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Cell therapy for facial anti-aging

Ebisawa K, Kato R, Okada M, Kamei Y, Mazlyzam AL, Narita Y, et al.

Med J Malaysia, 2008 Jul;63 Suppl A:41.
PMID: 19024974

Two types of cell therapy for facial anti-aging in my clinical experience are introduced in this presentation. One therapy is cultured gingival fibroblasts injection. This procedure lasts for at least one year, making it a good option for patients. The other is platelet rich plasma injection. The results of the preliminary data are promising, but not yet well understood. More clinical data and long-term follow-up is needed.

Matched MeSH terms: Gingiva/transplantation*; Mouth Mucosa/transplantation*
Cultured epidermal autografts in combination with MEEK Micrografting technique in the treatment of major burn injuries

Dorai AA, Lim CK, Fareha AC, Halim AS

Med J Malaysia, 2008 Jul;63 Suppl A:44.
PMID: 19024976

The treatment of major burn injuries are a formidable challenge to the burn surgeon. Early aggressive surgery for deep to full thickness burn injuries is vital in the prevention of infection. The ultimate goal in major burn injuries is to prevent the onset of multi-resistant organisms and achieve early wound cover. The field of tissue engineering can help to expedite the healing of these burn wounds. The development of keratinocyte culture delivery system can be used clinically to fasten the healing process and save many lives.

Matched MeSH terms: Transplantation, Autologous*; Skin Transplantation
Social and cultural aspects of organ donation in Asia

Woo KT

Ann Acad Med Singap, 1992 May;21(3):421-7.
PMID: 1416796

In Asian countries, it is more difficult to obtain cadaver kidneys for renal transplantation because of certain socio-cultural beliefs and customs. The issues affecting living related kidney donation are more social than cultural. This is due to the web of family pressures and personal conflicts for both donor and recipient surrounding the donation. Important misconceptions and fears are: fear of death, the belief that removal of organ violates sanctity of decreased, concern about being cut up after death, desire to be buried whole, dislike of idea of kidneys inside another person, wrong concept of brain death, and the idea of donation being against religious conviction. In Singapore, with the introduction of the Human Organ Transplant Act (HOTA) in 1988, the number of cadaveric transplants have increased, including those from the Medical Therapy Act (MTA). HOTA and education have played pivotal roles in bringing about an increased yield of cadaveric kidneys. With the availability of living unrelated donor (LUD) transplants in India, our living related donor (LRD) transplant programme has suffered, because patients would rather buy a kidney from overseas than get a relative to donate one. Patients are also going to China for overseas cadaveric transplants where the kidneys come from executed convicts. People in countries like Hong Kong, Japan and the Philippines share the same Asian tradition of not parting with their organs after death. Muslim countries like Malaysia require the deceased to have earlier pledged his kidneys for donation prior to death before they can be harvested for transplantation at death.

Matched MeSH terms: Kidney Transplantation/legislation & jurisprudence; Kidney Transplantation/trends*
Fulltext Relationship between cell number and clinical outcomes of autologous bone-marrow mononuclear cell implantation in critical limb ischemia

Yusoff FM, Kajikawa M, Takaeko Y, Kishimoto S, Hashimoto H, Maruhashi T, et al.

Sci Rep, 2020 11 16;10(1):19891.
PMID: 33199760 DOI: 10.1038/s41598-020-76886-6

Cell therapy using intramuscular injections of autologous bone-marrow mononuclear cells (BM-MNCs) improves clinical symptoms and can prevent limb amputation in atherosclerotic peripheral arterial disease (PAD) patients with critical limb ischemia (CLI). The purpose of this study was to evaluate the effects of the number of implanted BM-MNCs on clinical outcomes in atherosclerotic PAD patients with CLI who underwent cell therapy. This study was a retrospective observational study with median follow-up period of 13.5 years (range, 6.8-15.5 years) from BM-MNC implantation procedure. The mean number of implanted cells was 1.2 ± 0.7 × 109 per limb. There was no significant difference in number of BM-MNCs implanted between the no major amputation group and major amputation group (1.1 ± 0.7 × 109 vs. 1.5 ± 0.8 × 109 per limb, P = 0.138). There was also no significant difference in number of BM-MNCs implanted between the no death group and death group (1.5 ± 0.9 × 109 vs. 1.8 ± 0.8 × 109 per patient, P = 0.404). Differences in the number of BM-MNCs (mean number, 1.2 ± 0.7 × 109 per limb) for cell therapy did not alter the major amputation-free survival rate or mortality rate in atherosclerotic PAD patients with CLI. A large number of BM-MNCs will not improve limb salvage outcome or mortality.

