Myocardial disarray or disorganisation is at present a contentious topic, not least because its value as a clinical marker for hypertrophic cardiomyopathy has changed considerably over the years. Initially observed as one of the features of asymmetric septal hypertrophy, disarray has since been promoted as its pathognomonic histological feature, regarded by some observers as the morphological manifestation of a genetically transmitted myocardial defect. Recently, however, it has become evident that myocardial disarray is not limited to hypertrophic cardiomyopathy, but is encountered in hearts with both congenital and acquired conditions, and is also observed in normal hearts. The specificity of disarray for hypertrophic cardiomyopathy is thus seriously questioned. Latterly, it has been suggested that disarray, judged from through-and-through sections of the ventricular midseptum is a highly specific and sensitive marker of hypertrophic cardiomyopathy when considered in quantitative rather than qualitative fashion. The present study sets out to answer the question whether disarray could be the histological expression of the normal but intricate fibre architecture of the heart, a consideration also initiated by debatable definitions of normality and abnormality of myocardial histology. Gross fibre dissections in five normal hearts showed that many sites occurred in which disarray was a natural phenomenon. In five more hearts it was found that the plane of section of a tissue block might profoundly influence the histology. In fact...
The paper concerns the rare supratentorial, intracerebral or convexity cysts in adults having a wall lined with an epithelium resembling ependyma. The clincopathological aspects of such cysts are reviewed from 15 published cases and two specimens of the authors which could be examined with the electronmicroscope. These cysts manifest at a median age of 46 years as progressive, space occupying lesions with a fairly rapid clinical course of about one to two years. Twelve of 17 cysts were located in the frontal lobes, most were unequivocally intracerebral and none communicated with the lateral ventricle. Microscopic examination of the cyst wall disclosed some variance in structure, the most common feature being a monolayer of ciliated cells sitting on a very thin collagen membrane. One of the present cases was unique in that the compression by the cyst had caused a shell of infarction in the encompassing tissue. The fine structure of the cysts is described and compared with that of potential host tissues from which such cysts may originate. It is concluded that the cysts arise from displaced segments of the wall of the neural tube which correspond to the sites from which the tela chorioidea forms.
Twenty-seven cases of hydrocephalus associated with aqueduct stenosis are reviewed, and a further nine cases discussed in which hydrocephalus was present and the aqueduct was stenosed but some additional feature was present. This was either a meningocoele or an encephalocoele, or else the aqueduct was not completely obstructed radiologically at the initial examination. The ratio of the peripheral measurement from the inion to the nasion to the distance between the inion and the posterior lip of the foramen magnum is presented for each case with an outline of the ventricles. The cases behave as would be expected if the aqueduct was being blocked by the lateral compression of the mid-brain between the enlarged lateral ventricles. On reviewing these cases and other evidence it is suggested that non-tumourous aqueduct stenosis is more likely to be the result of hydrocephalus than the initial cause. The response to treatment is reviewed and a high relapse rate noted. It is suggested that assessment of the extracerebral pathways may be advisable before undertaking third ventriculostomy or ventriculo-cisternostomy.
Cardiac amyloidosis is caused by amyloid deposits derived from different human plasma proteins. It can lead to cardiac conduction disturbances, restrictive cardiomyopathy, and low output heart failure. The heart is variably involved during the development of systemic amyloidosis and seems to be more frequently affected in immunoglobulin (primary) than in reactive (secondary) amyloidosis. Amyloid is common in the elderly. Isolated atrial amyloid, for which a major subunit is the atrial natriuretic peptide, seems to be three times more frequent than senile cardiac amyloid, which is derived from normal prealbumin (transthyretin). Like polyneuropathy, cardiac amyloidosis is a prominent clinical feature of hereditary amyloidosis, namely of the autosomal dominant transthyretin (TTR) type. All 28 cases of TTR amyloidoses reported so far were heterozygotes for a single nucleotide change in the gene for TTR that resulted in amino acid substitutions in the mature protein. A new TTR genetic variant is reported in a German family where the index patient presented at the age of 63 with anginal pain and arrhythmia. Electrocardiography was suggestive of a pseudoinfarction pattern, and echocardiography and cardiac catheterisation showed signs of hypertrophic nonobstructive cardiomyopathy with increased ventricular filling pressures and a prominent "a" wave. Amyloid of the TTR type was identified by immunohistochemistry in the endomyocardial biopsy specimen. Hybrid isoelectric focusing established heterozygosity by showing normal TTR protein and an electrically neutral TTR variant differing from all known TTR variants so far. The patient died in an accident before investigations were complete. Electrophoretic analysis of the plasma from his first degree relatives (son...
