Polyglandular autoimmune syndrome: current concepts.

The polyglandular autoimmune syndrome (PGAS) is characterized by the association of two or more endocrine disorders that are mediated by autoimmune mechanisms and usually lead to a hypofunctional state. In this review we classify the various types of PGAS and discuss their clinical features and the pathophysiologic autoimmune mechanisms that are thought to play an important role. Circulating organ- and cell-specific autoantibodies are frequently detected in patients with the syndrome and may be a marker of future organ failure. PGAS should be considered in patients with one or more of the disorders constituting the syndrome; this should facilitate early diagnosis and perhaps even prevention of other components of the disease. Early recognition and replacement therapy can be life-saving, particularly when there is adrenal or thyroid insufficiency.     

Postviral fatigue syndrome: time for a new approach

Controversial views on the postviral fatigue syndrome (“myalgic encephalomyelitis”) were critically appraised in their historical context and recent advances in research (virology, immunology, neurophysiology, histopathology, and epidemiology) reviewed. Flaws detected in certain aspects of recent research included in particular failure to define fatigue, inadequate assessment of psychological features, and absent or inappropriate control groups. The findings suggest that the fruitless dichotomy of “organic versus functional” should be replaced by a multifactorial approach. Most important, epidemiological studies with explicit operational case definition are essential before progress can be made in the management of this distressing disorder.     

婴儿期Klippel-Trenaunay综合征并精神运动发育迟缓病例报道及文献复习

Klippel-Trenaunay综合征(KTS)又称先天性静脉畸形骨肥大综合征,好发于儿童及青少年。临床以多发性皮肤血管瘤、肢体静脉曲张、骨及软组织肥大为特征。其病因尚不清楚,可能为遗传性血管壁间质组织发育异常所致。目前尚无特异的治疗方法,手术及介入治疗主要是减轻症状和治疗并发症。对于婴儿期出现偏侧肢体肥大并血管瘤的患儿应长期随访,早期诊断,早期干预以防止并发症。近年来有报道利用超声进行产前诊断,对及时发现和处理有重要意义。本文报道1例婴儿期KTS,以口腔黏膜血管瘤伴出血、颜面及肢体不对称性肥大为特点,并伴精神运动发育迟缓,CT见侧脑室、三脑室扩张。     

Update on the molecular genetics of vascular anomalies

Genetic factors play a critical role in the pathogenesis of vascular anomalies. Significant advances have been made in recent years in identifying the genetic and molecular determinants of a variety of vascular anomalies using a molecular genetic approach. Several genes for vascular anomalies have been identified. These genes include AGGF1 for Klippel-Trenaunay syndrome, RASA1 for capillary malformations, KRIT1, MGC4607, PDCD10 for cerebral cavernous malformations, glomulin for glomuvenous malformations, TIE2 for multiple cutaneous and mucosal venous malformations, VEGFR-3, FOXC2, NEMO, SOX18 for lymphedema or related syndromes, ENG, ACVRLK1, MADH4 for HHT or related syndromes, NDP for Coats' disease, Notch3 for CADASIL, and PTEN for Proteus Syndrome. These findings have made genetic testing possible in some clinical cases, and may lead to the development of therapeutic strategies for vascular anomalies. Furthermore, these studies have identified critical genes involved in vascular morphogenesis, and provided fundamental understanding of the molecular mechanisms underlying vasculogenesis and angiogenesis.     

Hemorrhagic fever with renal syndrome associated with acute pancreatitis

Hemorrhagic fever with renal syndrome (HFRS) is a systemic infectious disease caused by Hantaviruses and characterized by fevers,bleeding tendencies,gastrointestinal symptoms and renal failure.It encom...     

Preliminary Study of a Self-Administered Treatment for Irritable Bowel Syndrome: Comparison to a Wait List Control Group

Despite the accumulation of efficacy data for cognitive-behavioral treatment of Irritable Bowel Syndrome (IBS), efforts to investigate methods for increasing access to psychological treatments are in their infancy. The current study examined the efficacy of self-administered treatment in comparison to a wait list control. Twenty-eight participants monitored gastrointestinal (GI) symptoms and completed measures of quality of life (QOL) and psychological distress prior to randomized assignment to self-help treatment or wait list. Wait listed participants later received treatment. A 3 month post-treatment follow-up was included. Seven participants completed immediate treatment; nine the wait list. The self-help treatment significantly decreased composite GI symptom scores in comparison to the wait list, but did not lead to significant improvements in QOL or distress. In the entire treated sample, including wait list crossovers, analyses showed significant improvement in abdominal pain, average GI symptoms, and perceived health and well-being. Interpretation of these results should be considered in the context of several limitations, including small sample size, brief baseline symptom monitoring, and high drop out rate. Despite these limitations, this study is an important first step in empirically validating low-cost, self-administered treatments as a first line psychological intervention for IBS.     