Matched MeSH terms: Transplantation, Autologous; Bone Marrow Transplantation/methods*
Effect of keratin-gelatin and bFGF-gelatin composite film as a sandwich layer for full-thickness skin mesh graft in experimental dogs

Thilagar S, Jothi NA, Omar AR, Kamaruddin MY, Ganabadi S

J Biomed Mater Res B Appl Biomater, 2009 Jan;88(1):12-6.
PMID: 18161832

Skin grafts are indicated when there is a major loss of skin. Full-thickness skin graft is an ideal choice to reconstruct defect of irregular surface that is difficult to immobilize. Full-thickness mesh grafts can be applied to patch large skin defect when there is less donor site in extensively traumatized and burned surgical patients. The concept of using natural biomaterials such as keratin, basic fibroblast growth factor is slowly gaining popularity in the field of medical research to achieve early healing. The main objective of this study is to evaluate the efficacy of gelatin conjoined with keratin processed from the poultry feather and commercially available basic fibroblast growth factor (bFGF) as a sandwich layer in promoting the viability of full-thickness skin mesh grafts. The efficacy was assessed from the observation of clinical, bacteriological, and histopathological findings in three groups of experimental dogs. The clinical observations such as color, appearance and discharge, and hair growth were selected as criteria which indicated good and early acceptance of graft in keratin-gelatin (group II). On bacteriological examination, Staphylococcus aureus and Proteus was identified in few animals. Histopathological study of the patched graft revealed early presences of hair follicles; sebaceous gland, and normal thickness of the epidermis in keratin-gelatin in group II treated animals compared with other group (group I-control, group III-bFGF-gelatin).

Matched MeSH terms: Skin Transplantation/instrumentation*; Skin Transplantation/methods
Fulltext Fibrin glue versus sutures for conjunctival autografting in primary pterygium surgery

Romano V, Cruciani M, Conti L, Fontana L

Cochrane Database Syst Rev, 2016 12 02;12:CD011308.
PMID: 27911983 DOI: 10.1002/14651858.CD011308.pub2

BACKGROUND: Pterygium, a growth of the conjunctiva over the cornea, is a progressive disease leading in advanced stages to visual impairment, restriction of ocular motility, chronic inflammation and cosmetic concerns. Surgical removal is the treatment of choice, but recurrence can be a problem. Currently the best surgical option in terms of recurrence is conjunctival autograft. To date the most common surgical methods of attaching conjunctival autografts to the sclera are through suturing or fibrin glue. Each method presents its own advantages and disadvantages. Sutures require considerable skill from the surgeon and can be associated with a prolonged operation time, postoperative discomfort and suture-related complications, whereas fibrin glue may give a decreased operation time, improve postoperative comfort and avoid suture-related problems.
OBJECTIVES: To assess the effectiveness of fibrin glue compared to sutures in conjunctival autografting for the surgical treatment of pterygium.
SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2016), Embase (January 1980 to October 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 14 October 2016.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) in any setting where fibrin glue was compared with sutures to treat people with pterygium.
DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results, assessed trial quality, and extracted data using standard methodological procedures expected by Cochrane. Our primary outcome was recurrence of pterygium defined as any re-growth of tissue from the area of excision across the limbus onto the cornea. The secondary outcomes were surgical time and complication rate. We graded the certainty of the evidence using GRADE.
MAIN RESULTS: We included 14 RCTs conducted in Brazil, China, Egypt, India, Malaysia, New Zealand, Philippines, Saudi Arabia, Sweden and Turkey. The trials were published between 2004 and 2016, and were assessed as a mixture of unclear and low risk of bias with three studies at high risk of attrition bias. Only adults were enrolled in these studies.Using fibrin glue for the conjunctival autograft may result in less recurrence of pterygium compared with using sutures (risk ratio (RR) 0.47, 95% CI 0.27 to 0.82, 762 eyes, 12 RCTs; low-certainty evidence). If pterygium recurs after approximately 10 in every 100 surgeries with sutures, then using fibrin glue may result in approximately 5 fewer cases of recurrence in every 100 surgeries (95% CI 2 fewer to 7 fewer cases). Using fibrin glue may lead to more complications compared with sutures (RR 1.92; 95% CI 1.22 to 3.02, 11 RCTs, 673 eyes, low-certainty evidence). The most common complications reported were: graft dehiscence, graft retraction and granuloma. On average using fibrin glue may mean that surgery is quicker compared with suturing (mean difference (MD) -17.01 minutes 95% CI -20.56 to -13.46), 9 RCTs, 614 eyes, low-certainty evidence).
AUTHORS' CONCLUSIONS: The meta-analyses, conducted on people with pterygium in a hospital or outpatient setting, show fibrin glue may result in less recurrence and may take less time than sutures for fixing the conjunctival graft in place during pterygium surgery. There was low-certainty evidence to suggest a higher proportion of complications in the fibrin glue group.

