Old carbon reservoirs were not important in the deglacial methane budget.

Permafrost and methane hydrates are large, climate-sensitive old carbon reservoirs that have the potential to emit large quantities of methane, a potent greenhouse gas, as the Earth continues to warm. We present ice core isotopic measurements of methane (Δ14C, δ13C, and δD) from the last deglaciation, which is a partial analog for modern warming. Our results show that methane emissions from old carbon reservoirs in response to deglacial warming were small (<19 teragrams of methane per year, 95% confidence interval) and argue against similar methane emissions in response to future warming. Our results also indicate that methane emissions from biomass burning in the pre-Industrial Holocene were 22 to 56 teragrams of methane per year (95% confidence interval), which is comparable to today.

Enhanced climate instability in the North Atlantic and southern Europe during the Last Interglacial.

Considerable ambiguity remains over the extent and nature of millennial/centennial-scale climate instability during the Last Interglacial (LIG). Here we analyse marine and terrestrial proxies from a deep-sea sediment sequence on the Portuguese Margin and combine results with an intensively dated Italian speleothem record and climate-model experiments. The strongest expression of climate variability occurred during the transitions into and out of the LIG. Our records also document a series of multi-centennial intra-interglacial arid events in southern Europe, coherent with cold water-mass expansions in the North Atlantic. The spatial and temporal fingerprints of these changes indicate a reorganization of ocean surface circulation, consistent with low-intensity disruptions of the Atlantic meridional overturning circulation (AMOC). The amplitude of this LIG variability is greater than that observed in Holocene records. Episodic Greenland ice melt and runoff as a result of excess warmth may have contributed to AMOC weakening and increased climate instability throughout the LIG.

Dissecting hematoma of intracranial internal carotid artery in an 8-year-old girl.

BACKGROUND: An 8-year-old girl had a minor fall without head trauma and she collapsed the following day while playing. She was awake but mute with focal neurologic signs when admitted to hospital. Radiologic imaging studies showed a progressive left cerebral infarct with left hemisphere vascular narrowing and beading. She died on the third hospital day. METHODS: Autopsy including exploration of neck vessels and neuropathological examination was performed. Postmortem studies included immunostaining for immunoglobulins and fixed complement. RESULTS: Subtotal subintimal dissections of both proximal supraclinoid internal carotid arteries were found microscopically. On the left, the subintimal dissection extended into the major branches of the left internal carotid artery as dissecting hematomas with a major compromise of the arterial lumina. Specific IgM deposition at the dissection sites was found. A literature review shows that subintimal dissection of the intracranial internal carotid artery or its branches occurs rarely, it is often fatal, and it is present in patients with a mean age of 17.5 years in cases studied pathologically. Trauma and physical exertion are the most common associated factors. CONCLUSIONS: Among the causes of ischemic stroke in young individuals, dissecting hematomas of the intracranial portions of the internal carotid artery system rank low. Few reported cases have identifiable pre-existing pathology. The pathogenesis of dissecting hematomas in this region is reviewed and expanded with speculation regarding relevant developmental, anatomical, flow stress and possibly humoral factors that are involved in the disruption of the arterial elastica and subsequent development and extension of a subintimal hematoma resulting in luminal closure and often death.

Nucleus of the tractus solitarius metastasis: relationship to respiratory arrest?

