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Volumen 11, Ausgabe 1 (2017)

Kurze Kommunikation

Significance of De novo Donor-Specific Anti-HLA Antibodies in Renal Transplantation: A Single Center Experience

Kozaki K, Adachi N, Sasaki T, Okada A, Kato T, Yuzawa K, Inadome Y and Terashima T

T cell-mediated rejection (TCMR) became controllable, and the long-term renal graft survival came to be obtained by the recent progress and innovation of the immuno-suppressants. Whereas the prophylaxis and control of antibody-mediated rejection (ABMR) caused by donor-specific anti-HLA antibody (DSA) are still insufficient and affect the long-term renal graft survival. DSA was classified roughly as follows: preexisting DSA existed in the patients before renal transplantation (RTx), and de novo DSA produced in the patients after RTx. There are many reports about the effect that preexisting DSA gives to a renal graft, and the treatment for ABMR with preexisting DSA is established to some degree. In contrast to preexisting DSA, it cannot be said that de novo DSA are considered enough at present. In this study, we examined the impact that de novo DSA gave to a renal graft in 40 RTx patients under treatment in our hospital. Although there was no significant difference as to the renal graft function in DSA positive and negative group, the renal graft survival showed the tendency that was better in a DSA negative group than a positive group (85% vs. 55%, P=0.0553). We perform monitoring of the de novo DSA positively and should contribute to the prognosis improvement of the renal graft in future.

Kleiner Rückblick

Significance of the Difference in the Size of Liver Tumors in the Management of Patients with Colorectal Liver Metastases

Kosuke Ichida, Koichi Suzuki, Taro Fukui, Yuji Takayama, Nao Kakizaw, Yuta Muto, Takaharu Kato, Fumi Hasegawa, Fumiaki Watanabe, Yuji Kaneda, Rina Kikugaw, Masaaki Saito, Shingo Tsujinaka, Kazushige Futsuhara, Yasuyuki Miyakura, Hiroshi Nod, Hirokazu Kiyozaki and Toshiki Rikiyama

Background: The combination of chemotherapy and surgery is currently accepted for the treatment of patients with technically resectable colorectal liver metastases. It is, however, hard to determine which of these modalities should be the forward treatment. In this study, we assessed the usefulness of the difference in tumor size assessed in pretherapeutic imaging in the selection of chemotherapy in these patients.

Methods: We present a retrospective review of 80 consecutive colorectal liver metastases without extrahepatic tumors. The relapse-free survival (RFS), progression-free survival (PFS) and overall survival (OS) were evaluated and compared between patients who underwent surgery (n=66) and chemotherapy (n=14) according to clinical features. In particular, we addressed pretherapeutic imaging studies including the distribution and number of metastatic liver tumors. In addition, the ratio of tumor size (largest to smallest tumor) was calculated; two groups classified as R<5 (ratio <5) and R ≥ 5 (ratio ≥ 5) were compared.

Results: Univariate analysis was performed in the surgery group; significant differences in RFS were found regarding time of occurrence, the number of tumors and the ratio of tumor diameters. Multivariate analysis showed that the ratio of tumor size, R ≥ 5, was the only independent prognostic risk factor concerning both RFS and OS. We then compared the outcome of patients with prognostic risk factors between surgery and chemotherapy. Surgery achieved significantly better OS than chemotherapy, with the exception of the R ≥ 5 group. No difference in OS, in addition to RFS and PFS, was seen in the R ≥ 5 groups regardless of treatment.

Conclusion: CRC patients with resectable liver metastases with R ≥ 5 showed no significant difference in outcome using surgery or chemotherapy. Chemotherapy could be used as an alternative to forward surgery to address oncological concerns such as the presence of latent metastases or poor treatment outcome in these patients.