Matched MeSH terms: Conjunctiva/transplantation*; Transplantation, Autologous
Fulltext Total proximal ureter substitution using buccal mucosa

Fahmy O, Schubert T, Khairul-Asri MG, Stenzl A, Gakis G

Int J Urol, 2017 04;24(4):320-323.
PMID: 28208217 DOI: 10.1111/iju.13307

The surgical treatment of a long proximal ureteral stricture is a challenging situation for reconstructive surgeons. Despite the underlying morbidities, ileal interposition and autotransplantation are the options available to treat complex cases of long segment ureteral stricture. Buccal mucosa has shown excellent results in urethroplasty. However, its use in ureteral reconstruction is infrequent. We report on a 64-year-old female patient with multiple comorbidities and prior abdominal surgeries for Crohn's disease who underwent a successful total substitution of a long segment of the proximal ureter using buccal mucosa. Regular postoperative isotope scans showed improvement in renal function. Based on the pleasant outcome of this case and review of the literature, buccal mucosa might be a viable option with low morbidity in selected cases.

Matched MeSH terms: Mouth Mucosa/transplantation*; Ureter/transplantation*
Fulltext Application of platelet rich fibrin for management of an electrosurge induced osteonecrosis involving maxillary alveolus

Suresh N, Chandrasekaran B, Muthusamy S, Kannan S, Muthu K

Singapore Dent J, 2015 Dec;36:39-43.
PMID: 26684495 DOI: 10.1016/j.sdj.2014.11.004

BACKGROUND: Application of principles of electrocautery for hemostasis dates back to prehistoric times. Its modern implementation in various fields of general and head and neck surgeries have been well documented. However its usage in minor oral surgical procedures has gained popularity only recently. Complications associated with electro-surgery in the dental field are relatively rare and there is insufficient literature on its management.
CASE REPORT: We present a case report on management of an electrosurgery induced osteonecrosis involving maxillary alveolus of left premolars.
DISCUSSION: Inadvertent contact of the electrosurgery tip on bone can result in necrosis making it necessary to remove the sequestrum and graft the defect. Platelet rich fibrin in combination with bone grafts have been well documented to provide successful periodontal regeneration.
CLINICAL IMPLICATIONS: Our aim of presenting this report is to create awareness among the health care providers regarding electrosurgical injuries. To our knowledge, this is the first time platelet rich fibrin has been used in the management of intraoral electrosurgical injury. Combining bone grafts with platelet rich fibrin is a good alternative as it can be done with relative ease and predictable outcome.

Matched MeSH terms: Bone Transplantation
Fulltext Albinism and lung fibrosis in a young man - the first case of adult Hermansky-Pudlak Syndrome reported in Malaysia

Liza AF, Aziah AM

Med J Malaysia, 2012 Dec;67(6):620-1.
PMID: 23770959

A young gentleman of Indian descent with oculacutaneous albinism (OCA) was found to have severe pulmonary fibrosis at first presentation. Following investigations, he was diagnosed with Hermansky-Pudlak Syndrome (HPS). It is a genetic condition characterised by albinism, bleeding diathesis and multisystem disorder observed in individuals of particular descents. Although there is no curative treatment apart from lung transplantation, preventive measures to minimise pulmonary insult may change the natural history of the disease. Therefore HPS should be actively sought, monitored and risk factors addressed in individuals with OCA and bleeding diathesis particularly those of Indian descent as they may develop serious complications such as pulmonary fibrosis in the future.

