of complications in our patients is similar to that reported in similar individuals.
A Rehabilitation Case Management Model for Severely Burned Victims
(Başkent Üniversitesi, 2022-12) Emilio Gonzalez Silva
ABSTRACT In Chile, since 2007, the treatment of people with major burns is protected by the Explicit Health Guarantees Law, which guarantees access, opportunity, and financing to public and private providers that offer treatment compliance and follow-up. This includes the Emergency Hospital of Public Assistance, located in Santiago, the main National Reference Center for the management of burns in adults throughout the national territory. To favor the counter-referral of severely burned patients after their care at the National Reference Center Emergency Hospital of Public Assistance, a follow-up process has been designed during all in-hospital rehabilitation phases. This has been named the Rehabilitation Case Management model, with the additional emergence of the rehabilitation case manager.
A Report of Outcomes After Orthotopic Liver Transplant With Allografts From Heparin Antibody-Positive Donors
(Başkent Üniversitesi, 2009-12) Aloia, Thomas A.; Goss, John A.
Heparin-induced thrombocytopenia (HIT) is an immune-mediated condition associated with thrombocytopenia and thrombotic complications. The condition is increasingly recognized in hospitalized patients including severely injured trauma patients. Because these patients may eventually be considered for organ donation, management of the HIT screen-positive donor has become an important issue in transplant surgery. We describe the recent management of 2 liver allograft donors with relative thrombocytopenia and positive HIT antibody screens. In both cases, systemic anticoagulation at the organ recovery operation was accomplished with argatroban, a synthetic thrombin inhibitor. This management strategy resulted in successful transplants for 7 recipients (1 heart, 2 liver, 4 kidney). Neither of the liver recipients demonstrated signs or symptoms of HIT, and neither had any postoperative thrombotic complications. Based on this experience, a treatment algorithm for managing HIT-positive donors is proposed. In addition, the pathophysiology of HIT and various testing modalities for the disorder are discussed.
A Retrospective Study of Conversion From Tacrolimus-based to Sirolimus-based Immunosuppression in Orthotopic Liver Transplant Recipients
(Başkent Üniversitesi, 2008-06) Yu, Si; Huang, Jiefu; Ju, Weiqiang; Zhu,Xiaofeng; Ma, Yi; Yang, Lu; He, Xiaoshun
Objectives: Calcineurin inhibitors are used widely in liver transplant recipients. Sirolimus is a new, potent immunosuppressant considered to be nonnephrotoxic. There is limited experience with the use of sirolimus in liver transplant recipients. This study aimed to investigate the clinical experience of conversion from tacrolimus-based to sirolimus-based immunosuppression in liver transplant recipients. Patients switched to cyclosporine-based immunosuppression during the same period were enrolled as controls. Materials and Methods: This retrospective study examined liver transplant recipients who had been switched from tacrolimus-based to sirolimus-based or cyclosporine-based immunosuppressive therapy between January 2004 and January 2007 in the first affiliated hospital of Sun Yat-sen University. Patients were divided into 3 groups: those switched to sirolimus-based immunosuppression owing to acute rejection (group SIR-AR; n=11); those switched to sirolimus-based immunosuppression owing to renal insufficiency (group SIR-RI; n=18), and those switched to cyclosporine-based immunosuppression owing to acute rejection (group CsA-AR; n=15) Results: In patients switched owing to acute rejection, the rate of successful conversion was 54.5% in group SIR-AR (6/11) compared with 60% in group CsA-AR (9/15); this difference was not statistically significant (P > .05). After conversion, renal function in patients in group SIR-AR remained normal. Conversely, renal function in patients in group CsA-AR became abnormal 3 months after conversion. In patients who were switched owing to renal insufficiency in group SIR-RI, renal function improved significantly after conversion (P < .05). In the sirolimus groups, some sirolimus-associated adverse effects occurred but were limited and well controlled. Conclusions: Sirolimus can be used safely in liver transplant recipients. In the early stages after liver transplant, sirolimus combination therapy is recommended to prevent acute rejection. For patients with tacrolimus-related adverse effects, a sirolimus-based immunosuppression regimen is a rescue therapy.