BACKGROUND: A 52-year-old woman with metastases in brain and bone had clinical and radiological response to therapy but died about 10 weeks after diagnosis. General autopsy failed to identify a primary neoplasm or an anatomic cause of death. Investigation of sudden respiratory cessation was a consideration when undertaking an anatomic study of the brain. METHODS: Review of patient records and careful examination of the brain following autopsy were carried out. RESULTS: The patient had terminal episodes of hypersomnia but episodes of sleep apnea were not observed. She received no respiratory support and no respiratory difficulties were recorded until she was pronounced dead at 7 a.m. Autopsy revealed metastatic adenocarcinoma in a pattern suggestive of a primary pulmonary neoplasm, including multiple cerebral metastases, although no significant pulmonary lesions of any type were found. A 0.2 cm metastatic adenocarcinoma was found in the nucleus of the tractus solitarius (NTS). No other tumor was present in the brain stem. CONCLUSIONS: Unilateral destruction of the NTS in the medulla would have severely disturbed the most critical point of convergence of autonomic and voluntary respiratory control and of cardiocirculatory reflexes in the central autonomic network. It is postulated that this caused respiratory arrest during a state transition from sleeping to waking. Few metastases to the medulla are reported, most are relatively large, and several have caused respiratory symptoms before death. The very small metastasis in our patient could be the direct anatomic cause of death, and as such it is an unusual complication of metastatic disease of which clinicians should be aware. It is speculated that dysfunction of direct NTS connections to the pons or of connections passing close to the metastatic deposit resulted in terminal hypersomnia.

Biological evaluation of biopsies from adult cerebral astrocytomas: cell-growth/cell-suicide ratios and their relationship to patient survival.

In adult cerebral astrocytomas, the more anaplasia that is present, the more malignancy that occurs. Cell proliferation antigen staining (MIB-1) and DNA labeling methods for apoptosis using paraffin sections from 39 cases were compared with histopathological grading systems for predicting patient survival. Cases were selected to include those with expected or unexpected survival time for grade. Computer-assisted image analysis data were used to construct proliferation-apoptosis indices to compare with tumor grade and patient survival. Cases with less proliferation than apoptosis usually had a favorable outcome regardless of tumor grade, with some unexpectedly long survivals among high-grade cases. Cases with more proliferation than apoptosis had a poor outcome, including most patients with high-grade astrocytomas and a few patients whose tumors were low grade but whose indices were high. The in situ tailing method for apoptosis revealed many nuclei with low levels of DNA strand breaks, particularly in older, nonsurviving patients. Tumor growth indices may be useful for prognosis and they may also become adjunctive guides for therapy by indicating rates of tumor growth and spontaneous apoptosis that therapy can affect. Perhaps the apoptotic mechanism cannot be completed spontaneously or boosted as easily by conventional therapy as patients age.

Multifocal varicella-zoster virus leukoencephalitis in a patient with AIDS: MR findings.

We describe a patient with AIDS who presented with an acute encephalitis caused by infection with varicella-zoster virus. The hemorrhagic, necrotizing encephalitis had an unusual MR appearance, with innumerable discrete, small, targetlike lesions in the right cerebral hemisphere, which were coalescent in the posterior temporal, parietal, and occipital regions. Of the several known disease patterns of varicella-zoster viral infection in the CNS, this histopathologic pattern of multifocal leukoencephalitis is rare. It is important to recognize, as effective antiviral drug treatments are available.

Regulation of HIV-1 infection in astrocytes: expression of Nef, TNF-alpha and IL-6 is enhanced in coculture of astrocytes with macrophages.