Matched MeSH terms: Lung Transplantation
Fulltext The potential of intra-articular injection of chondrogenic-induced bone marrow stem cells to retard the progression of osteoarthritis in a sheep model

Al Faqeh H, Nor Hamdan BM, Chen HC, Aminuddin BS, Ruszymah BH

Exp Gerontol, 2012 Jun;47(6):458-64.
PMID: 22759409 DOI: 10.1016/j.exger.2012.03.018

In recent years, the use of bone marrow mesenchymal stem cell (BMSC) implantation has provided an alternative treatment for osteoarthritis. The objective of this study is to determine whether or not an intra-articular injection of a single dose of autologous chondrogenic induced BMSC could retard the progressive destruction of cartilage in a surgically induced osteoarthritis in sheep. Sheep BMSCs were isolated and divided into two groups. One group was cultured in chondrogenic media containing (Ham's F12:DMEM, 1:1) FD+1% FBS+5 ng/ml TGFβ3+50 ng/ml IGF-1 (CM), and the other group was cultured in the basal media, FD+10% FBS (BM). The procedure for surgically induced osteoarthritis was performed on the donor sheep 6 weeks prior to intra-articular injection into the knee joint of a single dose of BMSC from either group, suspended in 5 ml FD at density of 2 million cells/ml. The control groups were injected with basal media, without cells. Six weeks after injection, gross evidence of retardation of cartilage destruction was seen in the osteoarthritic knee joints treated with CM as well as BM. No significant ICRS (International Cartilage Repair Society) scoring was detected between the two groups with cells. However macroscopically, meniscus repair was observed in the knee joint treated with CM. Severe osteoarthritis and meniscal injury was observed in the control group. Interestingly, histologically the CM group demonstrated good cartilage histoarchitecture, thickness and quality, comparable to normal knee joint cartilage. As a conclusion, intra-articular injection of a single dose of BMSC either chondrogenically induced or not, could retard the progression of osteoarthritis (OA) in a sheep model, but the induced cells indicated better results especially in meniscus regeneration.
Study site: Universiti Kebangsaan Malaysia, Kuala Lumpur

Matched MeSH terms: Bone Marrow Transplantation/methods; Mesenchymal Stem Cell Transplantation/methods*
Fulltext Contemporary surgical management of advanced end stage emphysema: an evidence based review

Sachithanandan A, Badmanaban B

Med J Malaysia, 2012 Jun;67(3):253-8.
PMID: 23082412 MyJurnal

Emphysema is a progressive unrelenting component of chronic obstructive pulmonary disease and a major source of mortality and morbidity globally. The prevalence of moderate to severe emphysema is approximately 5% in Malaysia and likely to increase in the future. Hence advanced emphysema will emerge as a leading cause of hospital admission and a major consumer of healthcare resources in this country in the future. Patients with advanced disease have a poor quality of life and reduced survival. Medical therapy has been largely ineffective for many patients however certain subgroups have disease amenable to surgical palliation. Effective surgical therapies include lung volume reduction surgery, lung transplantation and bullectomy. This article is a comprehensive evidence based review of the literature evaluating the rationale, efficacy, safety and limitations of surgery for advanced emphysema highlighting the importance of meticulous patient selection and local factors relevant to Malaysia.

Matched MeSH terms: Lung Transplantation
The use of glycerol-preserved skin allograft in conjunction with reconstructive and flap surgery: seven years of experience

Saad AZ, Halim AS, Khoo TL

J Reconstr Microsurg, 2011 Feb;27(2):103-8.
PMID: 20976667 DOI: 10.1055/s-0030-1268208

Major reconstructive surgery may be extensive and prolonged, and it may cause edema and compromise the flap pedicle if closed under tension. Glycerol-preserved skin allograft (GPA) can provide a means for tension-free closure and temporary cover of the wound. Seven years of analysis on GPA used in conjunction with major reconstruction was undertaken to highlight its indications, results, and outcomes. Forty-seven patients were included, aged between 9 and 73 years. Majority of patients had reconstruction following tumor resection and trauma. The main indication for use of GPA was temporary, loose cover of the wound in 44% of cases; flap pedicle protection in 31% of cases; donor site wound cover in 10%; flap monitoring in one case; and management of flap-related complications in 6% of cases. Free flap reconstruction was performed in 72% of cases. In conclusion, GPA is a useful adjunct in reconstructive surgery. It can be used temporarily to allow tension-free wound closure, as well as to protect the flap pedicle until edema subsides and the pedicle becomes stable. This latter approach allows secondary wound closure and good esthetic outcome.