A Study on Employment in Non-Life Insurance Companies: Fuzzy Regression Example
(Başkent Üniversitesi, 2022-12-12) Akgül ,Yusuf; Çamlıbel,Fuat; Şengönül , Ahmet
Purpose: In this study, factors affecting employment in non - life insurance companies were examined. These factors are the financial variables of insurance companies, including financial profit-loss, total net premiums, total assets and technical profit-loss. Methodology: Fuzzy regression method was used as the solution method. Findings: According to the results, the change interval of the financial variables was found significant at h = 09. As a result, the change interval in total assets was % 0.0906, the financial profit was nearly “0”, technical profit/loss was % 0.0392 and the sum of premiums was % 62,04. Also, real employment data was found to be closer to the upper regression limit. Implications: The results obtained by the fuzzy regression method are quite better from the panel data solution method in terms of the consistency of the estimates. When it is desired to generate prediction models for the employment with financial variables of the companies in the sector, the fuzzy regression method is good at creating meaningful models and gives more consistent information about the coefficient of the related arguments. If the results of the study will be interpreted economically and socially; it was observed how internal variables, which are thought to affect the employment capacity of insurance companies, affect employment in insurance companies. It is observed that the increase in the size of premium gain in insurance companies has a positive effect on its employment. This effect will have positive effects on creating new employment in the insurance sector. This increase in employment will also have positive effects for the country's economy. Limitations: However, developing technology and making many insurance transactions online will cause companies to decrease their employment capacity even if their premium gain size increases. For example, there will be a decrease in needed field sales staff and number of agencies. In this case, on the contrary, it will increase the number of unemployed people in insurance sector and in the country. The decrease in employment and increasing unemployment will affect both people and the country's economy negatively. Economically, a negative outlook will occur in the domestic and foreign markets.
ABO Incompatible Kidney Transplantation -Immunological Aspect-
(Başkent Üniversitesi, 2003-12) Aikawa, Atsushi; Yamashita, Mioko; Hadano, Tomomi; Ohara, Takehiro; Arai, Kenji; Kawamura, Takeshi; Hasegawa, Akira
ABO incompatible kidney transplantation (ABOINCKT) has been developed in Japan because of the shortage of cadaveric donors. We have performed 76 living-donor ABOINCKT in our center. Donor blood type antibody was removed by immunoadsorption or plasmapheresis and exchange. Immunosuppression consisted of cyclosporine or tacrolimus, steroid, and cyclophosphamide or azathioprine or mycophenolate mofetil and, recently, basiliximab. Splenectomy was routinely performed during the transplantation surgery. Donor blood type antigen was strongly expressed on the vascular endothelium at all time points and in all conditions posttransplantation. Red blood cell agglutination reaction (RBAR) was positive only in renal tissues from a patient with delayed hyperacute rejection. Donor specific antibody suppression was observed in 18 ABOINCKT recipients with blood type O from a donor with blood type A1 or B. ADCC activity was detected after pre-treatment. Acute humoral rejection in ABOINCKT can result from ADCC, as well as by antigen-antibody reaction. Five year graft and patient survival rates were 75% and 64% in 37 ABOINCKT recipients from June 1989 through December 1996, however they have been 100% in 39 ABOINCKT recipients since January 1997. Accommodation has been produced in ABOINCKT with the co-existence of blood type antigen and antibody. Currently, ABOINCKT is an alternative which should be considered, particularly for blood type O patients with extended waits for cadaveric transplantation and for pediatric patients.
Acute Renal Failure in the First 100 Orthotopic Liver Transplant Patients in Southern Iran
(Başkent Üniversitesi, 2007-12) Rais-Jalali, Ghanbar-Ali; Malek-Hosseini, Seyed Ali; Salahi, Heshmatolah; Bahador, Ali; Nikeghbalian, Saman; Roozbeh, Jamshid; Behzadi, Saeed; Daniali, Farzad; Sagheb, Mohammad Mahdi
Postoperative acute renal failure is a frequent and serious medical complication following orthotopic liver transplant. Here, we report our experiences with liver transplant recipients who developed acute renal failure in the early period following orthotopic liver transplant. Among 100 liver transplants performed between April 1993 and January 2004, we retrospectively analyzed 91 patients (mean age, 29.9 ± 14.0 years) who had undergone orthotopic liver transplant. The underlying causes of liver failure were cryptogenic liver cirrhosis (n=27), viral hepatitis (n= 21) (hepatitis-B–related liver cirrhosis [n=13], hepatitis-C–related liver cirrhosis [n=7], and hepatitis-B– and C–related liver cirrhosis [n=1]), autoimmune hepatitis (n=18), Wilson’s disease (n=10), primary sclerosing cholangitis (n=8), biliary atresia (n=3), Budd-Chiari syndrome (n=2), and primary biliary cirrhosis (n=2). The immunosuppressive regimen included mycophenolate mofetil (azathioprine for 10 patients), cyclosporine, and steroids. Six patients received a combination of tacrolimus and steroids. Ten patients (10.9%) experienced acute renal failure, 7 (70%) were men, and none of them required renal replacement therapy and/or died. Four patients were diagnosed as having cryptogenic liver cirrhosis; 2 with hepatitis-C–related liver cirrhosis, 2 with autoimmune liver cirrhosis; 1 with primary biliary cirrhosis; and 1 hepatitis-B–related liver cirrhosis. Six patients were Child-Pugh's classification C, and the others were B. The rate of postoperative acute renal failure in our patients was relatively low when compared with other series, and our outcomes were good.
