Wernicke-Korsakoff syndrome as a rare phenotype of sporadic Creutzfeldt-Jakob disease

We reported the case of a patient with Wernicke-Korsakoff syndrome (WKs) as an early clinical manifestation of sporadic Creutzfeld-Jakob disease (sCJD). The 66-year-old female complained of dizziness and imbalance which mostly occurred while walking. A neurological examination revealed a triad of symptoms characteristic for WKs such as gaze paresis, ataxia of limbs and trunk as well as memory disturbances with confabulations. The disturbances increased during the course of the disease, which led to the death of the patient four months after the appearance of the signs. The patient was finally diagnosed with sCJD disease. The most useful ancillary examination results supporting sCJD diagnosis were brain diffusion DWI MRI (diffusion weighted magnetic resonance imaging) and the presence of 14–3-3 protein in CSF (cerebrospinal fluid). Since that manifestation of sCJD is very unique other causes should be taken into consideration while making a final diagnosis.     

Neuroendocrine tumors of gastrointestinal tract in own material

Neuroendocrine tumors are rare gastrointestinal tract disorders, in which diagnosis and treatment are often difficult. The aim of the paper is to present two cases of patients with neuroendocrine tumor of gastrointestinal tract, who underwent surgical procedure in II Department of General and Gastroenterological Surgery of Medical University of Bia?ystok in 2005. A 63-year-old female patient with primary diagnosis of neuroendicrine tumor metastases in liver was not successfully investigated for primary tumor in the preoperative period. The laparotomy procedure indicated the malignant neuroendocrine tumor in the terminal ileum and metastases to the liver and to the greater omentum. The right hemicolectomy and liver metastatic segment VII and VIII resection were performed. The neurological disturbances of obscure origin were observed in the postoperative period and the patient suddenly died on the 15(th) day after surgery. A 57-years-old male patient was operated on for lymph node recurrence of gastric tumor. Pathologic examination of tissue sample revealed the diagnosis of carcinoid. The patient underwent subtotal gastric resection for a pyloric ulcer, diagnosed as Adenocarcinoma G2 pT2N0M0 6 years before. Liver and abdominal node metastases, confirmed by octreoscan, were observed after lymphadenectomy, The treatment of somatostatin analogues (LAR octreotide) was used. In spite of therapy the patient died. The authors present their own experiences and show the preoperative diagnostic difficulties in patients with neuroendocrine gastrointestinal tumors. Unexpected neurological complications in the treatment course were described.     

NUTRITIONAL ASPECTS OF ANASTOMOTIC OPERATIONS—With Special Reference to the Sprue Syndrome

Necessary but radical operation which results in short-circuits between various levels of the digestive tract, with or without resections of portions of the esophagus, stomach or intestine, frequently cures the condition for which the operation was done, but leaves the patient with difficult nutritional problems. These nutritional disturbances are usually associated with inability to maintain or gain weight as a result of badly regulated movement of food material through the altered digestive tract, and by the removal or diversion of important digestive secretions, such as those elaborated by the stomach, pancreas, duodenum and small bowel.Increased intestinal rate and diminished specific gastrointestinal secretions reduce the ability of the small bowel to properly absorb food, with resulting malnutrition, deficiency disease, and at times specific avitaminosis. Inability to absorb fat and fat-soluble substances is a constant feature of these conditions. Successful treatment of the nutritional problems involves constant, prolonged overfeeding of nonbulky foods, usually given in regular, frequently administered meals of small volume. Vitamin concentrates may occasionally be of some temporary assistance but are not needed if a balanced diet is given and may cause undesirable and sometimes dangerous symptoms. The use of supplemental substances, such as liver extract and a wetting agent, such as “Tween 80,” to improve fat absorption have been demonstrated to be of value.The postoperative conditions described are fairly similar to the condition known as sprue, and it is possible that the general principles underlying the treatment of this disease apply to the entire group of post-operative nutritional disturbances alluded to.     

