Two siblings with an unusual nasal malformation: further instances of craniorhiny?

We report a brother and sister born to consanguineous parents. The siblings have hypertelorism, bifid nose, upturned nares, histologically proven intranasal dermoid, and soft-tissue swellings of the philtrum. One sibling also has a midline cleft lip and the other has narrowing of the posterior choanae. We suggest that they have craniorhiny, despite the absence of an abnormal skull shape. The differential diagnosis is discussed.     

Hyperplastic-like mucosal change in Crohn's disease: an unusual form of dysplasia?

Patients with Crohn's disease are at increased risk of developing intestinal adenocarcinoma. Dysplasia is both a marker and a precursor of adenocarcinoma in this setting. In a review of our cases of Crohn's-related adenocarcinoma, we noted a peculiar hyperplastic-like mucosal change (HPC) in mucosa both adjacent to and distant from the adenocarcinoma in some cases. However, the significance of this change is unknown. We evaluated 30 cases of Crohn's-related adenocarcinoma and 30 age- and site-matched resection specimens with Crohn's disease without adenocarcinoma to determine the prevalence of this mucosal alteration in these groups. HPC was recognized by a diffuse expanse of flat mucosa with an architecture resembling that seen in colorectal hyperplastic polyps and composed of cells with cytologically bland basal nuclei and apical cytoplasmic mucin distention. The relationship of the HPC to the adenocarcinoma was noted in the Crohn's-related adenocarcinoma cases. An immunohistochemical stain for p53 (antibody DO7) was performed on all cases with HPC in both groups. HPC was identified in 10 of 30 (33%) cases of Crohn's-related adenocarcinoma compared with 3 of 30 (10%) cases in the control group (P = .03). In the 10 cases of Crohn's-related adenocarcinoma with HPC, this alteration was found adjacent to the adenocarcinoma in 3 cases, distant to the adenocarcinoma in 5 cases, and both adjacent to and distal from the adenocarcinoma in 2 cases. In two specimens, HPC was seen immediately adjacent to adenocarcinoma in the absence of adjacent dysplasia. p53 immunoreactivity was noted in HPC in 5 of 10 (50%) Crohn's-related adenocarcinomas. In contrast, p53 immunoreactivity was not seen in HPC in the three control cases with this mucosal alteration. In conclusion, HPC is found significantly more commonly in mucosa both adjacent to and distant from Crohn's-related adenocarcinoma when compared with age- and site-matched controls. In addition, p53 immunoreactivity is more commonly seen in HPC in cases of Crohn's-related adenocarcinoma compared with controls. These data suggest that this mucosal alteration may, in some cases, represent an unusual form of dysplasia in this setting.     

Can traditional “cupping” treatment cause a stroke?

The case study of a patient who developed haemorrhagic stroke after ‘cupping’ to the cervical area is presented. We consider the various manners in which cupping might induce haemorrhagic or ischemic stroke with particular reference to the relevant pathologies of the major cervical arteries. The other possible causes due to the induced cupping stresses are also examined using a computer based simulation study. Cupping of the cervical area may cause a haemorrhagic stroke by an acute rise in blood pressure. The tensile radial stresses generated by cupping may potentially facilitate the development of a dissection in the presence of an intimal tear. Moreover, the possible presence of micro-inclusions can intensify the local stress concentration for a thin cap.     

Two sibs with an unusual pattern of skeletal malformations resembling osteogenesis imperfecta: a new type of skeletal dysplasia?

We report a 6 year old boy with multiple fractures owing to bilateral, peculiar, wave-like defects of the tibial corticalis with alternative hyperostosis and thinning. Furthermore, he had Wormian bones of the skull, dentinogenesis imperfecta, and a distinct facial phenotype with hypertelorism and periorbital fullness. Collagen studies showed normal results. His sister, aged 2 years, showed the same facial phenotype and dental abnormalities as well as Wormian bones, but no radiographical abnormalities of the tubular bones so far. The mother also had dentine abnormalities but no skeletal abnormalities on x ray. This entity is probably the same as that described in a sporadic case by Suarez and Stickler in 1974. In spite of the considerable overlap with osteogenesis imperfecta (bone fragility, Wormian bones, and dentinogenesis imperfecta), we believe this disorder to be a different entity, in particular because of the unique cortical defects, missing osteopenia, and normal results of collagen studies.     