'Restricted' human immunodeficiency virus type (HIV-1) infection of astrocytes is recognized in vivo in some pediatric and adult AIDS brains and in vitro in a small proportion of transfected primary fetal astrocytes. We investigated the extent of HIV-1JR-FL expression in fetal astrocytes and macrophages cultivated alone or together. Peak HIV-1 p24 antigen titres in supernatant fluids of macrophage cultures were increased with monocyte/macrophages from certain donors and were higher when macrophages were cocultivated with astrocytes. Structural HIV-1 gene (gp 41 and pol) products (protein and mRNA) were observed only in macrophages. Ten days after HIV-1JR-FL infection, astrocytes in a monoculture were stained negative or only weakly positive (1-2+) for Nef, whereas in a coculture up to 100% of astrocytes displayed Nef staining (up to 4+) in the cytoplasm. The streptavidine-biotine-peroxidase technique with certain monoclonal antibodies to Nef (Ovod et al, 1992) was specific for infected astrocytes. The intensity of Nef staining was higher in astrocytes cultivated with monocyte/macrophages from certain donors. In the coculture, tumor necrosis factor-alpha (TNF-alpha) was expressed in the astrocyte cytoplasm earlier after coinfection with HIV-1 and cytomegalovirus (CMV) compared to infection with HIV-1 alone. Interleukin-6 (IL-6) was secreted spontaneously and transiently in uninfected cocultures, but in a prolonged fashion following HIV-1 and HIV-1/CMV infections. The interactions between HIV-1- and CMV-infected macrophages and astrocytes lead to upregulation of TNF-alpha and IL-6 and enhancement of productive HIV-1 infection of macrophages and of 'restricted' HIV-1 infection of astrocytes with implications for the pathogenesis of AIDS dementia.

Ophthalmologic manifestations of acquired immune deficiency syndrome-associated progressive multifocal leukoencephalopathy.

PURPOSE: Progressive multifocal leukoencephalopathy (PML) is increasingly described as a late complication of the acquired immune deficiency syndrome (AIDS). The purpose of this study is to evaluate retrospectively the ophthalmologic, clinical, and investigational aspects of AIDS-associated PML. METHODS: The authors evaluated ten patients in whom ophthalmologic manifestations developed in the course of AIDS-associated PML. Findings at clinical examination and their progression over time, neuroimaging correlates, the results of pathologic investigation, and visual outcomes were reviewed. RESULTS: Progressive multifocal leukoencephalopathy was the AIDS-defining illness in six of ten patients. Homonymous visual field defects were the presenting symptom in three patients and detected in six patients overall. Occipital blindness developed in one patient. Cerebellar signs and brain stem nuclear and supranuclear palsies also were common. Confluent white matter lesions with increased intensity on T2-weighted magnetic resonance imaging were supratentorial in seven patients and infratentorial in three patients. With incomplete data, the median survival time was 3 months from PML onset. Histopathologic confirmation of PML diagnosis was available for nine of the ten patients. CONCLUSIONS: The development of progressive retrochiasmal visual field defects, supranuclear and nuclear cranial nerve palsies, or nystagmus ataxia in the relatively young patient should alert the ophthalmologist to the possibility of PML, particularly in the presence of long-tract central nervous system signs or dementia. Progressive multifocal leukoencephalopathy will often be human immunodeficiency virus associated. Human immunodeficiency virus encephalopathy, cerebral toxoplasmosis, lymphoma, and infarction need to be discriminated. Effective therapy is required urgently for this devastating disease.

Leptomeningeal and calvarial sarcoidosis: CT and MR appearance.

We report an unusual case of biopsy-proven combined leptomeningeal and calvarial sarcoidosis, as seen on CT and MRI. A solitary large thick plaque was present in the left hemisphere, with overlying bony infiltration and erosion and associated abundant vasogenic edema in the brain. The lytic lesion was visible on Scout digital radiography for CT slice positioning. The typical manifestations of CNS sarcoidosis, i.e., chronic leptomeningitis in the basilar cisterns and hypothalamic regions, were absent.

Primary angiitis and angiopathy of the central nervous system and their relationship to systemic giant cell arteritis.

Three cases of primary angiitis of the central nervous system were compared with previously published cases. Most cases occurred in older adults, were diagnosed histologically, and had a male-female ratio of 2:1. Angiographically identified cases, demonstrating angiopathy but not necessarily vasculitis as might be seen in histologically identified cases, were found in younger adults and showed a male-female ratio of 1:2. The autopsy cases had some similarities to systemic giant cell arteritis, including many cases with vasculitis in large branches of the circle of Willis and foci of systemic vasculitis. Vasculitides in arteries of different sizes may result from different responses to a variety of antigens or immune complexes rather than represent different disease processes. If causative immune mechanisms can be identified, primary angiitis of the central nervous system may become classified immunologically rather than histopathologically.