Nutritional aspects of anastomotic operations with special reference to the sprue syndrome

Necessary but radical operation which results in short-circuits between various levels of the digestive tract, with or without resections of portions of the esophagus, stomach or intestine, frequently cures the condition for which the operation was done, but leaves the patient with difficult nutritional problems. These nutritional disturbances are usually associated with inability to maintain or gain weight as a result of badly regulated movement of food material through the altered digestive tract, and by the removal or diversion of important digestive secretions, such as those elaborated by the stomach, pancreas, duodenum and small bowel. Increased intestinal rate and diminished specific gastrointestinal secretions reduce the ability of the small bowel to properly absorb food, with resulting malnutrition, deficiency disease, and at times specific avitaminosis. Inability to absorb fat and fat-soluble substances is a constant feature of these conditions. Successful treatment of the nutritional problems involves constant, prolonged overfeeding of nonbulky foods, usually given in regular, frequently administered meals of small volume. Vitamin concentrates may occasionally be of some temporary assistance but are not needed if a balanced diet is given and may cause undesirable and sometimes dangerous symptoms. The use of supplemental substances, such as liver extract and a wetting agent, such as "Tween 80," to improve fat absorption have been demonstrated to be of value.The postoperative conditions described are fairly similar to the condition known as sprue, and it is possible that the general principles underlying the treatment of this disease apply to the entire group of post-operative nutritional disturbances alluded to.     

New antiemetic drugs

Three major areas of medicine are identified in which there is a need for new antiemetic drugs. These are the nausea and vomiting arising from gastrointestinal motility disturbances (functional dyspepsia, diabetic neuropathy, classical migraine), the sickness evoked by abnormal motion, and the severe emesis experienced by cancer patients as a result of certain cytotoxic therapies. For gastrointestinal-related nausea, selective stimulants of gut motility are suggested to form the basis for a new type of antiemetic therapy. In motion sickness, there has been progress in the understanding of the illness, but little advance in the development of new drugs that selectively prevent this type of sickness. In cancer chemo- and radio-therapy, the discovery that selective 5-HT3 (5-HT, 5-hydroxytryptamine) receptor antagonists can prevent severe cytotoxic-evoked emesis now promises to radically change the type of antiemetic therapy given to these patients. This type of antiemetic compound and the pharmacology of the new 5-HT3 receptor antagonists are, therefore, discussed in detail.     

Cryptosporidium--biotechnological advances in the detection, diagnosis and analysis of genetic variation

Cryptosporidiosis is predominantly a gastrointestinal disease of humans and other animals, caused by various species of protozoan parasites representing the genus Cryptosporidium. This disease, transmitted mainly via the faecal-oral route (in water or food), is of major socioeconomic importance worldwide. The diagnosis and genetic characterization of the different species and population variants (usually recognised as "genotypes" or "subgenotypes") of Cryptosporidium is central to the prevention, surveillance and control of cryptosporidiosis, particularly given that there is presently no broadly applicable treatment regimen for this disease. Although traditional phenotypic techniques have had major limitations in the specific diagnosis of cryptosporidiosis, there have been major advances in the development of molecular analytical and diagnostic tools. This article provides a concise account of Cryptosporidium and cryptosporidiosis, and focuses mainly on recent advances in nucleic acid-based approaches for the diagnosis of cryptosporidiosis and analysis of genetic variation within and among species of Cryptosporidium. These advances represent a significant step toward an improved understanding of the epidemiology as well as the prevention and control of cryptosporidiosis.     

The promise of protein glycosylation for personalised medicine

BackgroundComplex diseases such as cancer are a consequence of numerous causes. State of the art personalised medicine approaches are mostly based on evaluating patients' individual genetic background. Despite the advances of genomics it fails to take individual dynamic influences into account that contribute to the individual and unique glycomic and glycoproteomic “configurations” of every living being.Scope of reviewGlycomic and glycoproteomic-based personalised medicine diagnostics are still in their infancies, however some initial success stories indicate that these fields are highly promising to mediate novel early diagnosis and disease stratification markers, subsequently resulting in improved patient well-being and reduced treatment costs. In this review we not only summarise current protein glycosylation based examples that substantially improve or possess great potential for personalised medicine, but also describe current limitations as well as future perspectives and challenges associated with establishing protein glycosylation aspects for this purpose.Major conclusionsMany protein biomarkers currently in clinical use are glycoproteins, however, their glycosylation status is seldom evaluated in a clinical context. To date just few examples have already been successfully translated into clinical practice, making protein glycosylation a highly promising diagnostic target with humongous potential for personalised medicine.General significanceThere is an urgent need for markers that enable the establishment of an individualised and optimised patient treatment at the earliest disease stage possible. The glycosylation status of a patient and/or specific marker proteins can provide important clues that result in improved patient management. This article is part of a Special Issue entitled “Glycans in personalised medicine” Guest Editor: Professor Gordan Lauc.     