A selective subtotal cerebellar neuronal degeneration was found in a patient who died 4 1/2 months after suffering neuroleptic malignant syndrome (NMS), a rare, potentially fatal disorder associated with neuroleptic medications. It is suggested that the cerebellar neuronal degeneration in this case was due to hyperpyrexia, a cardinal clinical feature of NMS. Similar pathologic findings appear not to have been previously reported in NMS but have been described in heat-induced central nervous system (CNS) injury. The findings imply that a cerebellar syndrome might be encountered in patients who survive NMS complicated by a particularly high febrile course.
This survey reviews the diagnosis (predominantly radiological) of 32 cases of pseudoachondroplasia from 26 kindreds and illustrates the natural history and varying appearance of the disordered bone growth from infancy to adult life. In addition, an attempt has been made to detect phenotypic differences between autosomal dominant and recessive types (excluding isolated cases), analysing 10 kindreds of dominant inheritance (three in the current survey, seven from published reports) and six of recessive inheritance (three in the current survey, three from published reports). There appears to be no clinical or radiographical feature which clearly distinguishes them, but, using height as a criterion of severity, among those with autosomal recessive inheritance there was a disproportionate number of the most severely affected cases and there also appears to be very little intrafamilial variation. It is possible that pseudoachondroplasia can be subdivided into autosomal dominant mild and severe and autosomal recessive mild and severe, but full delineation must await elucidation of the basic defect at biochemical and molecular levels.
Granuloma inguinale (donovanosis) is commonly thought to be a superficial disease, which spreads by continuity and does not affect the regional lymph nodes. Two patients with the disease affecting lymph nodes in the neck are reported from a series of 108 seen in a continuing study of granuloma inguinale. An immunofluorescent antibody test is described that showed antigenic relatedness between the intracellular organisms in these patients and in patients with typical genital granuloma inguinale. Lymphadenitis associated with granuloma inguinale appears to be a stage in the pathogenesis of the pseudobubo, an uncommon feature of this disease.
Summary: Neuropathic pain might best be considered as a collection of various pain states with a common feature, that being symptoms suggestive of dysfunction of peripheral nerves. The development of therapeutic options for the treatment of neuropathic pain is complicated significantly by several factors. Neuropathic pain may arise from widely diverse etiologies such as physical trauma, disease, infection, or chemotherapy. Symptoms indicative of neuropathic pain may also arise in individuals with no evidence of any type of nerve trauma (idiopathic). Although neuropathic pain is a substantial health care issue, it is relatively uncommon and only occurs in a small fraction (<10%) of individuals with these initiating factors. Moreover, the efficacy of treatment protocols, even against the same type of symptoms, differ depending on the underlying initiating cause of the neuropathy. Although these observations strongly suggest that there are predisposing factors that may impart susceptibility to the development of neuropathic pain, no common predisposing factors or genetic markers have been satisfactorily identified. Because of these vagaries, treatment of neuropathic pain has been based on trial and error. However, recent progress in the understanding of neurophysiologic changes that accompany peripheral nerve dysfunction indicate that regulation of ion channels that maintain membrane potentials or generate action potentials may provide an important therapeutic approach. Neuropathic pain is accompanied by increased activity of peripheral nociceptors...
Abdominal involvement in brucellosis is seen in the acute, subacute and chronic disease. It is not typical, however, that acute abdomen is the presenting feature of brucellosis. In this paper, two cases of serologically diagnosed brucellosis are reported, both presenting initially with acute abdomen and fever. In brucella-endemic regions of the world, brucellosis has to be considered in the differential diagnosis of acute abdomen and fever. With definitive diagnosis, unnecessary laparotomy can be avoided.
A 14 year old girl with multiseptate gall bladder and cystic dilatation of the biliary tree is presented. This is the 20th published case report of patients with multiseptate gall bladder and only the second to be associated with a choledochal cyst. The cystic spaces of the gall bladder did not communicate with the neck of the gall bladder or the rest of the biliary tree, and this unusual feature has not been previously described. A multiseptate gall bladder with a normal biliary tree commonly causes symptoms suggestive of cholecystitis, although gall stones are seldom present. Diagnosis is confirmed by an oral cholecystogram or ultrasound scan that may show the fine intraluminal septae, and these features should be looked for in patients with biliary symptoms without biliary calculi. Cholecystectomy is curative for the isolated gall bladder anomaly but hepaticojejunostomy may be necessary for an associated choledochal cyst.