Halitosis: Could it be a predictor of stroke?

Stroke is a medical emergency and can cause permanent neurological disability and death. Halitosis (bad breath) has been reported in many stroke patients. We speculated that this phenomenon may be present before as well as after a stroke. Moreover, many studies have shown that most of the causes of halitosis are also associated with an increased risk of stroke. Therefore, we hypothesized that the severity of halitosis could be a predictor of stroke. We hope that this hypothesis can be confirmed by further investigations, and that if confirmed it can be used as a tool to monitor disease control and/or early diagnosis and intervention of newly developed diseases related to both halitosis and stroke.     

Too much too soon? Refeeding syndrome as an iatrogenic cause of delirium

BACKGROUND: Delirium is a significant and costly complication of medical hospitalization, and it has been shown to be a significant predictor of morbidity and mortality. It is often noted as a symptom in reported cases of refeeding syndrome, which is a potentially fatal complication in the treatment of patients suffering from malnutrition. OBJECTIVE: A case of delirium due to refeeding syndrome in a 61-year-old man is presented to help clinicians recognize this entity. The pathophysiology of refeeding syndrome and its possible role as an as-yet poorly-identified iatrogenic cause of delirium are discussed. METHOD: A diagnosis of delirium due to refeeding syndrome was made, and a nutrition consult was requested. Per nutrition recommendations, the patient was placed on a restricted calorie regimen, with aggressive supplementation of magnesium and phosphate. RESULTS: With his new dietary regimen, his mental status gradually improved, with complete resolution of his delirium by the 8th hospital day. He suffered no further episodes of confusion or disorientation. CONCLUSION: The relationship between refeeding syndrome and delirium may be of particular significance in the elderly, since malnutrition, medical hospitalization, and delirium are prevalent phenomena in this population.     

Developing a stroke intervention program: What do people at risk of stroke want?

OBJECTIVE: There is currently little research examining what individuals who are at risk of a stroke want from an invention program. In order to increase the usefulness of such programs, qualitative research methods were used explore invention design issues such as factors affecting accessibility of programs and preferred health information sources. METHODS: Thirty people, each with at least one stroke risk factor, participated in one of eight focus groups. RESULTS: Broad support was indicated for our proposed intervention. Participants perceived the value and likely success of such a program enhanced if it: (a) was integrated with, and supported by, other respected health services; (b) included social components (particularly important to women); (c) produced long-term benefits; and (d) included information that was personally relevant and practical in terms of implementing change. Three reasons emerged for continuing stroke education campaigns as a component of intervention programs; these were: (a) a lack of awareness among some participants of gaps in their stroke knowledge; (b) participants' explicit requests for specific rather than general information; and (c) the apparent failure of some participants to self-identify as at risk. CONCLUSION: This study yielded a number of important design considerations that should be taken into account when developing stroke intervention programs. PRACTICE IMPLICATIONS: We discuss ways of maximising the personal relevance of stroke prevention information along theoretically important dimensions, and consumers' recommendations for the design and delivery of stroke intervention programs.     

Atypical amyoplasia congenita in an infant with Leigh syndrome: A mitochondrial cause of severe contractures?

Amyoplasia congenita is a distinct form of arthrogryposis with characteristic features including internally rotated and adducted shoulders, extended elbows, flexion, and ulnar deviation of the wrists, and adducted thumbs. Fetal hypokinesia, secondary to a variety of genetic conditions, neuromuscular disorders, and environmental agents, is associated with contractures. In order to increase our understanding of the phenotypic spectrum associated with SURF 1 deficiency, a common cause of mitochondrial respiratory chain complex IV deficiency and Leigh syndrome, we describe a now 6-year-old boy who presented in the neonatal period with amyoplasia congenita. His development was normal until age 10.5 months, at which time he developed severe hypotonia and choreoathetosis following an episode of viral gastroenteritis. Following the onset of neurological symptoms, he gradually developed severe kyphosis and lower limb contractures. Blood and cerebrospinal fluid lactate levels were elevated and head imaging showed characteristic features of Leigh syndrome. He was found to harbor two pathogenic heterozygous mutations in the SURF 1 gene. In this case, mitochondrial dysfunction and the resultant energy deficiency may have played a role in causing abnormal neuronal development during embryogenesis, causing arthrogryposis. A variety of mitochondrial respiratory chain complex deficiencies have been associated with contractures of varying severity. Therefore, mitochondrial disorders should be considered in the differential diagnosis of neonatal arthrogryposis, especially if other characteristic findings such as lactic acidemia or basal ganglia abnormalities are present. ? 2012 Wiley Periodicals, Inc.     