Acute Tubular Necrosis After Renal Allograft Segmental Infarction: The Nephrotoxicity of Necrotic Material
(Başkent Üniversitesi, 2008-12) Ardalan, Mohammad Reza; Shoja, Mohammadali Mohajel; Ghabili, Kamyar; Nasri, Hamid
Objectives: Renal allograft dysfunction can be caused by renal vessel thrombosis, acute tubular necrosis, hyperacute or acute rejection, nephrotoxicity induced by cyclosporine or tacrolimus, thrombotic microangiopathy, or urinary tract obstruction. Materials and Methods: We describe a renal transplant recipient in whom oliguria developed during the first week after transplant, although his early renal allograft function was good. Results: A Doppler ultrasonographic study revealed a lack of perfusion in the lower pole of the allograft. A perfusion defect was noted in the lower pole that was supplied by a polar artery, which had been damaged during engraftment. Light microscopy disclosed tubular cell necrosis without evidence of vascular or humoral rejection. Conclusions: We suggest that toxic molecules such as tumor necrosis factor-alpha released from a segmental infarcted area can induce tubular cell damage and necrosis leading to renal allograft dysfunction.
Advances in the Development of Tissue Engineering Applied to the Skin Using Three-Dimensional Bioprinters for the Treatment of Burn Patients
(Başkent Üniversitesi, 2021-06) Alberto Bolgiani; Elida Hermida; Priscilla Alcocer; Giovanni Alcocer
The concept of three-dimensional printing was developed in 1980, and the idea of three-dimensional printing to manufacture objects was established in 1986. In 1993, the technology allowed the printing of plastics and metals, with a series of three-dimensional printers having different applications being subsequently developed. In 2002, Italian researchers developed the dermal regeneration matrix (hyalomatrix) with hyaluronic acid and silastic fibers, mimicking the epidermis. In 2003, Mexican researchers developed an allogeneic keratinocyte culture as a system for the release of growth factors in skin lesions. Over the past 10 years, 15 matrices of dermal regeneration have been developed. This technology has had a great impact on engineering and medicine. In medicine, an important application is tissue engineering, not only for the manufacturing of skin and grafting but also for conducting scientific investigations on the evaluation and discovery of drugs. The use of bioprinting of tissues can allow a layer-by-layer aggregation of cells to be obtained, allowing organization of multiple cell types in a desired structure. After in vitro cell culture, allowing respective growth and maturation to achieve the desired tissue, tissue implantation can then be performed. The three-dimensional bioprinting technique can improve both spatial resolution and reproducibility, allowing optimal conditions for cell incubation and maturation. In addition, with a limited supply of donors, bio-fabrication of organs and tissues can help with future transplant procedures.
Age and Donor Safety in Living-Donor Liver Transplant in 110 Consecutive Cases at 1 Institute
(Başkent Üniversitesi, 2008-09) Ishiko, Takatoshi; Baba, Hideo; Takeitchi, Takayuki; Okajima, Hideaki; Asonuma, Katuhiko; Beppu, Toru; Inomata,Yukihiro
Objectives: Since Japan began doing living-donor liver transplants, the demographics of living donors, including their age, have changed. We sought to assess the impact of aging on the feasibility and safety of doing a hepatectomy in living donors. Materials and Methods: We analyzed data from 110 consecutive liver donors who had undergone a hepatectomy at our institution. To extract the graft, 34 patients had a lateral segmentectomy, 38 had a left lobectomy, and 38 had a right lobectomy. Results: Mean intraoperative blood loss was significantly greater in older donors (age > 40 years) than it was in younger donors (age ≤ 40 years). In addition, the mean number of days required for the serum albumin level to return to normal after surgery was significantly longer in older donors (34.3 ± 11.9 days vs 17.1 ± 9.7 days). A multivariate analysis showed donor age to be a significant risk factor for prolonged serum albumin recovery. Conclusions: Donor age is a significant factor affecting postoperative liver functioning in the donor.
