Jerome Albert Ecker, MD

https://medicine.duke.edu/faculty/jerome-albert-ecker-md

Oligodendrogliomas may also spread into the leptomeninges and asthmatic bronchitis treatment guifasen purchase 100 mcg albuterol amex, occasionally, grow primarily as leptomeningeal masses. Minute calcifications are most common alongside or within the delicate vasculature. These include nuclear atypia and pleomorphism, high cellularity, brisk mitotic activity, endothelial hypertrophy and microvascular proliferation, as well as necrosis. Collectively, these morphological features are similar to those commonly used for the grading of diffuse astrocytic gliomas. However, their individual impact on grading and their integration into an objective and reproducible grading 1676 Chapter 28 Oligodendroglial Tumours system of oligodendrogliomas is less established. A study by seven independent neuropathologists identified older patient age, high cellularity, presence of mitoses, endothelial hypertrophy and proliferation, and necrosis significantly associated with shorter survival on univariate analysis in a cohort of 124 patients. As a rule, the histological diagnosis of an anaplastic oligodendroglioma should require either the presence of conspicuous endothelial proliferation and/or high mitotic activity. Thus, modern assessment of oligodendroglioma behaviour should consider clinical and neuroimaging findings, histological grading, proliferation indices and molecular genetic characteristics. Immunohistochemistry Immunohistochemical studies may provide useful information for the classification and grading of oligodendroglial tumours. However, a specific and sensitive immunohistochemical marker of oligodendroglial tumours is still lacking. Nevertheless, certain immunohistochemical staining patterns may be helpful to distinguish oligodendrogliomas from most other brain tumour entities. Such staining of tumourinfiltrated neuropil should not be mistaken as neuronal or neurocytic tumour differentiation. However, some oligodendrogliomas, including cases with combined losses of 1p and 19q, contain tumour cells with morphological features indicative of neuronal/neurocytic differentiation and immunohistochemical positivity for synaptophysin and other neuronal markers. In general, the mean fraction of positive tumour cells is Oligodendroglioma 1677 significantly higher in anaplastic oligodendrogliomas as compared to low-grade oligodendrogliomas. Cytological preparations from tissue smears most readily permit the identification of macrophages with their vacuolated cytoplasm and accompanying reactive astrocytes. These cells often lie clustered around blood vessels in association with lymphocytes, but perivascular macrophages may also be present in otherwise typical oligodendrogliomas. Partial lobectomy specimens performed for intractable seizures not infrequently have seemingly increased numbers of oligodendrocytes. In such instances, however, the white matter is condensed with resultant crowding of oligodendroglial nuclei, whereas the accompanying astrogliosis further contributes to the increased cellularity.

Most patients with spinal epidural abscess have at least one predisposing condition occupational asthma definition cheap albuterol 100 mcg without prescription. Contiguous spread accounts for approximately one-third of cases; approximately 50 per cent of cases occur via haematogenous bacterial dissemination,23 originating from the skin and soft tissues. The dura mater approaches the periosteum to create a true epidural space posterior and lateral to the spinal cord, in the thoracic and lumbosacral levels,138 which are most often involved, although the cervical levels are less frequently involved. The abscess may extend over several (mostly 3 to 4) vertebral levels;23,169 extension along the entire length of the spinal cord has been reported. Abscesses located anteriorly to the spinal cord are frequently, but not exclusively, associated with vertebral osteomyelitis. The composition of the inflammatory infiltrate is similar to that in pyogenic bacterial meningitis and depends on the age of the lesion. Most cases evaluated by neuropathology, are from a chronic stage, frequently after repeated orthopaedic injections. Biopsies show chronic inflammation with infiltrates consisting predominantly of lymphocytes and plasma cells within granulation tissue. Complete investigation of the biopsy material is Mycobacterial Infections 1209 required to exclude small foci of acute inflammation with pus and polymorphonuclear leukocytes. From primary infection of the nucleus pulposus, the infection spreads to adjacent bony endplates. All levels of the spine may be affected, and infection may spread to epidural and paravertebral sites. In the differential diagnosis, an underlying tumour should be considered that may have induced a strongly inflammatory fibrosing reaction. The aetiology of hypertrophic pachymeningitis is unknown, but autoimmune diseases. Recurrence after surgical decompression and immunosuppressive therapy has been reported in 12 per cent of patients with spinal hypertrophic pachymeningitis within a period ranging from 3 months to 2 years (mean 1. Central Nervous System tuberculosis Aetiology and Epidemiology Although the incidence of tuberculosis has declined over the last century, it still poses a serious medical problem in developing countries. However, it is clinically important and constitutes a serious, potentially devastating complication with high morbidity and high mortality. Approximately 4 per cent of children with tuberculosis will develop tuberculous meningitis. Neuropathology In the acute phase, inflammation is characterized by neutrophils, macrophages and bacteria; cartilage and bony endplates may be necrotic, and pus may be detected. With time, the inflammatory infiltrate changes to predominantly lymphocytes and plasma cells, and vascularized granulation tissue develops. Both the cranial and spinal dura may be involved; cranial disease mainly affects the base of the skull and the posterior fossa, whereas most spinal disease involves the cervical and thoracic levels, and may be solitary or multiple, diffuse or nodular. Concentric layers of dense fibrous tissue underlie dural hypertrophy, mixed with inflammatory cells consisting of lymphocytes, polyclonal plasma cells and, occasionally, Pathogenesis M.

