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Mahmoud Sakr

Ischemic damage of the allograft liver is a major problem in clinical liver transplantation. Therefore the identification of hepatoprotective agents is a high priority at most liver transplantation programs. FK 506, a potent new... more
Ischemic damage of the allograft liver is a major problem in clinical liver transplantation. Therefore the identification of hepatoprotective agents is a high priority at most liver transplantation programs. FK 506, a potent new immunosuppressive agent has been reported to possess hepatotrophic activity. To evaluate the putative hepatotrophic activity of FK 506 on experimental hepatic ischemia, rats were subjected to a subtotal hepatectomy following experimental ischemia and subsequent rat survival was assessed. FK 506 (0.3 mg/Kg) administered intravenously 24 hours prior to the induction of hepatic ischemia, reduced the subsequent mortality rate from 100% among controls given saline to only 20% (P less than 0.001). This observation demonstrates that FK 506 enhances the regenerative response of the liver to ischemic injury and may, in addition to its immunologic activity have hepatotrophic activity as well.
... 11. Rogers DF, Boschetto P, Barnes PJ. Plasma exudation: correlation between Evans blue dye and radiolabeled albumin in guinea pig airways in vivo. ... 18. Arndt H, Kubes P, Granger D. Involvement of neutrophils in... more
... 11. Rogers DF, Boschetto P, Barnes PJ. Plasma exudation: correlation between Evans blue dye and radiolabeled albumin in guinea pig airways in vivo. ... 18. Arndt H, Kubes P, Granger D. Involvement of neutrophils in ischemia-reperfusion injury in the small intestine. ...
Pancreatic neuroendocrine tumors (P-NETs) are rare tumors having an incidence ranging between 4 and 12 per million of population [1]. They are usually grouped based on malignancy versus benignity, cell of origin, and functional status. On... more
Pancreatic neuroendocrine tumors (P-NETs) are rare tumors having an incidence ranging between 4 and 12 per million of population [1]. They are usually grouped based on malignancy versus benignity, cell of origin, and functional status. On account of malignancy versus benignity, histopathology cannot reliably differentiate between both categories. Distinction is based on demonstrating invasion of nearby organs, nodal, or distant metastasis, undoubtedly marking the tumor as “malignant” [2]. Neuroendocrine carcinomas are exceedingly rare with their incidence accounting for only 1.3 % of pancreatic cancers collectively. However, having a better outcome, they represent up to 10 % of prevalent pancreatic cancers [3].
Pregnancy has a profound, though reversible, effect on the thyroid gland and its functions. In pregnancy, iodide losses through the urine and the feto-placental unit contribute to a state of relative iodine deficiency. Thus, pregnant... more
Pregnancy has a profound, though reversible, effect on the thyroid gland and its functions. In pregnancy, iodide losses through the urine and the feto-placental unit contribute to a state of relative iodine deficiency. Thus, pregnant women require additional iodine intake; a daily iodine intake of 250 μg has been recommended. Uncorrected thyroid dysfunction in pregnancy has adverse effects not only on fetal health but also on maternal well-being and may even extend beyond pregnancy and delivery to affect neuro-intellectual development in the early life of the child. This chapter discusses hyperthyroidism, hypothyroidism, autoimmune thyroiditis during pregnancy, and postpartum thyroiditis. It also illuminates the impact of thyroid dysfunction on infertility, miscarriage, thyroid nodules, and thyroid cancer during pregnancy.
Systematic ethics work and ethics discussions may help practitioners handle the many ethical challenges and dilemmas that have been described in the scientific literature pertaining to nursing homes. This review is based on a selective... more
Systematic ethics work and ethics discussions may help practitioners handle the many ethical challenges and dilemmas that have been described in the scientific literature pertaining to nursing homes. This review is based on a selective literature search of relevant publications retrieved from PubMed and CINAHL. In addition, relevant articles from the Internet or reference lists of articles and books, and other sources were included. Several methods and ways of approaching the discussion of ethics, and the implementation of ethics work in nursing homes, were identified. Frequently used methods and models to address ethical challenges were ethics peer groups, ethics consultation, or ethics committees. In conclusion, systematic ethics work in nursing homes is needed. The implementation should be individualized to meet different needs, as well as geographical and cultural conditions.
 Regenerative medicine modalities provide promising alternatives to conventional reconstruction techniques but are still deficient after malignant tumor excision or irradiation due to defective vascularization.  We investigated the... more
 Regenerative medicine modalities provide promising alternatives to conventional reconstruction techniques but are still deficient after malignant tumor excision or irradiation due to defective vascularization.  We investigated the pattern of bone formation in axially vascularized tissue engineering constructs (AVTECs) after irradiation in a study that mimics the clinical scenario after head and neck cancer. Heterotopic bone generation was induced in a subcutaneously implanted AVTEC in the thigh of six male New Zealand rabbits. The tissue construct was made up of Nanobone (Artoss GmbH; Rostock, Germany) granules mixed with autogenous bone marrow and 80 μL of bone morphogenic protein-2 at a concentration of 1.5 μg/μL. An arteriovenous loop was created microsurgically between the saphenous vessels and implanted in the core of the construct to induce axial vascularization. The constructs were subjected to external beam irradiation on postoperative day 20 with a single dose of 15 Gy. Th...