Early Endoscopy of Oesophagus,Stomach, and Duodenal Bulb in Patients with Haematemesis and Melaena

Oesophago-gastro-duodenoscopy was successfully performed in 196 of 208 patients admitted with haematemesis or melaena, or both. A precise visual diagnosis was made in 80% of all patients and in 96% of those where the final diagnosis lay within the oesophagus, stomach, and first two parts of the duodenum. Bleeding oesophagitis was more common and bleeding duodenal ulcer less common than in other series using mainly radiology. Altogether, 26% of all patients with endoscopically-proved duodenal ulcers were bleeding from another site, and 15·4% of all patients had more than one lesion. This fact, and inability to detect surface lesions limits the value of acute barium radiology, which was performed in only 81 patients. Accurate diagnosis should lead to better understanding of individual lesions and more rational management of individual patients. Where a good service is available oesophago-gastro-duodenoscopy should be performed on all bleeding patients within 24 hours of admission.     

When enough is enough: genetic diseases associated with transcriptional derepression

For many human genetic diseases, the underlying genetic defect has been determined. Thus, although traditionally a field only for researchers in medicine or human genetics, human diseases are now opening up to molecular biologists, cell biologists and biochemists. Here we discuss four human genetic disorders, Familial Alzheimer's disease, Rett syndrome, Klippel-Trenaunay syndrome and Facioscapulohumeral muscular dystrophy, and how investigations into these diseases are providing important lessons about human biology.     

Emergent effects of multiple predators on prey survival: the importance of depletion and the functional response

The combined effects of multiple predators often cannot be predicted from their independent effects. Emergent multiple predator effects (MPEs) include risk enhancement, where combined predators kill more prey than predicted by their individual effects, and risk reduction, where fewer prey are killed than predicted. Current methods for detecting MPEs are biased because they assume linear functional responses and/or no prey depletion. As a result, past studies overestimated the occurrence of risk enhancement for additive designs, and tended to overestimate the occurrence of risk reduction for substitutive designs. Characterising the predators' functional responses and accounting for prey depletion reduces biases in detection, estimation, interpretation and generalisation of the emergent effects of predator diversity on prey survival. These findings have implications beyond MPE's and should be considered in all studies aimed at understanding how multiple factors combine when demographic rates are density dependent.     

Extended use of sodium tetradecyl sulfate in treatment of hemangiomas and other related conditions

Sodium tetradecyl sulfate, a sclerosing agent, has been used in 18 patients in the treatment of difficult hemangiomas not amenable to surgery alone, with or without adjunctive operation, in eyelid and lip lesions, in saccular and large posterior and hypopharyngeal hemangiomas, in Klippel-Trenaunay syndrome, in variceal bleeding around a Koch ileal pouch, and as an adjunct to selective embolization in a patient with a facial A-V malformation. Sodium tetradecyl sulfate was injected intralesionally in aliquots of 0.05 to 0.1 cc at multiple sites in total doses not exceeding 2.0 to 4.0 cc. Two patients showed questionable or no improvement. The remaining 16 patients experienced modest to striking improvement with only very minimal complications in the form of superficial desquamation of skin. The conclusion is, therefore, that sodium tetradecyl sulfate, used appropriately, is a safe and frequently effective agent in the treatment of hemangiomas and a number of similar or related problems. Clinical results will be presented.     

Clinical Profile of Ectopic Thyroid in Asian Indians: a Single-Center Experience

ObjectiveTo assess clinical characteristics of patients with ectopic thyroid seen at a single tertiary care center in India.MethodsIn this case series, we retrospectively reviewed the data of patients who presented with ectopic thyroid between January 1995 and March 2008. Clinical presentation, nuclear imaging findings, endocrine profile, and clinical management were analyzed.ResultsRecords of 22 female patients and 14 male patients were reviewed. Ectopic thyroid was more common in female patients. Mean age of presentation was 14.3 years (median, 14 years; range, 5 months to 40 years). Seventeen patients (47%) presented with lingual thyroid, detected incidentally or because of dysphagia and bleeding while eating, and 19 patients (53%) had sublingual thyroid, which mainly presented as an anterior neck swelling. Thirty patients (83%) had hypothyroidism (overt or subclinical). In 29 patients (81%), ectopic thyroid either in the neck or in the lingual area was the only functional thyroid tissue. Thirty-one patients (86%) were treated medically, and surgery was performed in only 5 patients (14%) who had either recurrent bleeding or dysphagia.ConclusionsEctopic thyroid should be considered during the evaluation of a midline neck mass or hypothyroidism. Careful clinical examination, thyroid function tests, and radionuclide imaging help establish the diagnosis and localize ectopic thyroid. Appropriate treatment should be decided on an individual basis. (Endocr Pract. 2009;15:322-325)     