Ageing and Immunosuppression in Kidney Transplantation
(Başkent Üniversitesi, 2004-12) Land, Walter Gottlieb
Modern approaches to tailor-made, individualized immunosuppressive therapy for patients receiving organ transplantation require a rethinking of therapeutic strategies when it comes to older persons receiving kidney transplants, especially from deceased older donors. This review article makes the case for the use of calcineurin-inhibitor–free immunosuppressive induction/maintenance protocols in this “worst-case scenario” and discusses the theoretical and clinical data that support this recommendation. We will discuss modern theories of ageing, emphasizing the free-radical theory in relation to new insights into the mechanisms of innate immunity. In this context, a new, modified theory of ageing is presented. Increased generation of reactive oxygen species during ageing, via increased leakage of these oxidizing molecules from mitochondria, may contribute to senescence and age-related diseases by direct damage to intracellular DNA, proteins, and lipids. In addition, free-radical–mediated tissue injury, accompanied by induction of damage-associated molecular patterns, may result in activation of both inflammatory and vascular cells of the innate immune system, contributing (via inflammatory processes) to ageing and age-related diseases such as atherosclerosis. Calcineurin-inhibiting agents have been shown to induce oxidative stress and are thus defined as “proageing” drugs. Their use in older patients may aggravate the preexisting oxidized intracellular state and therefore should be avoided. In contrast, inosine-monophosphate dehydrogenase–inhibiting agents such as mycophenolate mofetil have been shown to even ameliorate oxidative stress and are thus defined as “antiageing” drugs. Therefore, their use for immunosuppression in older patients receiving kidney transplantation is suggested. This recommendation is supported by data from a prospective trial on the application of a calcineurin-inhibitor–free, mycophenolate-mofetil–based indu-ction/maintenance immunosuppressive protocol in older recipients of kidneys from deceased older donors: the 5-year patient and 5-year allograft survival rates are currently 87% and 70%, respectively.
Allograft En Bloc Vagino-Utero-Ovarian Avascular Transplant Versus Autograft Implantation in Rats
(Başkent Üniversitesi, 2008-12) Eghtesadi-Araghi, Payam; Moghimi, Mehrdad; Salehian, Mohammad-Taghi; Salehian, Arash; Mossaffa, Nariman; Hadian, Mehrnaz
Objectives: The aim of this study was to compare the results of an allograft en bloc vagino-utero-ovarian avascular transplant with those of autograft implantation in rats. Materials and Methods: Thirty-four inbred adult virgin female Albino rats (age range, 10 - 12 weeks) were divided into 2 groups: the control group (autograft, n=11) and the study group (en bloc vagino-utero-ovariectomy, n=23). In the study group, the uterus and adnexa and the ovaries of the donor rat were transplanted to the recipient animal. Twenty-five to 30 days after that procedure, all rats were killed, and the samples were assessed histopathologically. No immunosuppressive drugs were used. Results: Ten rats died during the postoperative period. In 16 rats, the transplanted system had survived completely at the conclusion of the study. In each of the study groups, complete survival of the uterus and ovaries was noted in 8 rats (34.8% in the study group and 72.8% in the control group). In all rats except 1, histopathologic examination did not reveal any signs of the classic criteria for tissue rejection reaction. The lack of revascularization, nonspecific signs of inflammation, and the presence of large granular lymphocytes and natural killer cells were reported. Conclusions: Our data indicated that the outcome of both allograft and homograft avascular en bloc transplant of vagino-utero-ovariectomy in rats was successful, and that immunologic rejection did not seem to have an important role in those procedures.
Alteration of Direct and Indirect Effects of Cytomegalovirus
(Başkent Üniversitesi, 2007-12) Kamar, Nassim; Rostaing, Lionel; Mengelle, Catherine
For recipients of a solid organ transplant, cytomegalovirus infection causes many pathological conditions including direct and indirect effects, most notably owing to the potency of the immunosuppressive medications used. Effects attributed to cytomegalovirus infection include graft rejection, decreased graft and patient survival rates, predisposition to other opportunistic infections, virally mediated malignancies, and various injuries specific to the transplanted organs (eg, accelerated coronary atherosclerosis following heart transplant, bronchiolitis obliterans syndrome in lung transplants, and vanishing bile-duct syndrome in liver allografts). Other indirect effects include posttransplant lymphoproliferative disorders, posttransplant new onset diabetes, and recurrence of hepatitis C virus infection. Direct effects are related to viral burden, whereas indirect effects may be observed even in the presence of low levels of cytomegalovirus replication. Being a function of the interaction between the virus and the host’s immune and inflammatory responses, the underlying indirect effects of viral infection are not completely understood. Whereas it has been shown that cytomegalovirus prophylaxis can decrease the direct and indirect effects of the virus, recent data indicate that pre-emptive therapy has no long-term impact upon the indirect effects. Prevention of cytomegalovirus-related indirect effects might be achieved only with prophylaxis.