Gene mutation‐based and specific therapies in precision medicine

Precision medicine has been initiated and gains more and more attention from preclinical and clinical scientists. A number of key elements or critical parts in precision medicine have been described and emphasized to establish a systems understanding of precision medicine. The principle of precision medicine is to treat patients on the basis of genetic alterations after gene mutations are identified, although questions and challenges still remain before clinical application. Therapeutic strategies of precision medicine should be considered according to gene mutation, after biological and functional mechanisms of mutated gene expression or epigenetics, or the correspondent protein, are clearly validated. It is time to explore and develop a strategy to target and correct mutated genes by direct elimination, restoration, correction or repair of mutated sequences/genes. Nevertheless, there are still numerous challenges to integrating widespread genomic testing into individual cancer therapies and into decision making for one or another treatment. There are wide‐ranging and complex issues to be solved before precision medicine becomes clinical reality. Thus, the precision medicine can be considered as an extension and part of clinical and translational medicine, a new alternative of clinical therapies and strategies, and have an important impact on disease cures and patient prognoses.     

Roles of microRNAs in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract that mainly affects young people. IBD is associated with various gastrointestinal symptoms, and thus, affects the quality of life of patients. Currently, the pathogenesis of IBD is poorly understood. Although intestinal bacteria and host immune response are thought to be major factors in its pathogenesis, a sufficient explanation of their role in its pathophysiologic mechanism has not been presented. MicroRNAs (miRNAs), which are small RNA molecules that regulate gene expression, have gained attention as they are known to participate in the molecular interactions of IBD. Recent studies have confirmed the important role of miRNAs in targeting certain molecules in signaling pathways that regulate the homeostasis of the intestinal barrier, inflammatory reactions, and autophagy of the intestinal epithelium. Several studies have identified the specific miRNAs associated with IBD from colon tissues or serum samples of IBD patients and have attempted to use them as useful diagnostic biomarkers. Furthermore, some studies have attempted to treat IBD through intracolonic administration of specific miRNAs in the form of nanoparticle. This review summarizes the latest findings on the role of miRNAs in the pathogenesis, diagnosis, and treatment of IBD.     

Genetics,Diagnosis, and Management of Medullary Thyroid Carcinoma and Pheochromocytoma/Paraganglioma

ObjectiveMedullary thyroid carcinoma (MTC) and pheochromocytoma/paraganglioma (PHEO/PGL) are rare neuroendocrine tumors. Because of the increased metastatic rates in certain genetic backgrounds, early diagnosis and treatment are essential to improved patient outcomes. Our objective was to summarize recent findings related to the genetics, diagnosis, and management of MTC and PHEO/PGL.MethodsA literature review was performed.ResultsMTC is primarily associated with mutations in the rearranged during transfection (RET) protooncogene. Determining the specific genetic mutation can guide patient management and screening. Early detection and appropriate surgical management of MTC is critical to prevent or limit metastatic spread, as treatment options for patients with metastatic disease are limited. PHEO/PGL also has a strong genetic component, with approximately 50% of cases linked to germline and somatic mutations in 15 genes. Although most PHEO/PGLs are benign, factors such as genetic background, size, tumor location, and high methoxytyramine levels are associated with higher rates of metastatic disease. The state-of-the-art diagnosis and localization of PHEO/PGLs is based on measurement of plasma metanephrines and methoxytyramine and functional imaging studies. For both PHEO/PGL and MTC, surgery is the only curative treatment. Treatment options for patients with metastatic disease are limited.ConclusionAs genetic testing becomes more widely available, the diagnosis of MTC and PHEO/PGL will be made earlier due to routine screening of at-risk patients. In addition, continued advances in basic science, diagnostic methods, and imaging techniques will improve understanding of the pathogenesis of these diseases and facilitate the introduction of novel treatment strategies for patients with metastatic disease. (Endocr Pract. 2014;20:176-187)     

A recent update on the use of Chinese medicine in the treatment of inflammatory bowel disease