Intraventricular cerebral neuroblastoma. Analysis of subtypes and comparison with hemispheric neuroblastoma.

Two cases of intraventricular neuroblastomas were compared with cases of intraventricular and hemispheric neuroblastomas that have been reported in the published literature. The following order of tumor subtypes was found in patients with increasing age: hemispheric neuroblastoma, intraventricular undifferentiated neuroblastoma, intraventricular differentiated neuroblastoma, and intraventricular neurocytoma; for patients with intraventricular neuroblastomas, this was also the order of increasing cellular maturation and survival. Neuronal morphologic or epitope differentiation was associated with a longer survival time than lack of differentiation by Kaplan-Meier product-limit estimates and with a better survival rate (chi 2) for intraventricular tumors but not for hemispheric tumors. Pathologic distinction of a neurocytoma was confirmed with immunostaining or ultrastructural studies that suggested that a neurocytoma is a matured neuroblastoma of a granule-cell (interneuron) phenotype. Differences among neuroblastoma groups bolster previous suggestions that intraventricular tumors arise differently than do cases of hemispheric tumors and follow a more benign course when neuronal differentiation is present.

Expression of HIV-1 and interleukin-6 in lumbosacral dorsal root ganglia of patients with AIDS.

We examined the immunopathology and the expression of human immunodeficiency virus type 1 (HIV-1) in lumbosacral dorsal root ganglia (DRGs) from 16 patients with acquired immunodeficiency syndrome (AIDS) and 10 HIV-1-seronegative controls. Using in situ hybridization, we detected HIV-1 RNA in a few perivascular cells in DRGs from five of 16 AIDS patients (31%). In addition, using polymerase chain reaction, we detected HIV-1 DNA more frequently in DRGs from four of five AIDS patients (80%) examined. We detected interleukin-6 (IL-6) immunoreactivity in endothelial cells in DRGs from seven of 16 AIDS patients (44%) but from none of 10 HIV-1-seronegative controls (0%). We found more nodules of Nageotte, CD8+ T lymphocytes, and intercellular adhesion molecule-1 (ICAM-1)-positive endothelial cells and mononuclear cells in DRGs from AIDS patients than in DRGs from controls. Increased numbers of nodules of Nageotte in DRGs of AIDS patients were associated with detection of HIV-1 RNA by in situ hybridization and detection of IL-6 by immunohistochemistry. We conclude that low levels of replication of HIV-1, through cytotoxic T lymphocytes or expression of cytokines, may play a role in the subclinical degeneration of sensory neurons frequently observed in DRGs of AIDS patients.

Histopathologic features in the central nervous system of 400 acquired immunodeficiency syndrome cases: implications of rates of occurrence.

Histopathologic lesions in the central nervous system (CNS) of 400 autopsy cases of the acquired immunodeficiency syndrome (AIDS) collected from 1982 to 1990 were studied. Lesions most closely associated with human immunodeficiency virus (HIV) infection in the CNS (perivascular macrophages, nodular encephalomyelitis, diffuse leukoencephalopathy, necrotizing encephalitis, and long-tract degeneration) were found in 20% of the cases. The group of vascular and inflammatory lesions and of opportunistic infections was seen in 25% of cases. These two lesion groups were found together in 32% of cases, and none of these lesions was present in 23% of cases (most of the latter having no significant CNS lesions). Length of survival increased in the last group of 100 cases compared with the first 300 cases. The homosexual and bisexual risk groups showed continuously increasing lengths of survival for each category of HIV-associated CNS lesions throughout the study, while the lengths of survival in the other risk groups varied. Patients in the last group of 100 autopsy cases with any HIV-associated lesion survived longer than patients without these lesions. The AIDS patients with no CNS lesions had the shortest mean length of survival. The results suggest that although survival is prolonged as specific therapy is given, there is an increase in CNS lesions in AIDS patients with longer survival. This may indicate that CNS lesions in AIDS are generally dependent on systemic disease progression over many months as immune function decreases.