Matched MeSH terms: Transplantation, Homologous; Skin Transplantation/adverse effects; Skin Transplantation/methods*
Adult stem cells: a clinical update

Totey S, Totey S, Pal R, Pal R

J Stem Cells, 2009;4(2):105-21.
PMID: 20232596

There has been unprecedented interest in stem cell research mainly because of their true potential and hope that they offer to the patients as a cell therapy with the prospect to treat hitherto incurable diseases. Despite the worldwide interest and efforts that have been put in this research, major fundamental issues are still unresolved. Adult stem cells such as hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) are already under clinical applications and there are several examples of plasticity and self-renewal where adult stem cells or their precursor cells can be re-programmed by extra cellular cues or internal cues to alter their character in a way that could have important application for cell therapy and regenerative medicine. From a clinical perspective, no other area of stem cell biology has been applied as successfully as has transplantation of bone marrow stem cells and cord blood stem cells for the treatment of hematological diseases. In the last few years, research in stem cell biology has expanded staggeringly, engendering new perspectives concerning the identity, origin, and full therapeutic potential of tissue-specific stem cells. This review will focus on the use of adult stem cells, its biology in the context of cell plasticity and their therapeutic potential for repair of different tissues and organs.

Matched MeSH terms: Hematopoietic Stem Cell Transplantation; Mesenchymal Stem Cell Transplantation; Adult Stem Cells/transplantation
Fulltext Quantitative and qualitative evaluation of sural nerve graft donor site

Ng SS, Kwan MK, Ahmad TS

Med J Malaysia, 2006 Dec;61 Suppl B:13-7.
PMID: 17600987

This study is designed to evaluate twenty patients after sural nerve harvest using the single longitudinal incision method. The area of sensory loss to pin prick was assessed by the authors at different intervals. Donor site factors, scar cosmesis, functional status and complications were assessed using a questionnaire. The mean area of anaesthesia at one month was 65 cm2 and it had reduced by 77% to 15 cm2 at one and a half years. The mean area of reduced sensation was 49 cm2 at one month and it increased by 18% to 58 cm2 over the same period. Therefore, the total area of sensory deficit was reduced by 36% from 114 cm2 at one month to 73 cm2 at one and a half years. Subjective patient evaluation indicated moderate level of pain during immediate post surgical period, which reduced significantly at one month. A low level of neuroma symptoms was recorded throughout the study period. At a mean follow-up period of two years, there was no area of anaesthesia in 50% of the patients. Mean area of anaesthesia for all patients was 12 cm2 and mean area of reduced sensation was 55 cm2. Subjective patient evaluation indicated a low level of pain, neuroma symptoms and numbness over the sural nerve sensory distribution. Twenty five percent of the patients were not satisfied with the scar appearance. Function and daily activities were not affected significantly. No surgical complications were observed.

Matched MeSH terms: Sural Nerve/transplantation*; Organ Transplantation/standards*
The influence of CYP3A gene polymorphisms on cyclosporine dose requirement in renal allograft recipients

Eng HS, Mohamed Z, Calne R, Lang CC, Mohd MA, Seet WT, et al.