BackgroundInflammatory bowel disease (IBD) is a chronic idiopathic disease that is characterized by inflammation of the gastrointestinal tract. Proper management of IBD requires both early diagnosis and novel therapies and management programs. Many reports have suggested that Chinese medicine has unique properties favorable to the treatment of IBD. However, there are no systematic analyses on this topic.PurposeThis review summarizes recent studies that assessed the effects and mechanisms of Chinese medicine in the treatment of IBD in order to fully understand the advantages of Chinese medicine in the management of IBD.MethodsA literature search was conducted using peer-reviewed and clinical databases, including PubMed, Web of Science, ClinicalTrials.gov, MEDLINE, EMBASE, Springer LINK, Wan-fang database, the Chinese Biomedicine Database, and the China National Knowledge Infrastructure (CNKI). Keywords used were inflammatory bowel disease (including Ulcerative colitis or Crohn's disease) and Chinese medicine. All selected articles were from 1997 to 2021, and each were assessed critically for our exclusion criteria. Studies describing the pathogenesis of IBD, the effects and mechanisms of Chinese medicine in the treatment of IBD, in particular their roles in immune regulation, intestinal flora regulation, and improvement of intestinal barrier function, were included.ConclusionThis review highlights recent progress in the use of Chinese medicine in the treatment of IBD. It also provides a reference for further evaluation and exploration of the potential of classical multi-herbal Chinese medicine in the treatment of IBD.     

Prospects for translational regenerative medicine

Translational medicine is an evolutional concept that encompasses the rapid translation of basic research for use in clinical disease diagnosis, prevention and treatment. It follows the idea "from bench to bedside and back", and hence relies on cooperation between laboratory research and clinical care. In the past decade, translational medicine has received unprecedented attention from scientists and clinicians and its fundamental principles have penetrated throughout biomedicine, offering a sign post that guides modern medical research toward a patient-centered focus. Translational regenerative medicine is still in its infancy, and significant basic research investment has not yet achieved satisfactory clinical outcomes for patients. In particular, there are many challenges associated with the use of cell- and tissue-based products for clinical therapies. This review summarizes the transformation and global progress in translational medicine over the past decade. The current obstacles and opportunities in translational regenerative medicine are outlined in the context of stem cell therapy and tissue engineering for the safe and effective regeneration of functional tissue. This review highlights the requirement for multi-disciplinary and inter-disciplinary cooperation to ensure the development of the best possible regenerative therapies within the shortest timeframe possible for the greatest patient benefit.     

Is infertility a disease and does it matter?

Claims about whether or not infertility is a disease are sometimes invoked to defend or criticize the provision of state‐funded treatment for infertility. In this paper, I suggest that this strategy is problematic. By exploring infertility through key approaches to disease in the philosophy of medicine, I show that there are deep theoretical disagreements regarding what subtypes of infertility qualify as diseases. Given that infertility’s disease status remains unclear, one cannot uncontroversially justify or undermine its claim to medical treatment by claiming that it is or is not a disease. Instead of focusing on disease status, a preferable strategy to approach the debate about state‐funded treatment is to explicitly address the specific ethical considerations raised by infertility. I show how this alternative strategy can be supported by a recent theoretical framework in the philosophy of medicine which avoids the problems associated with the concepts of health and disease.     

Neurochemical approaches of cerebrospinal fluid diagnostics in neurodegenerative diseases

Alzheimer's disease (AD), Parkinson's disease dementia (PDD)/Lewy-body disease (DLB), and frontotemporal dementia (FTD) are the major causes of memory impairment and dementia. As new therapeutic agents are visible for the different diseases, there is an ultimate need for an early and an early differential diagnosis. Since cerebrospinal fluid (CSF) is in direct contact with the central nervous system (CNS), potentially promising biomarkers might be seen there first. In principle, two research approaches can be considered for the laboratory diagnosis of dementias: (i) the direct detection of disease specific protein like Abeta-peptide-oligomers in AD or alpha-synuclein-aggregates in DLB and (ii) the detection of surrogate markers that show an altered pattern of expression in early stages of the disease or are used in the differential diagnosis of other dementias and thus enable an exclusion diagnosis. Especially Abeta-peptides and tau-protein measurements seem to employ a combination of these approaches. Until now it was shown that a combined determination of just these few markers (tau-proteins and Abeta-peptides) is already sufficient to achieve a high degree of diagnostic certainty in the diagnosis of AD. However although these markers seem to correlate with neuropathological changes and memory disturbances, these markers are not specific for a single form of dementia and further research is necessary to improve especially the early differential diagnosis of dementias.     