AIDS dementia complex complicated by cytomegalovirus encephalopathy.

We have studied longitudinally ten patients with AIDS encephalopathy with respect to pathogenetic roles of human immunodeficiency virus (HIV) and cytomegalovirus (CMV). Three patients manifested typical AIDS dementia complex (ADC) (initially without retinitis and with slowly progressive cognitive, motor and behavioral abnormalities which were zidovudine-responsive, and relatively preserved CD4+ T cells), and seven patients presented with AIDS dementia complex complicated by CMV encephalopathy (ACE) (with CMV retinitis, peripheral neuropathy, altered sensorium, and rapidly declining clinical and immunological status). Whereas only HIV antibody was elevated in the spinal fluid of patients with ADC, both virus infections were active in the central nervous system of patients with ACE as shown by HIV p24 antigenemia and antigenrrhachia, elevated HIV and CMV antibody in the spinal fluid, disseminated CMV infection with retinitis, and basilar ventriculoencephalitis with multinucleated cytomegalic cells containing CMV and HIV proteins and CMV DNA. The recognition of ADC and ACE is important, since some patients with ACE may respond to ganciclovir or foscarnet.

HIV-1 in postmortem brain tissue from patients with AIDS: a comparison of different detection techniques.

OBJECTIVE: The presence of HIV-1 in postmortem brain tissue from 31 patients with AIDS and 12 HIV-1-negative controls was investigated. DESIGN: Most laboratories have access to the methods used. We readily applied in situ hybridization and immunohistochemistry to archival formalin-fixed paraffin-embedded (FFPE) brain specimens. METHODS: The techniques used to detect HIV-1 were explant culture, in situ hybridization with 35S-labeled polymerase (pol) gene riboprobes and immunohistochemistry with monoclonal antibody to gp41. RESULTS: HIV-1 was isolated from explant cultures in 13 out of 20 (65%) patients, whereas HIV-1-infected cells were detected in FFPE brain tissue from nine out of 26 (35%) patients examined by in situ hybridization and in seven out of 26 (27%) patients examined by immunohistochemistry. CONCLUSIONS: Although the isolation technique was the most sensitive of the three techniques tested, infected cells may be identified with in situ hybridization in conjunction with immunohistochemistry.

Evidence of serum-protein leakage across the blood-brain barrier in the acquired immunodeficiency syndrome.

Lesions of the central nervous system (CNS) in 23 patients with the acquired immunodeficiency syndrome (AIDS) were compared with control cases for the presence of serum protein by immunoperoxidase staining. A sensitive immunostaining kit in conjunction with rabbit antisera to human serum, albumin, immunoglobulins and complement component 3c was used to demonstrate specific immunoreactivity in paraffin-embedded sections. Most AIDS patients with CNS lesions had serum protein immunoreactivity in some neurons, glial cells (including astrocytes), gliomesenchymal cell nodules, vascular endothelial cells, inflammatory cells or microvascular walls. Cases with the most necrosis tended to have the least immunostaining. Immunoreactivity for IgG and fixed complement in anatomically intact or morphologically altered neural cells may indicate cellular lesions and potential cellular necrosis beyond the damage indicated by routine studies alone. Part of this immunoreactivity might represent a humoral autoimmune response.

Hyperbaric oxygen treatment for carbon monoxide poisoning: observations based on 8 years experience.

Patients may develop significant carbon monoxide intoxication under a variety of circumstances. We propose that the frequency of symptoms, the patient's presentation, and ultimately the outcome are significantly related to the type of exposure. This association may help the practicing physician maintain the proper index of suspicion for recognizing carbon monoxide poisoning and providing the proper treatment for severe cases.