In Nature, directional surfaces on insect cuticle, animal fur, bird feathers, and plant leaves are comprised of dual micro-nanoscale features that tune roughness and surface energy. This feature article summarizes experimental and theoretical approaches for the design, synthesis and characterization of new bioinspired surfaces demonstrating unidirectional surface properties. The experimental approaches focus on bottom-up and top-down synthesis methods of unidirectional micro- and nanoscale films to explore and characterize their anomalous features. The theoretical component of the review focuses on computational tools to predict the physicochemical properties of unidirectional surfaces.
Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by
repeated episodes of dream enactment behavior and REM sleep without atonia (RSWA) during
polysomnography recording. RSWA is characterized by increased phasic or tonic muscle activity seen
on polysomnographic electromyogram channels. RSWA is a requisite diagnostic feature of RBD, but may
also be seen in patients without clinical symptoms or signs of dream enactment as an incidental
finding in neurologically normal individuals, especially in patients receiving antidepressant
therapy. RBD may be idiopathic or symptomatic. Patients with idiopathic RBD often later develop
other neurological features including parkinsonism, orthostatic hypotension, anosmia, or cognitive
impairment. RSWA without clinical symptoms as well as clinically overt RBD also often occurs
concomitantly with the α-synucleinopathy family of neurodegenerative disorders, which
includes idiopathic Parkinson disease, Lewy body dementia, and multiple system atrophy. This review
article considers the epidemiology of RBD, clinical and polysomnographic diagnostic standards for
both RBD and RSWA, previously reported associations of RSWA and RBD with neurodegenerative disorders
and other potential causes...
A unique feature of N-methyl-D-aspartate receptors (NMDARs) that distinguishes them from other ionic receptors is that their activation requires more than one agonist to bind simultaneously to distinct binding sites on the receptor. D-serine, a co-agonist binding to the glycine site of NMDARs, has been implicated in several NMDAR-dependent physiological processes, and altered D-serine levels under certain pathophysiological conditions contribute to neural dysfunction via NMDARs in the central nervous system. Entry of HIV-1 in the brain causes neuronal injury leading to cognitive, behavioral and motor impairments known as HIV-associated neurocognitive disorders (HAND). As HIV-1 does not infect neurons, neuronal injury is believed to be primarily mediated by an indirect mechanism,that is, HIV-1-infected and/or immune-activated macrophages and microglial cells release soluble molecules leading to neuronal injury or death. Among the soluble factors is D-serine. In this article we try to address recent progresses on the role D-serine might play in the pathogenesis of neurodegenerative disorders with a particular emphasis of the involvement of D-serine in HIV-1-associated neurotoxicity.
Xenotransplantion remains the most viable option for significant expansion of the donor organ pool in clinical transplantation. With the advent of nuclear transfer technologies, the production of transgenic swine has become a possibility. These animals have allowed transplant investigators to overcome humoral mechanisms of hyper-acute xenograft rejection in experimental pig-to-non-human primate models. However, other immunologic barriers preclude long-term acceptance of xenografts. This review article focuses on a major feature of xenogeneic rejection: xenogeneic T cell responses. Evidence obtained from both small and large animal models, particularly those using either islet cells or kidneys, have demonstrated that T cell responses play a major role in xenogeneic rejection, and that immunosuppression alone is likely incapable of completely suppressing these responses. Additionally, both the direct and indirect pathway of antigen presentation appear to be involved in these anti donor processes. Enhanced understanding of (i) CD47 and its role in transduced xeno-bone marrow (ii) CD39 and its role in coagulation dysregulation and (iii) thymic transplantation have provided us with encouraging results. Presently, experiments evaluating the possibility of xenogeneic tolerance are underway.
The relative simplicity of plant developmental systems, having evolved within the universal constraints imposed by the plant cell wall, may allow us to outline a consistent developmental narrative that is not currently possible in the animal kingdom. In this article, I discuss three aspects of the development of the mature form in plants, approaching them in terms of the role played by the biophysics and mechanics of the cell wall during growth. First, I discuss axis extension in terms of a loss of stability-based model of cell wall stress relaxation and I introduce the possibility that cell wall stress relaxation can be modeled as a binary switch. Second, I consider meristem shape and surface conformation as a controlling element in the morphogenetic circuitry of plant organogenesis at the apex. Third, I approach the issue of reproductive differentiation and propose that the multicellular sporangium, a universal feature of land plants, acts as a stress–mechanical lens, focusing growth-induced stresses to create a geometrically precise mechanical singularity that can serve as an inducing developmental signal triggering the initiation of reproductive differentiation. Lastly, I offer these three examples of biophysically integrated control processes as entry points into a narrative that provides an independent...