Kidney Int, 2006 May;69(10):1858-64.
PMID: 16612333

Cyclosporine is a substrate of cytochrome P-450 3A (CYP3A) subfamily of enzymes and characterized by a narrow therapeutic range with wide interindividual variation in pharmacokinetics. A few single-nucleotide polymorphisms detected in CYP3A genes have been shown to correlate significantly with the CYP3A protein expression and activity. We therefore postulated that these polymorphisms could be responsible for some of the interindividual variation in cyclosporine pharmacokinetics. The objective of our study is to determine correlation if any between single-nucleotide polymorphisms of CYP3A5 and CYP3AP1 on cyclosporine dose requirement and concentration-to-dose ratio in renal allograft recipients. Cyclosporine-dependent renal allograft recipients were genotyped for CYP3A5 A6986G and CYP3AP1 G-44A. The cyclosporine dosages prescribed and the corresponding cyclosporine trough levels for each patient were recorded so that cyclosporine dose per weight (mg/kg/day) and concentration-to-dose ratio (C(0)/D, whereby C(0) is trough level and D is daily dose per weight) could be calculated. A total of 67 patients were recruited for our study. The dose requirement for 1, 3, and 6 months post-transplantation ranged 2.3-11.4, 1.0-9.0, and 1.4-7.2 mg/kg/day, respectively. Patients with *1*1*1*1 (n=5) CYP3A5- and CYP3AP1-linked genotypes needed higher dose of cyclosporine compared to patients with *1*3*1*3 (n = 27) and *3*3*3*3 (n = 33) linked genotypes in months 3 and 6 post-transplantation (P < 0.016). The identification of patients with *1*1*1*1 by CYP3A5 and CYP3AP1 genotyping may have a clinically significant and positive impact on patient outcome with reduced rejection rate by providing pretransplant pharmacogenetic information for optimization of cyclosporine A dosing.

Matched MeSH terms: Transplantation, Homologous*; Kidney Transplantation/classification*
Fulltext Early complication following long bone reconstruction using vascularised fibula graft

Imran Y, Zulmi W, Halim AS

Med J Malaysia, 2004 Dec;59 Suppl F:35-8.
PMID: 15941158

Long bone reconstruction using vascularized fibula graft is becoming more popular despite the difficulties and its post-operative complications. We reviewed our early experience dealing with vascularized fibula graft for the management of massive long bone defect. Thirteen patients had undergone long bone reconstruction using vascularized fibula graft. Early complications that had been encountered include superficial wound infection (23%), transient common peroneal nerve palsy (23%), stage 1 bed sore (7.7%), anastomotic venous thrombosis (30.8%), DIVC (15.4%), flap loss and amputation (7.7%), and reactive psychiatric problem (7.7%). The early complications following this procedure are comparable with other major orthopaedic surgery and most of them are minor and treatable. The complication rates are also comparable with similar surgery done elsewhere.

Matched MeSH terms: Fibula/transplantation*; Bone Transplantation*
Effects of CYP3A5 Genetic Polymorphism on the Pharmacokinetics of Tacrolimus in Renal Transplant Recipients

Mac Guad R, Zaharan NL, Chik Z, Mohamed Z, Peng NK, Adnan WA

Transplant Proc, 2016 Jan-Feb;48(1):81-7.
PMID: 26915847 DOI: 10.1016/j.transproceed.2016.01.001

BACKGROUND: The aim of this study was to compare the within-patient variability trough levels (Co), dose-adjusted Co, and dose requirements of Prograf and Advograf with CYP3A5 polymorphisms in Malaysia renal transplant recipients.
METHODS: Stable post-renal transplantation patients switched from Prograf to Advograf were retrospectively identified from University Malaya Medical Centre (n = 28). Co and concomitant tacrolimus dose 6 months preconversion and postconversion were examined. CYP3A5 was genotyped using reverse transcriptase polymerase chain reaction. Wilcoxon signed rank test and Mann-Whitney U test were used to compare Co and dose between formulations and according to genotypes.
RESULTS: There was a significant difference in the whole-blood tacrolimus Co between the 2 groups (6.16 ± 1.74 ng/mL vs 4.90 ± 1.06 ng/mL; P = .0001). The mean daily maintenance dose of Prograf was 3.9 ± 2.0 mg/kg (0.06 mg/kg/d), which was reduced to 3.3 ± 1.7 mg/d (0.04 mg/kg/d) with Advograf (P = .01). The mean maintenance dose of tacrolimus required for those with CYP3A5*1/*1 (high-expressive) was significantly higher than those with CYP3A5*1/*3 (intermediate-expressive) and CYP3A5*3/*3 (low-expressive) (P < .01) for both formulations. Comparing those with CYP3A5*1/*1, the average dose-adjusted Co was significantly higher in patients with CYP3A5*3/*3 with Advograf (P < .05).
CONCLUSIONS: The requirement for daily maintenance dose was higher in those with CYP3A5*1/*1 variants in both tacrolimus formulations in the Malaysian patients. Furthermore, those with CYP3A5*3/*3 demonstrated significantly higher dose-adjusted Co with Advograf.