Kleiner Rückblick

Colon Cancer and Immunotherapy: CD40 Ligand as a Potential Therapeutic Target

Orfanos S, Patelis N, Davakis S, Vailas M, Damaskos C, Margonis GA, Pikoulis E and Antoniou E

CD40, a member of the tumor necrosis factor (TNF) superfamily, it is broadly expressed on a variety of cells. There are studies to suggest that the expression of CD40 is correlated to several malignancies, while its innate therapeutic qualities are yet to be confirmed. Colon cancer is one of the most common cancers, while little can be done for the patients with advance colon cancer even at the presence time. CD40 are present in the colon cancer, and are a possible therapeutic immunotherapy target in order to enhance the overall survival rates of the patients with advanced disease.

Fallbericht

Inverted Palmaris Longus Accessory Muscle: A Case Report

Athar S, Howles S and Ashwood N

We present a case of accessory palmaris longus where muscle belly was distal to the tendon and not causing the median nerve compression. This was an incidental finding during the investigation of a wrist pain.

Kleiner Rückblick

Genomics, Epigenetics and Molecular Considerations in Esophageal Adenocarcinoma: What You Need to Know?

Schizas D, Mylonas KS, Patelis N, Sioulas A and Liakakos T

Esophageal malignancies are usually encountered in patients over 50 years old and are associated with significant morbidity and mortality. Efforts to improve patient outcomes are slowly shifted towards unravelling the molecular basis of esophageal cancer as this approach could lead to designing individualized treatment protocols and implementing precision medicine paradigms. Our aim was to present recent advances in esophageal adenocarcinoma genomics, epigenetics and molecular biology with regards to their role on disease pathophysiology, patient outcomes and applications to clinical care. Disease progression is correlated with missense mutations and in-frame deletions of EGFR, as well as with upregulation of a variety of genes (CXCL1 CXCL3, GATA6 and DMBT1), microsatellite instability and telomerase overexpression. On the other hand, p53 loss of heterozygosity as well as HER2 and c-MYC amplifications tend to develop in later stages of the disease and are associated with poor prognosis. Downregulation of CDKN2A, e-cadherin, SMAD4, RUNX3 and aneuploidy/tetraploidy are also correlated with unfavorable outcomes. Lastly, p53 immunohistochemistry and methylation panels are already being applied in clinical practice.

Rezensionsartikel

Gene Therapy of Parkinson’s Disease

Malik A

Parkinson’s is second most common neurological disorder in the world having both sporadic and familial cases. Present Parkinson’s disease genetics taxonomy specifies 18 chromosomal regions that are also called chromosomal locus which are termed PARK. Gene therapy i.e., Use of genes as medicine, is effective and newly discovered treatment of many Central nervous system disorders including Parkinson’s disease. Direct injection was also performed but it does not give suitable results. So, scientist feel need of using different vectors for efficient delivery of genes in Central nervous system. Hence gene therapy of Parkinson’s disease involves use of both viral and non-viral vectors but viral vectors shows efficient results. Frequently used vectors for therapy of Parkinson’s disease are Lentivirus and adeno associated virus. Using these vectors many successful experiments are performed on different animals. Parkin, Glial cell-derived neurotrophic factor (GDNF) and alpha synuclein are some of the successful products for therapy of Parkinson’s disease.

Fallbericht

Morphologic, Immunohistochemical and Molecular Analyses of a Huge Clear Cell Papillary Renal Cell Carcinoma

Raspollini MR, Ilaria M, Francesca C, Liang C, Rodolfo M and Antonio LB

Among the tumors of the kidney, the clear cell papillary renal cell carcinoma (CCPRCC) is a recently described entity. This tumor is well circumscribed, with a fibrous capsule, showing mostly a prominent cystic component and a diameter less than 4 cm. Necrosis is not a feature. Tumor cells are clear with low grade nuclei with a predominantly tubule-papillary architecture and immunohistochemical staining strongly positive for CK7, and for CA IX and negative for RACEMASE, features which differentiate this tumor from clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (papillary RCC). In these latter tumors, it has been reported, unlike the other two, no loss or gain of chromosomes 7 and Y, no chromosome 3p deletion, and no KRAS mutation. In this report, a huge clear cell papillary renal cell carcinoma case, 9 cm diameter, in a 42-year-old male is described. Pathologic diagnosis of the tumor was confirmed by immunohistochemical analysis including CD10, CA IX, CK7, RACEMASE, and 34 beta E12 stainings. Molecular detection of KRAS, BRAF, NRAS, PIK3CA, ALK, ERBB2, DDR2, MAP2K1, RET, and EGFR gene mutational analysis has also been performed. Molecular findings are in accordance with the speculation that the CCRCC is an indolent tumor which may be defined as low malignant potential. In fact, in the molecular analysis, none out of all genes evaluated showed mutation.