Thyroid autotransplantation offers an attractive alternative to subtotal thyroidectomy and replacement therapy. However, it has not been sufficiently clinically investigated. Total thyroidectomy was performed for 20 patients with benign... more
Thyroid autotransplantation offers an attractive alternative to subtotal thyroidectomy and replacement therapy. However, it has not been sufficiently clinically investigated. Total thyroidectomy was performed for 20 patients with benign thyroid disorders, and at least 10 g of thyroid tissue were implanted intramuscularly. Graft monitoring was achieved through (99m) Tc scan at 2 months, free triiodothyronine (FT3), FT4, and thyroid-stimulating hormone (TSH) measurements at 1, 2, 4, 6, 8, 10, and 12 months postoperatively, and clinical examination. Grafts survived and gradually functioned in all patients to a variable extent after a latent period (mean (99m) Tc uptake = 1.28 ± 0.37%). Mean values for FT3, FT4, TSH at 12 months were 1.75 ± 0.48 pg/mL, 1.06 ± 0.26 ng/dL, and 28.08 ± 34.01 μIU/mL respectively. Thyroid autotransplantation restored euthyroid status in 33.3% of patients after 12 months. A role of age, operative time, and (99m) Tc-uptake in determining the final graft outcom...
Total thyroidectomy is increasingly accepted for the management of bilateral benign thyroid disorders. Postoperatively, patients require lifelong levothyroxine replacement therapy to avoid postoperative hypothyroidism, which besides the... more
Total thyroidectomy is increasingly accepted for the management of bilateral benign thyroid disorders. Postoperatively, patients require lifelong levothyroxine replacement therapy to avoid postoperative hypothyroidism, which besides the burden of compliance, has been proven to be associated with several long-term side effects. Heterotopic thyroid autotransplantation was proposed several decades ago to avoid the need for life-long postoperative replacement therapy with maintaining the autoregulatory mechanism of thyroxin production inside the body according to its needs. Available data regarding this topic in literature is relatively poor. Before applying thyroid autotransplantation on humans, several studies have been done on animals, where the autologous transplantations were found to be successful in almost all the cases, proved by follow up postoperative 8-week measurements of thyroid hormones and histopathological examination of the removed autografts. Regarding the clinical app...
Most of the studies on the incidence, pattern, and predictive factors of lymph node (LN) metastasis with papillary thyroid carcinoma (PTC) have been performed retrospectively and no common consensus has been reached regarding the... more
Most of the studies on the incidence, pattern, and predictive factors of lymph node (LN) metastasis with papillary thyroid carcinoma (PTC) have been performed retrospectively and no common consensus has been reached regarding the predictors for the involvement of level I LNs. This study was conducted prospectively to determine the incidence and the possible predictors of level I involvement in N1b PTC patients. The study included 30 consecutive patients with N1b stage of PTC. All the patients underwent neck dissection (ND) including level I. The relation between involvement of level I LNs and various clinicopathological variables was studied. Unilateral neck dissection was performed in 24 patients and bilateral neck dissection in six patients leading to 36 NDs. Level I was excised in all patients, with five specimens (14%) positive for metastasis. Levels II, III, IV, V, VI, and VII were positive in 52.8, 58.3, 58.3, 33.3, 63, and 22.2%, respectively. Level I involvement was significantly related to the number of lymph node levels affected (p = 0.003) and macroscopic extranodal invasion (p = 0.04). It was not related to the involvement of other individual levels, gender, age, size of the largest thyroid nodule, size of the largest LN involved, or histo-pathological variant of the tumor. This study suggests that including level I in therapeutic neck dissection for N1b PTC patients might be recommended in selected cases of multiple level involvement and macroscopic extranodal invasion requiring sacrifice of internal jugular vein, spinal accessory nerve, or sternomastoid muscle.
The effect of pretreatment with FK506 on renal ischemia and reperfusion (I/R) injury was investigated using a rat model. Animals were assigned to one of two groups (20 rats each). Group 1 animals (controls) received 0.5 ml saline while... more
The effect of pretreatment with FK506 on renal ischemia and reperfusion (I/R) injury was investigated using a rat model. Animals were assigned to one of two groups (20 rats each). Group 1 animals (controls) received 0.5 ml saline while group 2 animals received FK506 (0.3 mg/kg), administered intravenously 24 hr prior to the induction of renal ischemia. A 60-min period of ischemia of the right kidney was induced, and upon reperfusion a left nephrectomy was performed. Blood samples for estimation of BUN, creatinine, and tumor necrosis factor were collected on days 0 (preischemia), 1, 2, 3, 5, 7, and 10 (postischemia). Rats were sacrificed after day 10 and renal tissue was examined histologically. All animals survived the ischemic episode. FK506 pretreatment significantly reduced the serum levels of BUN (P less than 0.02), creatinine (P less than 0.02), and TNF (P less than 0.05) as compared with that seen in controls. Histologically, at day 10, the kidneys showed the expected sequelae of prior renal I/R with various degrees of tubular damage. However, no objective differences were evident between the two groups. Based upon these data, it can be concluded that (1) FK506 pretreatment ameliorates the functional renal injury associated with I/R, (2) renal ischemia induces the release of TNF, and (3) FK506 pretreatment results in a significant inhibition of TNF production. These data suggest that the release of TNF may be responsible for the increasing of BUN and creatinine levels seen after renal I/R and that pretreatment of renal donors with FK506 may improve renal function in the immediate post-transplant period.