The Industrial Ecology of Lead and Electric Vehicles

The lead battery has the potential to become one of the first examples of a hazardous product managed in an environmentally acceptable fashion. The tools of industrial ecology are helpful in identifying the key criteria that an ideal lead-battery recycling system must meet maximal recovery of batteries after use, minimal export of used batteries to countries where environmental controls are weak, minimal impact on the health of communities near lead-processing facilities, and maximal worker protection from lead exposure in these facilities. A well-known risk analysis of electric vehicles is misguided, because it treats lead batteries and lead additives in gasoline on the same footing and implies that the lead battery should be abandoned. The use of lead additives in gasoline is a dissipative use where emissions cannot be confined: the goal of management should be and has been to phase out this use. The use of lead in batteries is a recyclable use, because the lead remains confined during cycles of discharge and recharge. Here, the goal should be clean recycling. The likelihood that the lead battery will provide peaking power for several kinds of hybrid vehicles-a role only recently identified increases the importance of understanding the levels of performance achieved and achievable in battery recycling. A management system closely approaching clean recycling should be achievable.     

Counteracting clotting in sepsis

The complexity of factors that regulate bleeding and coagulation has long confounded researchers. Andrew Wei and Shaun Jackson help clear the air by examining clinical findings pointing to a mechanistic basis for a common bleeding disorder, immune thrombocytopenic purpura. Mark Kahn tackles two research studies that could lead to improved therapies for a coagulation syndrome that hits people with severe sepsis.     

Quantitative analysis of the structure of the varicose dilatations in the nerve fibers of the rabbit coronary artery (according to the results of three-dimensional reconstruction)]

Axoplasmic vesicles and microtubes in varicosities of axonal plexus in the external sheath of the rabbit coronary artery have been studied. Comparing serial sections and examining three-dimensional reconstruction of small nerve plexus, it was demonstrated that various varicosities differed only in their correlation of the amount of small (30-80 nm) and large (80-180 nm) vesicles. Average diameters in profiles of small and large vesicles are 56.3 nm and 115.6 nm, respectively. There are varicosities containing about 250 or more than 1,000 vesicles. Evenly distributed vesicles throughout the volume of varicosities and lack of specialized structures on the axolemma are supposed to demonstrate the absence of special areas for the mediator removal in the axons studied. The microtubes in the varicosities are peripherally arranged, next to the axolemma and form 1-1.5 wide coils. A suggestion is made that the varicosities in neighbouring axons of the same nerve plexus, with specific structural organization, are special functional units and appear to be peculiar not only for nerve plexus of the coronary artery, but also for other parts of the peripheral vegetative nerve system.     

Advisory Committee on Dangerous Pathogens (ACDP) Seminar on Microbiological Risk Assessment, 28 January 1997

Microbiological risk assessment is an area of growing importance and significant potential, where the underlying science, software systems and databases are developing to the point of real and useful application. It is also an area where the developing science is posing as many questions as it is presenting answers. Key issues emerging from the day included: the need for more sophisticated management of uncertainty, which is much more relevant to microbiological risk analysis than to other applications; the need for global surveillance systems with better compatibility and appropriate peer review; considered assessment of the impact of new molecular-based diagnostic and screening techniques; the explosion of relevant information available, particularly on the Internet, which makes computer literacy essential both to professionals and 'laymen'; and the appearance of software systems which are either tailored for microbiological application or have the potential for this use. The closely associated issues of risk communication and perception also emerged as being vital to the effective application of microbiological risk management to public health issues. Overall, the majority of participants considered the event to have been valuable and stimulating and thought that it would lead to improvements in the use of microbiological risk assessment. The Advisory Committee on Dangerous Pathogens is committed to taking this topic forward and will be both taking up the messages from this seminar and encouraging development of suitable databases and software systems.     

Incidental findings in neuroimaging research: a framework for anticipating the next frontier

While strategies for handling unusual and possibly clinically significant anatomical findings on brain scans of research volunteers have been developed and implemented across neuroimaging laboratories worldwide, few concrete steps have been taken to consider the next frontier: functional anomalies. Drawing on the genetics literature, early work in neuroimaging considered actionability to be a driving force for determining if and when findings should be disclosed to individuals in whom they are detected, as inherent uncertainty raises potential ethical dilemmas of misdiagnosing and mislabelling people as patients. Here we consider the possibility of incidental findings in brain function during the resting state. Our approach does not anchor the resting state as the sine qua non of functional incidental findings, but as a path to thinking about where they may emerge in the future and how our professional communities need to think about thinking about them. We suggest that considering the issues proactively today, within a framework that is maximally flexible and open to modification, is better than responding reactively after the fact and with no framework at all. We argue that there is a duty to consider possible incidental findings despite the ambiguities of data interpretation, while working hard to prevent unnecessary alarm.     