Objective correlates of an unusual subjective experience: A single-case study of number–form synaesthesia

There is a universal and often unconscious tendency to mentally associate the number sequence with a spatial continuum (the mental number line). Here we study one individual who reports a strong and vivid sense of space when processing numbers. For him, the number sequence has a precise spatial form: a curvilinear right-to-left oriented line. We used various tasks to demonstrate that this numerical–spatial association is not a mere figment of his imagination, but a constrained experiential phenomenon consistent across sessions and automatically triggered by the visual presentation of numbers. We also show that this idiosyncratic representation can coexist with another implicit association, the SNARC effect (Spatial–Numerical Association of Response Codes, where small numbers are associated with the left side of space). This effect is present in individuals without explicit number forms and is not affected in the present subject in spite of his reversed subjective representation.     

Somatic mutation: a cause of sporadic neurodegenerative diseases?

The major causes of the common neurodegenerative diseases remain unknown. Alzheimer's disease, Parkinson's disease and motor neuron disease occur in both sporadic and familial forms, and mutations are progressively being found in families with these disorders. However, attempts to find causative mutations in blood DNA from the sporadic forms of the diseases have proved fruitless. It is hypothesised that this is because the causative mutations are found only in the cells in the central nervous system that are affected by the disease. These mutations arise in the developing embryo in progenitor cells of neurons or glia. The diseases are not passed to offspring since the mutations are not present in the germ-line. To find somatic mutations, the affected central nervous system cells need to be separated out and submitted to DNA analysis.     

Premature ageing of the immune system: the cause of AIDS?

The reasons for the failure of the immune system to control HIV-1 infection, and the resulting immunodeficiency, remain unclear. HIV-1 persists in its host despite vigorous immune responses, including a strong, and probably functional, HIV-specific cytotoxic T-lymphocyte response. Interestingly the immunological features of HIV-1-infected individuals show many similarities to those seen in elderly people without HIV infection. We propose that, through a process of continuous immune activation, HIV-1 infection leads to an acceleration of the adaptive immune system ageing process, resulting in premature exhaustion of immune resources, which participates in the onset of immunodeficiency. This hypothesis might shed new light on HIV-1 pathogenesis and could suggest the need to reconsider current immunotherapeutic strategies to fight the virus.     

Fetomaternal cell trafficking: a new cause of disease?

Isolation of fetal cells from maternal blood is under active investigation as a noninvasive method of prenatal diagnosis. In the context of studying cell surface antigens expressed on fetal cells we discovered that fetal cells from a prior pregnancy also could be detected. This led to the appreciation of the persistence of fetal cells in maternal blood for as long as 27 years postpartum, and the realization that following pregnancy, a woman becomes a chimera. Quantitative polymerase chain reaction analyses have shown that a term pregnancy is not required for the subsequent development of fetal cell microchimerism. As many as 500,000 fetal nucleated cells are transfused following an elective first trimester termination of pregnancy. The relationship between fetal cell microchimerism and maternal disease is currently being explored. During pregnancy, fetal cells in the maternal skin are related to polymorphic eruptions of pregnancy and increased fetomaternal trafficking is detectable in cases of preeclampsia. After delivery, more male DNA of presumed fetal origin is present in the blood and skin of women with scleroderma as compared with healthy controls. Scleroderma is of particular interest because it shows a strong female predilection and it is an autoimmune disease with clinical similarities to graft-versus-host disease. Fetomaternal cell trafficking provides a potential explanation for the increased prevalence of autoimmune disorders in adult women following their childbearing years.     

Fetomaternal cell trafficking: A new cause of disease?