Matched MeSH terms: Kidney Transplantation
Autoimmune thrombocytopenia and neutropenia after autologous peripheral blood stem cell transplantation

Wahid FS, Cheong SK, Sivagengei K

Acta Haematol., 2002;107(4):237-8.
PMID: 12053154
Matched MeSH terms: Transplantation, Autologous/adverse effects*; Hematopoietic Stem Cell Transplantation/adverse effects*
Intra-arterial allogeneic mesenchymal stem cells for critical limb ischemia are safe and efficacious: report of a phase I study

Das AK, Bin Abdullah BJ, Dhillon SS, Vijanari A, Anoop CH, Gupta PK

World J Surg, 2013 Apr;37(4):915-22.
PMID: 23307180 DOI: 10.1007/s00268-012-1892-6

BACKGROUND: Critical limb ischemia (CLI) caused by peripheral arterial disease is associated with significant morbidity and mortality. This condition is associated with a 30 % amputation rate as well as mortality levels which might be as high as 25 %. There is no pharmacological therapy available, but several reports have suggested that mesenchymal stem cells (MSCs) may be a useful therapeutic option.
METHODS: This study, done at a university hospital, evaluated 13 patients for a phase I trial to investigate the safety and efficacy of intra-arterial MSCs in CLI patients. Eight patients with ten affected limbs were recruited for the study. As two patients (three limbs) died of ischemic cardiac events during the 6-month follow-up period, seven limbs were finally evaluated for the study.
RESULTS: There was significant pain relief. Visual analog scale (VAS) scores decreased from 2.29 ± 0.29 to 0.5 ± 0.34 (p < 0.05), ankle brachial pressure index (ABPI) increased significantly from 0.56 ± 0.02 to 0.67 ± 0.021 (p < 0.01), and transcutaneous oxygen pressure (TcPO2) also increased significantly in the foot from 13.57 ± 3.63 to 38 ± 3.47. Similar improvement was seen in the leg as well as the thigh. There was 86 % limb salvage and six of seven ulcers showed complete or partial healing.
CONCLUSION: It was concluded that intra-arterial MSCs could be safely administered to patients with CLI and was associated with significant therapeutic benefits.

Matched MeSH terms: Bone Marrow Transplantation/methods*; Mesenchymal Stem Cell Transplantation/methods*
Fulltext The therapeutic potential of stem cells and progenitor cells for the treatment of Parkinson's disease

Liau MT, Amini F, Ramasamy TS

Tissue Eng Regen Med, 2016 Oct;13(5):455-464.
PMID: 30603427 DOI: 10.1007/s13770-016-9093-2

Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is usually seen in those above 50 years old. Current medical treatments only provide symptomatic relief but cannot cure the disease. There are claims that PD can be cured by stem cell transplant. The present study is aimed to assess the clinical potency and safety of stem cell in treating PD. A total of eleven articles were included for analysis, with four randomised control trials (RCTs), five non-RCTs and 2 follow up studies. All the four non-RCTs showed improvement of Unified Parkinson's Disease Rating Scale with no adverse events. However, results from RCTs showed no significant differences in the rating score among the transplant group and the Sham surgery group. The secondary analysis of one study showed a significant improvement of the rating score in those patients aged 60 and younger. Transplant group also associated with an overall higher incidence of adverse events. In conclusion, the RCTs and non-RCTs produced opposite results. When the studies were performed as non-RCTs in small number of patients, they showed promising result in the patients. It could say that currently the use of stem cell/progenitor cells in treating PD need much research despite having the implanted stem cell to be able to survive and integrated. The survival of implanted dopamine neurons in the striatum, however, does not indicate a success in correcting PD symptoms. Further investigations will shed light on the application and mechanism of action of stem cells in treating PD.
Electronic Supplementary Material: Supplementary material is available for this article at 10.1007/s13770-016-9093-2 and is accessible for authorized users.

Matched MeSH terms: Stem Cell Transplantation

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