Over the last decade there has been a considerable effort directed toward reformulating the standard approach taken to preclinically model stroke and stroke recovery. The principal objective of this undertaking has been to improve the success with which preclinical findings can be translated. Although several advancements have already been introduced, one potentially critical feature that appears to have been overlooked is psychological stress. Stroke is well recognized to produce high levels of stress in patients, and ongoing exposure to stress is recognized to deleteriously interfere with recovery. The presence of high levels of stress (distress) in stroke patients is also relevant because nearly all clinically deployed neurorestorative interventions occur against this background. Somewhat perplexingly, however, we could find no preclinical stroke studies concerned with investigating the efficacy of putative neurorestorative compounds that did so in the presence of stress. The following article will make the case that failure to recognize or compensate for the effects of ongoing stress in standard preclinical experimental models of recovery is likely to result in overestimation of the effectiveness of pharmacological or behavioral neurorestorative interventions.
Prostate cancer (CaP) is the most commonly diagnosed malignancy in males in the Western world with one in six males diagnosed in their lifetime. Current clinical prognostication groupings use pathologic Gleason score, pre-treatment prostatic-specific antigen and Union for International Cancer Control-TNM staging to place patients with localized CaP into low-, intermediate- and high-risk categories. These categories represent an increasing risk of biochemical failure and CaP-specific mortality rates, they also reflect the need for increasing treatment intensity and justification for increased side effects. In this article, we point out that 30–50% of patients will still fail image-guided radiotherapy or surgery despite the judicious use of clinical risk categories owing to interpatient heterogeneity in treatment response. To improve treatment individualization, better predictors of prognosis and radiotherapy treatment response are needed to triage patients to bespoke and intensified CaP treatment protocols. These should include the use of pre-treatment genomic tests based on DNA or RNA indices and/or assays that reflect cancer metabolism, such as hypoxia assays, to define patient-specific CaP progression and aggression. More importantly...
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an uncommon extranodal non-Hodgkin lymphoma, with an aggressive course with no well-defined treatment. This article describes a 56-year-old man, treated surgically 7 months earlier for a subcutaneous nodosity near the left axilla, presenting with a progressive inflamed wound, pain, and high fever (39°C). Treatment with systemic antibiotics and topical anti-inflammatory dressings failed. After 7 months, the patient was diagnosed with SPTCL based on biopsy results and a multidisciplinary consultation. While undergoing systemic chemotherapy with corticosteroid therapy, his wound become more painful, larger, and covered with necrotic tissue. Fifty days after chemotherapy with corticosteroid therapy, his wound became seriously painful and increasingly necrotic. He developed a serious stomachache and abdominal distension, rapidly became comatose, and died. The aim of this case report is to present our experience of the different clinical signs of SPTCL to expedite its early diagnosis in future. We summarize the main clinical characteristics of SPTCL as a rapidly progressing and increasingly painful wound with necrotic tissue, involving a multisystem disorder, which is easily misdiagnosed...
This article looks at the issues of excessive daytime sleepiness and unintended sleep episodes in patients with Parkinson’s disease (PD) and explores the reasons why patients might suffer from these symptoms, and what steps could be taken to manage them. During the last decade, understanding of sleep/wake regulation has increased. Several brainstem nuclei and their communication pathways in the ascending arousing system through the hypothalamus and thalamus to the cortex play key roles in sleep disorders. Insomnia is the most common sleep disorder in PD patients, and excessive daytime sleepiness is also common. Excessive daytime sleepiness affects up to 50% of PD patients and a growing body of research has established this sleep disturbance as a marker of preclinical and premotor PD. It is a frequent and highly persistent feature in PD, with multifactorial underlying pathophysiology. Both age and disease-related disturbances of sleep-wake regulation contribute to hypersomnia in PD. Treatment with dopamine agonists also contribute to excessive daytime sleepiness. Effective management of sleep disturbances and excessive daytime sleepiness can greatly improve the quality of life for patients with PD.
Body packing represents the concealment of illegal substances in a person's body with the aim of smuggling. “Body packers” either swallow drug-filled packets or introduce drug-filled packets into their bodies rectally or vaginally with the purpose of concealing them. The three main smuggled drugs are cocaine, heroin and cannabis products. Body packing represents a serious risk of acute narcotic toxicity from drug exposure, intestinal obstruction owing to pellet impaction and bowel perforation with consequent abdominal sepsis. A suspected body packer is generally admitted to hospital to perform imaging investigations and confirm the presence of drugs in his/her body. Radiological imaging methods are essential to diagnose body packing and to detect potential complications. Increasing sophistication of traffickers and improvements in packaging add to the detection difficulty. Radiologists should be aware of the appearance of drug packets in a range of imaging modalities. This article informs physicians about the challenging aspects of body packing, its background and medicolegal issues, what imaging methods can be used and what criteria are necessary to perform a correct diagnosis.