Isolation of fetal cells from maternal blood is under active investigation as a noninvasive method of prenatal diagnosis. In the context of studying cell surface antigens expressed on fetal cells we discovered that fetal cells from a prior pregnancy also could be detected. This led to the appreciation of the persistence of fetal cells in maternal blood for as long as 27 years postpartum, and the realization that following pregnancy, a woman becomes a chimera. Quantitative polymerase chain reaction analyses have shown that a term pregnancy is not required for the subsequent development of fetal cell microchimerism. As many as 500,000 fetal nucleated cells are transfused following an elective first trimester termination of pregnancy. The relationship between fetal cell microchimerism and maternal disease is currently being explored. During pregnancy, fetal cells in the maternal skin are related to polymorphic eruptions of pregnancy and increased fetomaternal trafficking is detectable in cases of preeclampsia. After delivery, more male DNA of presumed fetal origin is present in the blood and skin of women with scleroderma as compared with healthy controls. Scleroderma is of particular interest because it shows a strong female predilection and it is an autoimmune disease with clinical similarities to graft‐versus‐host disease. Fetomaternal cell trafficking provides a potential explanation for the increased prevalence of autoimmune disorders in adult women following their childbearing years. Am. J. Med. Genet. 91:22–28, 2000. © 2000 Wiley‐Liss, Inc.     

A clinical and neuropathological study of an unusual case of sporadic tauopathy. A variant of corticobasal degeneration?

We report a sporadic case of tauopathy with unusual clinical and neuropathological features. The patient presented with progressive symmetric rigid-akinetic parkinsonism and dementia of the subcortical type. Magnetic resonance imaging of the brain revealed atrophy resembling multiple system atrophy. The level of cerebrospinal fluid tau protein phosphorylated at serine 199 was markedly elevated. The autopsy revealed more glial than neuronal tauopathy, with much heavier involvement of subcortical white matter and the brainstem than of the cerebral cortex. Analysis of dephosphorylated tau revealed that hyperphosphorylated four-repeat tau isoforms were deposited in the brain of the patient. Despite morphological and biochemical resemblance to a certain form of familial fronto-temporal dementia, no mutation of the tau gene including exon 10 could be found. Our findings, taken together with those in previous similar case reports, indicate that the case represents an atypical form of corticobasal degeneration or a new variant of sporadic tauopathy.     

Dysfunction of the anterior hippocampus: The cause of fundamental schizophrenic symptoms?

Recent evidence suggests there is an association between schizophrenia and dysfunction of the anterior hippocampus. Accordingly, this paper endeavors to show how the fundamental schizophrenic symptoms described by Bleuler might arise from deficiencies in normal hippocampal function. This effort is based on the idea that the hippocampus normally constructs a composite picture or worldview of the environment when conditions are novel or uncertain. Then when conditions become familiar, it influences emotion and behavior to be consistent with that worldview. The anterior hippocampus maintains the emotional component of a worldview through its interaction with the amygdala and hypothalamus, and supports executive frontal lobe activity by way of its output to the nucleus accumbens. From this perspective, the split between affect and cognition in schizophrenia is attributed to a failure of the anterior hippocampus to enforce the emotional component of a worldview allowing emotions to diverge from the cognitive component. The splitting of associations is traced to a failure of anterior hippocampal output to support frontal lobe control over the flow of associations. And a split from reality is seen to arise from a combination of these two failures. The individual ceases to interact with the world because the lack of executive control makes such interaction difficult. Fear and fantasies come to dominate experience because emotions are not adequately controlled.     

The oxidative stress hypothesis of atherosclerosis: cause or product?

The oxidative stress hypothesis postulates that endogenous free radicals of unknown origin, possibly derived from mural cells, oxidize low density lipoproteins and that oxidation products are allegedly responsible for initiation and progression of atherosclerosis. The thesis fails to explain its topography, site specific severity and the iatrogenic and experimental hemodynamic induction of atherosclerosis under conditions complying with the logic of Koch's postulates. Free radicals are generated by biomechanical scission of macromolecules and polymers, the biophysical mechanism underlying bioengineering fatigue in atherogenesis with oxidative damage a secondary, contributory factor to mural pathology. The plentiful supply of antioxidants negates oxidative stress as the dominant factor in atherogenesis.