Fallbericht

Clinical and Genetic Analysis of Early-Onset Alzheimer's Disease in Two Chinese Han Families with Presenilin-1 Mutations

Ren Z, Xia M, Chen Z, Shi Y, Ma Q, Bai Y and Zhang J

Alzheimer’s disease is an autosomal dominant neurodegenerative disease manifested by core symptoms of cognitive decline and memory impairment. This progressive disorder with an insidious onset typically appears in older individuals, but may also affect young people, even in their 30s. It is well established that mutations in amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) cause Alzheimer’s disease. PSEN1 mutation is more common in Familial Alzheimer’s disease compared with PSEN2 and APP. Two patients fulfilling the NINCDS-ADRDA criteria for probable and definite Alzheimer’s disease were assessed. Two PSEN1 mutations (p.L392P and p.M233L) were identified from 2 probable early-onset familial Alzheimer’s disease (EOFAD) families, respectively. The p.L392P and p.M233L mutations were associated with prominent early onset, rapidly progressive dementia, and neurologic symptoms. Both p.L392P and p.M233L were predicted or confirmed to be pathogenic, and the p.L392P mutation in PSEN1 is the first report in China.

Meinung

Translational Stem Cell Research – A Marriage of Hope and Hype

Shah SM

The conventional medicine has failed to treat such disorders which arise by cell dysfunction or death, thus necessitating reimbursement of body’s natural regenerative power. Among all the cell types known to date, stem cells provide the best source for augmenting these dysfunctional or dead tissues owing to their intrinsic capability to differentiate into any cell type. Combined with the knowledge of genomics and DNA sequencing, translational stem cell research became not only a reality but it bought a renaissance in regenerative medicine. Like any pioneering technology, this stem cell technology also faced legal, ethical and socio-religious concerns owing to its diverse applications. Human greed and opportunism also crept in which created unnecessary chaos and hype in the sublime and honoured hope which this branch of science had bought into current medicine.

Kommentar

Patent Profiling for Nano Enabled Drug Delivery

Guo Y

Nano Enabled Drug Delivery (NEDD) is widely researched and developed to improve the administration and efficacy of pharmaceutical compounds and molecules. To understand the research situation of NEDD from macro perspectives, we used the patent data to analyze from three aspects and got some interesting results: NEDD was developing steadily, but “safety problems” were becoming big challenges in recent years. NEDD was a highly interdisciplinary emerging field, whose more attractive subsystems were “vector” and “cargo”. One superpower, US, and several strong countries formed the global research pattern. Such “tech mining” offers a systematic perspective on the emerging science or technology under study that is not readily achievable within the individual knowledge of particular researchers.

Forschungsartikel

Effect of Melatonin and Chromium Picolinate Administration to High Carbohydrate Diet-Fed Male Wistar Rats