Light- and electron-microscopic study of synaptic connections in the paracervical ganglion of the female rat: special reference to calcitonin gene-related peptide-, galanin- and tachykinin (substance P and neurokinin A)-immunoreactive nerve fibers and terminals

Nerve fibers and varicosities in the pelvic paracervical ganglia (PG) are immunoreactive for the neuropeptides calcitonin gene-related peptide, galanin, and the tachykinins substance P and neurokinin A. Many of these fibers and varicosities are capsaicin-sensitive, originate in dorsal root ganglia and, thus, are considered to be primary afferent fibers. Numerous immunoreactive varicosities are pericellular to principal neurons in the PG. The present study examines the ultrastructure of calcitonin gene-related peptide-, galanin-, substance P-, and neurokinin A-immunoreactive nerve fibers and varicosities in the ganglia to determine their relationships to principal neurons and their synaptic connectivity. Paracervical ganglia of female rats were processed for light-microscopic immunohistochemistry using antisera against synapsin I, as a nerve terminal marker, and microtubule-associated protein-2 to define soma and dendrites. The rationale for performing this co-immunohistochemical analysis was to reveal the relationship between nerve endings and principal neurons. Synapsin I endings were predominantly axosomatic with fewer being axodendritic. Other ganglia were processed for electron-microscopic immunohistochemistry using both standard immunogold and peroxidase-anti-peroxidase procedures. Unmyelinated fibers and varicosities immunoreactive for calcitonin gene-related peptide, galanin, and the tachykinins were routinely observed in the interstitium between neuron somas. Numerous immunoreactive axon profiles were present in small groups that were ensheathed by Schwann cells. Immunoreactive fibers and varicosities were also observed within the satellite-cell sheath of the neuron soma and often intimately associated with the membrane of the soma, somal protrusions, or with the proximal part of a dendrite. Membrane specializations, indicative of synaptic contacts, between the fibers and the principal neurons were observed. It is suggested that these peptide-immunoreactive sensory fibers and varicosities are involved in regulation of activity in the PG.     

Functional uterine bleeding; etiologic factors and therapy

Endometrial hyperplasia and irregular shedding of the endometrium comprise the largest group of known causes of functional uterine bleeding.Most patients with functional uterine bleeding have a normal endometrial pattern. In a series of patients with functional uterine bleeding, it was noted that 69.7 per cent of endometrial specimens reported as normal showed evidence of hyalinized tissue which included endometrial glands. Tissue of this type was noted in only 3.5 per cent of curetted specimens from patients without functional uterine bleeding. Diagnostic uterine curettage is the initial step in the management of functional uterine bleeding. Hysterectomy and radiation castration are seldom necessary in the management of functional uterine bleeding and are indicated only under specific circumstances.     

Absence of functional peroxisomes does not lead to deficiency of enzymes involved in cholesterol biosynthesis.

To unravel the conflicting data concerning the dependence of human cholesterol biosynthesis on functional peroxisomes, we determined activities and levels of selected enzymes involved in cholesterol biosynthesis in livers of PEX5 knockout mice, a well-characterized model for human Zellweger syndrome. We found that all enzymes measured, including putative peroxisomal enzymes, are at least as active in the peroxisome-deficient Zellweger mice as in control mice, indicating that mislocalization of enzymes to the cytosol does not lead to decreased activity or degradation. Prompted by these results, we re-examined this aspect in human subjects by specific enzyme activity measurements and immunoblotting with highly specific antisera. Our results show that the previously reported deficiencies of mevalonate kinase and phosphomevalonate kinase activity in livers from human Zellweger patients reflect the bad condition of the livers, rather than mislocalization to the cytosol.Our data provide an explanation for the conflicting findings in the literature and show that great care should be taken in the interpretation of data obtained in postmortem material.     

Psychological stress and fibromyalgia: a review of the evidence suggesting a neuroendocrine link

The present review attempts to reconcile the dichotomy that exists in the literature in relation to fibromyalgia, in that it is considered either a somatic response to psychological stress or a distinct organically based syndrome. Specifically, the hypothesis explored is that the link between chronic stress and the subsequent development of fibromyalgia can be explained by one or more abnormalities in neuroendocrine function. There are several such abnormalities recognised that both occur as a result of chronic stress and are observed in fibromyalgia. Whether such abnormalities have an aetiologic role remains uncertain but should be testable by well-designed prospective studies.