Multiple infections by different strains can occur in a single host asthma symptoms vs copd cheap albuterol 100 mcg overnight delivery,760,1069 particularly if immunocompromised. Over half of the population is seropositive by 25 years and over 80 per cent by 35 years. The risk of primary maternal infection during pregnancy and of consequent fetal infection is therefore greater in higher socioeconomic groups, within which up to 50 per cent of pregnant women may still be susceptible. The subependymal tissue may be extensively necrotic and usually contains large numbers of cytomegalic inclusion cells. The most severe form of congenital infection is disseminated cytomegalic inclusion disease,826 which manifests shortly after birth with petechiae (in 80 per cent of cases), hepatosplenomegaly (75 per cent), jaundice (65 per cent), microcephaly (50 per cent) and chorioretinitis (12 per cent) and often runs a fatal course within days or weeks. Surviving infants may have microcephaly, severe metal retardation, seizures, spasticity, severe hearing loss, chorioretinitis and optic atrophy. Infants with less severe perinatal disease may present in later infancy with ophthalmic and auditory impairment, and microcephaly. In milder cases, deafness, or minimal brain dysfunction with intellectual and behavioural problems, may become apparent only later in life. The brain is usually small and may show porencephaly or polymicrogyria; less frequent findings include hydrocephalus, lissencephaly and cerebellar hypoplasia. The larger foci of calcification are macroscopically visible as granules of hard white material. The degree of residual inflammation on microscopic examination depends on the timing of examination in relation to the acute neonatal disease. Most cases show obvious meningoencephalitis, and cytomegalic inclusions can be found in all cellular elements of the brain, including 1124 Chapter 19 Viral Infections 19. There is mild ventricular dilation, and discolouration and sloughing of the ependymal surface. The partially ulcerated ependymal surface and oedematous subependymal tissue contain numerous immunolabelled cytomegalic cells (red). Cytomegalic cells are most numerous in periventricular regions, particularly around the lateral ventricles. Foci of mineralization are present in the grey and white matter, most with little associated inflammation. Central nervous system disease complicating postnatal infection is characterized histologically by the presence of numerous microglial nodules scattered throughout the brain. These are not usually associated with mineralization and contain only occasional cytomegalic cells with inclusions. Reports describe multifocal lymphohistiocytic inflammation of grey and white matter and, in some cases, haemorrhage or necrosis. The ventricles are moderately dilated, and several foci of calcification are visible in the periventricular region (arrows). The virus is transmitted both non-sexually, probably through saliva, and sexually, particularly among homosexual men.