Doddigarla Z, Parwez I, Abidi S and Ahmad J

Based on the hypothesis that consistent high carbohydrate diet (HCD) can induce insulin resistance (IR), the present study therefore investigated the induction of IR by feeding HCD. Novelty of the study is to evaluate the effects on pancreas, liver, and kidney tissues histology after eight weeks administration of melatonin and chromium picolinate (CrPic) either in single or in combination (melatonin+CrPic) to HCD rats’ respectively. The male Wistar rats were divided into five groups of six rats each. Group I served as control to which normal diet was given, while unlimited HCD was given to group II Group III, IV, and V were also given melatonin, CrPic, and melatonin+CrPic along with HCD in that order. Histopathologic findings of HCD rat pancreatic tissue suggested that the diet altered the normal structure of islets with concomitant lesser cytoplasmic granularity in acinar cells. HCD rat liver showed enlarged hepatocytes with narrowing of sinusoidal spaces. Results revealed after administration of melatonin and CrPic either in single or in combination (melatonin+CrPic) to HCD rats for 8 weeks normalized pancreas and liver alterations when compared with HCD rat pancreas and liver tissues respectively. The present study clearly shows that HCD-fed male Wistar rats that are destined to attain IR and T2DM through diet can be prevented by giving melatonin and CrPic administration in alone or in combination. Promoting this research area through in vitro and in vivo studies will help us to understand melatonin+CrPic mechanistic insights that may ultimately assist clinicians in controlling hyperglycaemia by supplementing as an add-on therapy.

Forschungsartikel

Health Awareness Among Tribes of Rural India

Kankana De

The tribal populations are is recognised as socially and economically vulnerable. Their lifestyles and food habits are different from that of their rural neighbours. They depend on minor forest produce and manual labour for livelihood. They may not have adequate income. Their food consumption pattern is dependent on the vagaries of nature and varies from extreme deprivation (in the lean seasons) to high intakes (in the post-harvest period). About 21% of them are scheduled castes and 24% are tribes. Purulia suffers from very poor conditions in terms of hygiene, poverty, and lack of safe drinking water, resulting in major health problems such as diarrhoea, malaria, filarial, TB, anaemia, and others. Poor child birth and nutrition standards lead to high IMR and MMR. Open defecation, lack of sanitary latrines, poor educational standards for girl children, and poor awareness of HIV/AIDS also compound Purulia's health and development problems. Tribal people are known to have sexual practices that vary from those of mainstream cultures. Less or nothing is known about the prevalence of HIV and AIDS among tribal people in India, except perhaps in some of the tribal states of the North-East of India as these have high prevalence of drug use. HIV and AIDS has become the fourth largest killer worldwide, and in Asian counterpart which is scattering at an alarming rate. In developing countries, it was estimated that at least half of the non-pregnant and two thirds of the pregnant Women are anaemic. Maternal malnutrition which was quite common among the tribal women was also a serious health problem especially for those having numerous pregnancies too closely spaced and reflected the complex socio-economic factors that affected their overall condition.

Forschungsartikel

Clinical Relevance of Molecular Diagnosis in Patients with Congenital Hypothyroidism

Juan Pablo Nicola

Congenital hypothyroidism, defined as the functional deficiency of thyroid hormones present at birth, occurs in approximately 1: 2,000 to 4,000 newborns. Thyroid hormones play an essential role in the maturation of the central nervous system. Congenital hypothyroidism results in severe neurodevelopmental impairment if untreated and, therefore constitutes the most common preventable endocrine cause of irreversible mental retardation. As clinical diagnosis of hypothyroidism in the newborn period is almost always overlooked, newborn screening programs seeking to identify elevated thyrotropin levels at birth are available to detect primary congenital hypothyroidism mainly. Significantly, early onset on levothyroxine replacement therapy virtually abolishes severe intellectual development.

Congenital hypothyroidism is caused by genetic defects occurring at three different levels, including the hypothalamic-pituitary axis, the thyroid gland, and the peripheral tissues. Up to date, 30 monogenic forms of congenital hypothyroidism have been reported in individuals with thyroid dysgenesis, thyroid dyshormonogenesis, central and peripheral hypothyroidism, highlighting the genetic heterogeneity of the disease.

This mini-review summarizes the latest advances in the genetic basis of monogenic forms of congenital hypothyroidism and novel strategies to uncover the molecular etiology of the disease. Moreover, the article provides the current knowledge and future perspectives on the clinical relevance of the molecular diagnosis in patients with congenital hypothyroidism.

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