Organ shortage facing the increasing success of liver transplantation has provoked research into the utilization of animal organs for clinical transplantation. The technique of whole-organ decellularization aims at the removal of the... more
Organ shortage facing the increasing success of liver transplantation has provoked research into the utilization of animal organs for clinical transplantation. The technique of whole-organ decellularization aims at the removal of the antigenic cellular content, thus evading the immune rejection cascade and the production of complex three-dimensional extracellular matrices of the entire organs with preservation of their intrinsic vascular networks rendering them transplantable. The aim of this study was the production of decellularized rabbit liver matrices by applying a simple, rapid perfusion decellularization technique and their characterization (both qualitatively and quantitatively). Decellularization of the caudate hepatic lobes of New Zealand white rabbits (n = 22) was achieved through sequential perfusion of the portal venous system with deionized water, 0.8% Triton X-100 and 0.8% sodium dodecyl sulphate (SDS). Decellularized specimens were characterized both qualitatively (histology, fluoroscopy, corrosion casting and scanning electron microscopy) and quantitatively (total collagen assay [colorimetric] and total DNA assay [Hoechst 33258]). A Student's t-test was used to compare quantitative laboratory results before and after decellularization. A probability (P) value of <0.05 was considered significant. Effective decellularization was achieved as proven by histology and quantitative assessment (DNA remnants <1.5%, P = 0.0009), while preserving 68% of the total collagen content (P = 0.003). Portal vascular network integrity was confirmed by fluoroscopy and corrosion casting. Scanning electron microscopy also confirmed the preservation of the three-dimensional architecture. Liver perfusion decellularization technique using both 0.8% Triton X-100 and 0.8% SDS is a simple and rapid technique, yielding efficiently decellularized liver matrices preserving their vascular integrity, 3D architecture and 68% of total collagen content.
Hurthle cell lesion is one of the most questionable clinico-pathological entities in most of its aspects. Literature has used the terms oncocytic, oxyphilic, Hurthle, and Ashkanazy interchangeably; what does each term denote? Who first... more
Hurthle cell lesion is one of the most questionable clinico-pathological entities in most of its aspects. Literature has used the terms oncocytic, oxyphilic, Hurthle, and Ashkanazy interchangeably; what does each term denote? Who first described these cells? What is the cell of origin? How much Hurthle cells should be present to define the lesion as Hurthle cell one? Is it possible to differentiate hyperplastic from neoplastic and benign from malignant Hurthle cell lesion on a non-histopathologic ground? Does it belong to follicular or to papillary neoplasms or should it be classified separately? Can we anticipate its clinical behavior or predict its outcome? How can we manage? We will try to answer these questions in light of the ongoing relevant arguments with the aim of resolving some uncertainties and suggesting how to solve others.
The present study was conducted to evaluate the use of the transverse rectus abdominis myocutaneous (TRAM) flap in immediate autologous soft tissue coverage of the large wound defect that results from some oncological problems and would... more
The present study was conducted to evaluate the use of the transverse rectus abdominis myocutaneous (TRAM) flap in immediate autologous soft tissue coverage of the large wound defect that results from some oncological problems and would be impossible to close by direct primary sutures. The study included patients with locally advanced breast cancer (LABC) (n = 24), post-mastectomy local recurrence (n = 10), post-mastectomy irradiation ulcer (n = 4), recurrent fibrosarcoma of the chest wall (n = 1), and a huge ulcerating malignant melanoma of the groin region (n = 1). All patients were female except for the patient with melanoma. Their ages ranged between 39-73 years with an average of 56.2 years. The lower TRAM flap was used in 24 patients and the middle in only six. Mesh re-inforcement of the abdominal wall was adopted in 14 patients (35%). The mean operating time was 2.5 h and the average postoperative hospital stay was 9.7 days (range, 7-12 days). Six patients (15%) had partial flap necrosis which healed after debridement and secondary sutures, and eight patients had wound sepsis (20%). No patient suffered from abdominal herniation, although four patients (10%) had an epigastric bulge postoperatively. During the 48.5 month follow-up period (range 36-56 months), three cases of local recurrence and four cases of distant metastases were encountered in the patients with LABC. Three of the latter died at 7, 11 and 12 months postoperatively. Based on these data, it may be concluded that the results of the TRAM flap for immediate coverage of the large post-extirpation defect in different oncological problems have been encouraging. No flaps were lost, no abdominal herniation was encountered, and overall complications were minimal.

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