Tremor, seizures and psychosis as presenting symptoms in a patient with chronic lyme neuroborreliosis (LNB)

Lyme borreliosis is a multisystem disorder caused by Borrelia burgdorferi (Bb). Neurological symptoms such as lymphocytic meningoradiculoneuritis (Bannwart's syndrome), cranial neuritis (II,III,IV,V,VI), encephalitis, transverse myelitis are found in about 10% of cases during the second phase of the disease. In the chronic stage, many months or years after the initial infection, other neurologic complications may occur, such as encephalomyelitis, epileptic crises, cognitive impairment, peripheral neuropathy and psychiatric disturbances such as depression, anxiety, panicc attacks, catatonia, psychosis etc. Some patient continue to experience symptoms of fatigue, insomnia or psychiatric disorder in the post borrelia syndrome. We describe here a patient with a triad of unusual symptoms in chronic LNB including tremor, seizures and psychosis. Standardized medical interview, neurologic examination, neuroimaging, serum and CSF serology as well as EEG and EMNG evaluation were performed. The patient was treated with intravenous ceftriaxone and doxycycline and responded with rapid clinical and functional improvement.Newertheless, he suffered from multiple systemic and neurologic sequelas that influenced his daily activities in post treatment period. Emphasis is placed on the atypical onset and evolution, the difficulties encountered in formulating diagnosis, early treatment and the uncertainties concerning the sequelae after treatment. In patients with non-specific long lasting symptoms in the absence of overt clinical signs suggesting CNS involvement, routine treatment with i.v. ceftriaxone is not to be encouraged.     

Gut feelings: the emerging biology of gut-brain communication

The concept that the gut and the brain are closely connected, and that this interaction plays an important part not only in gastrointestinal function but also in certain feeling states and in intuitive decision making, is deeply rooted in our language. Recent neurobiological insights into this gut-brain crosstalk have revealed a complex, bidirectional communication system that not only ensures the proper maintenance of gastrointestinal homeostasis and digestion but is likely to have multiple effects on affect, motivation and higher cognitive functions, including intuitive decision making. Moreover, disturbances of this system have been implicated in a wide range of disorders, including functional and inflammatory gastrointestinal disorders, obesity and eating disorders.     

Morphological restructuring of the cellular elements of the ventral tegmental area in selective damage to the catecholaminergic systems of the brain

Electron microscopical investigation of the ventral tegmental area at various time after administration of a specific neurotoxin 6-hydroxydopamine made it possible not only to reveal catecholamine reactive elements, but also those structural reorganizations in them, that are dependent on the lesion of the catecholaminergic systems, including certain changes in the receptor apparatus. Dark neurons with the change of different organelles preserve for a long time, up to 2.5 months. Reactive and destructive reorganizations of some axons, terminal buttons and postsynaptic poles of the ventral tegmental area are accompanied with certain functional disturbances, observed both experimentally and at a pathological process. The results of the work demonstrate that under conditions of the model experiments there is a possibility to study various stages of pathogenesis of a number of nervous-psychical diseases, connected or accompanied with disorders in certain mediator systems.     

The use of transfer factors in chronic fatigue syndrome: prospects and problems

Chronic fatigue syndrome (CFS) is a heterogeneous disorder characterized by severe prolonged unexplained fatigue and a variety of associated symptoms such as arthralgias, myalgias, cognitive dysfunction, and severe sleep disturbances. Many patients initially present with an acute onset of apparent infectious origin with either an upper respiratory or gastrointestinal illness, fever, chills, tender lymphadenopathy, and malaise suggestive of a flu-like illness. In some cases, specific viral infections can be identified at the outset, particularly herpes viruses such as Epstein-Barr virus (EBV), human herpes virus-6 (HHV-6), and cytomegalovirus (CMV). Transfer factors (TF) with specific activity against these herpes viruses has been documented. With some studies suggesting that persistent viral activity may play a role in perpetuation of CFS symptoms, there appears to be a rationale for the use of TF in patients with CFS and recent reports have suggested that transfer factor may play a beneficial role in this disorder. This report focuses on the heterogeneity of CFS, the necessity for randomized coded studies, the importance of patient selection and sub-classification in clinical trials, and the need to utilize specific end-points for determining efficacy of treatment.     

重症水痘临床特点分析

目的分析23例重症水痘临床特点。方法收集23例重症水痘患者的临床资料,分析其临床特征。结果重症水痘患者可出现心、肺、肝、脑、肾、胃肠道等多脏器受累表现,这些患者或是机体内存在免疫力低下的各种因素,或是因对疾患缺乏一定认知,从而存在延误就诊或是诊疗不规则,因此出现重症表现。结论提高认知、早期诊断、规范治疗对减低重症水痘发病率及改善预后有重要意义。