Of all intracranial tumours asthma allergy immunology trusted albuterol 100 mcg, roughly 40 per cent originate from neuroepithelium, 35 per cent from meningothelial cells, 14. In addition, the mortality/incidence ratio for brain tumours reflects the effectiveness of diagnostic and therapeutic measures. Mortality is lower overall in women, given their lower incidence of gliomas and increased predisposition to meningiomas. Not surprisingly, mortality and morbidity are also highly associated with site of presentation, both increasing considerably when eloquent brain is involved. The age distribution of brain tumours is bimodal, with the first peak in children. In general, gliomas and embryonal tumours occur more frequently in males, whereas meningiomas preferentially affect females. Meningiomas account for 43 per cent of primary intracranial tumours in women as compared to only 22 per cent in men. There has been some concern over a possible increase in the incidence of brain tumours since the 1980s, but most authors agree that this apparent increase is largely due to the introduction and more frequent utilization of high-resolution neuroimaging, which has greatly improved the sensitivity of detecting brain tumours. For instance, one international series evaluating 75 glioma families found evidence of Mendelian inheritance and a susceptibility locus at 17q12-21. Of interest, several of these risk loci involve genes already known or suspected to be critical in glioma biology, including 5p15. Numerous epidemiological studies have been performed, but most associations with environmental, dietary and lifestyle factors either have not been statistically significant or are inconsistent. In most reported cases, radiation was administered for treatment of the fungal disease tinea capitis or of a cranial tumour unrelated to the radiation-induced neoplasm, although epidemiological studies following atomic bomb detonations in Japan have similarly provided compelling evidence. Sarcomas (mostly fibrosarcomas and malignant peripheral nerve sheath tumours) of the dura, meninges, or nerves are less frequent but, given their extreme rarity sporadically, are highly indicative of iatrogenic origin if diagnosed in patients with prior therapeutic irradiation. Although a causative role of radiotherapy is generally acknowledged, the possible risk of diagnostic X-rays. Long-term low-dose radiation exposure of nuclear workers has not been definitively implicated to increase risk of brain tumours. Cellular phones utilize radio-frequency waves that fall between radiowaves and microwaves. Radio-frequency wave exposure is related to the duration and frequency of cellular phone use, with increased use implying increased exposure. In general, the studies using experimental systems to evaluate the effects of such radio-frequency exposures have not shown biological effects that are directly relevant to the situation encountered in human brain tumours. Thus, although biological effects may be found after exposure, these may have little to do with human brain tumourigenesis. More importantly, well-conducted epidemiological studies have failed to document clear associations with increased risk of gliomas, meningiomas or vestibular schwannomas, possibly with the exception of those at the highest exposure levels, although biases in study designs have prevented definitive interpretations. Of note, one group from Sweden has reported an increased risk for brain tumours ipsilateral to the side of cell phone use, not for malignant tumours, but only when vestibular schwannomas are included in the analysis.

Some of the more relevant models of gliomas asthma diagnosis albuterol 100 mcg order mastercard, medulloblastomas, nerve sheath tumours and meningiomas are covered elsewhere and the reader is referred to a number of reviews for additional information. Further incorporation of progression associated alterations, such as Pten loss, generally results in highgrade gliomas exclusively. One approach generated mice with heterozygous inactivation of Nf1 and Trp53 in a cis configuration (residing on the same chromosome). These animals developed a range of histologically typical low-grade astrocytomas to glioblastomas with a penetrance of 100 per cent at 6 months. For these reasons, such mice may prove to be a highly useful model of astrocytoma formation and progression. Only those cells expressing the retroviral receptor can be infected by the virus and express the oncogene. Remarkably, these cells will then generate tumours of divergent (astrocytic, oligodendroglial and neuronal) differentiation when introduced into nude mouse brains. Crossing these mice into an Ink4adeficient or Tp53-deficient background then produces high-grade oligodendrogliomas. Therefore, it is not surprising that many attempts have been made to produce classifications that accurately reflect prognosis and response to particular therapies. The aim to produce such a classification has been frustrated not only by lack of knowledge concerning histogenesis and tumourigenesis at a biological level, but also by the variably subjective nature of histological parameters. The classification of neoplasms can be based on morphological features, biological behaviour, cells of origin, histological resemblances, expression of particular molecules and genetic abnormalities. The introduction of modern investigative methods into neuro-oncology has been instrumental in devising classifications that take more than one aspect of each tumour into consideration. Electron microscopy, tissue culture, immunohistochemistry, biology and molecular genetics have all substantially contributed to the understanding of the neoplastic process and, in doing so, have greatly improved the definitional criteria on which tumour classifications are based. It must be emphasized that tumour classification is a dynamic process that is nestled between pathological approaches to diagnosis, radiological techniques, biological advances and improvements in therapy. Classification can, and must, change in response to improved understanding and abilities in each of these areas. For example, the advent of a new effective therapy raises the possibility that particular histological or molecular features correlate with response to the new therapy. On the other hand, molecular advances now commonly outpace clinical neuro-oncology. For instance, recent high throughput genomics data suggest that there are at least four molecular subtypes each of glioblastoma and medulloblastoma. Furthermore, although classification systems must be dynamic, they must refrain from excessive flux, in order to retain stability in the treatment of individual patients. In this regard, changes in classification must be based on highquality validated data. Many classification systems have been put forth for brain tumours over the past 100 years.

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