SPECT study of a German CADASIL family: a phenotype with migraine and progressive dementia only

OBJECTIVE: We describe the clinical, molecular, genetic, MRI, and SPECT features of a German family with autosomal dominant migraine and dementia, mapping to the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) locus. We studied the correlation of cerebral blood flow, MRI, and cognitive function. BACKGROUND: CADASIL is a small-vessel disease of the brain mapped to chromosome 19p13.1. Mutations of the Notch3 gene cause this disorder. Most phenotypes are characterized by transient ischemic attacks (TIAs) and lacunar strokes leading to dementia. Migraine is frequent. A single photon emission computed tomographic (SPECT) study of this disorder has not yet been published. METHODS: We studied 13 individuals clinically and performed neuroimaging studies with MRI and SPECT. RESULTS: Genetic analysis strongly supported linkage to the CADASIL locus, and the disease haplotype was found in six individuals. Analysis by single-strand confirmation polymorphism did not identify Notch3 mutations. All affected individuals had MRI white matter hyperintensities and four individuals had additional basal ganglial signal abnormalities. Four affected individuals had migraine, two of whom had slowly progressive dementia. TIAs, stroke, and focal neurologic signs were absent. Cerebral blood flow reduction in SPECT studies of affected individuals matched with MRI signal abnormalities. Cognitive impairment was linked to signal abnormalities and hypoperfusion in the basal ganglia. Demented patients had a pattern of frontal, temporal, and basal ganglial hypoperfusion. CONCLUSIONS: We describe a CADASIL phenotype that is characterized by the absence of focal neurologic symptoms and present the first SPECT study of this disorder.     

Cardiac rhabdomyosarcoma: a clinicopathologic and electron microscopy study

The use of imaging techniques including gamma scintigraphy to follow the behaviour of drug formulations has revolutionized our knowledge of absorption and distribution in drug delivery. The development of gamma camera techniques as physiological tools to explore organ function became routine by the mid-seventies. Several research groups started to explore the applications of technique in drug delivery. Within 5 years, the utility of the technique became obvious and scintigraphy is now widely accepted as an important investigation tool in formulation research. Gamma scintigraphy is especially useful in exploring sources of inter-subject variation, especially in examining food effects in pharmacokinetic estimations and establishing windows of absorption for oral delivery. As a tool to examine drug delivery to the lung and to the eye, scintigraphy is the method of choice. Magnetic Resonance Imaging (MRI) became more generally employed in medicine two decades after the gamma camera. The superior soft-tissue contrast and resolution compared to computed X-ray tomography rapidly established MRI in clinical investigation. Recent applications in oral drug research has allowed the pharmaceutical scientist to explore new facets of delivery and ultimately combine MRI and scintigraphy in human clinical trials.     

Reflux esophagitis in children: a scanning and transmission electron microscopy study

In children, excess of gastroesophageal reflux causes lesions of the esophageal mucosa that we have studied by scanning and transmission electron microscopy (SEM and TEM respectively) in 27 grasp biopsies prelevated during endoscopic procedures. Ultrastructural lesions can be graded on the basis of their severity. In grade I, epithelial cells are well preserved in the deepest layers whereas the superficial cells display ultrastructural alterations such as irregular microridges or reduced intercellular junctions. In grade II, the surface is composed of extruding cells and in the intermediate layer, large intercellular spaces containing lympho-monocytic cells are visible. In grade III, the mucosal surface is characterized by crater-like erosions, degenerating cells are visible in all the layers; in two patients columnar epithelium-lined areas (Barrett's esophagus) have been identified. Our results suggest that in patients with reflux esophagitis, ultrastructural examination of grasp biopsies prelevated by pediatric endoscopes allows a grading of the anatomical lesions providing data that can not be obtained by conventional histology.     

Differential diagnosis of decreased vision: a case study

Three patients who suffered transitory (from 18 to 49 days) cranial dyskinesias during the course of tubercular meningitis are described. The diagnosis was confirmed by the presence of acid-alcohol resistant bacilli in spinal fluid. Cranial tomography or magnetic resonance images failed to demonstrate anatomical lesions. The blink reflex and brain stem auditory evoked potentials were abnormal, indicating dysfunction of motor nuclei of the cranial nerves, possibly secondary to changes in their regulation by basal ganglia. No recurrences have been observed during follow-up (from 3 to 7 years).     

Laboratory diagnosis of keratomycosis: comparative evaluation of direct microscopy and culture results

We have studied the variation of lateral diffusion of proteins in the cell membrane, of membrane lipid fluidity and of the electrophoretic motility (EPM) of macrophages after treatment with extrinsic laminin. The results showed that the lateral diffusion coefficient D value of membrane proteins, the fluidity of membrane lipids and the EPM of macrophages were decreased after laminin had bound to its membrane receptor on the macrophages. These results are important for developing an understanding of the early reaction of plasma membranes and cells in the presence of laminin.     

Explosive cladding of Cu/Cu systems: An electron microscopy study and a thermomechanical model

Transmission electron microscopy investigations were carried out on three explosively cladded Cu/Cu systems: equiaxial small grains, elongated large grains and single crystals. The investigation has shown that the cladding process leads to the formation of a ‘bond zone’ rather than to a ‘planar interface’. The ‘bond zone’ independent of the cladding system could be divided into a few ‘cladding affected regions’ symmetrically extending on both sides of the colliding surfaces. Each of the regions is characterized by a definite structural morphology. Selected area diffraction patterns show that in all three systems, regions characterized by similar structures exhibit the same zone axis, namely 〈111〉 or 〈011〉. The ‘metallurgical bond’ achieved in the cladding process is constituted of small equiaxed recrystallized grains which form the center of the ‘bond zone’.The array of structures in the ‘bond zone’ as well as the dislocation densities result from a combination of three basic processes taking place during explosion cladding: mechanical (deformation), thermal and mass transfer.A theoretical model has been suggested for the treatment of the effects of the thermomechanical process on the annihilation of dislocations and their density distribution after cladding and on the extent of mass transport during transient annealing. The theoretically predicted results were compared with the experimental results obtained by means of transmission electron microscopy. For the Cu/Cu systems the agreement was found to be reasonable. The model presented should enable thermomechanical processes in other similar explosion clad systems to be treated.     

Demonstration of Chlamydia trachomatis in inguinal lymphadenitis of lymphogranuloma venereum: a light microscopy, electron microscopy and polymerase chain reaction study

Intravacuolar organisms in vacuolated macrophages were associated with areas of necrosis and suppuration in 12 patients with suppurative inguinal lymphadenitis. The intravacuolar organisms measured 0.2 to 2.0 micrometers in diameter, stained Gram negative with the Brown-Hopp's tissue Gram stain, faintly blue with hematoxylin and eosin stain, and black with the Warthin-Starry silver impregnation stain. The organisms lined vacuolar membranes and/or clumped in centers of vacuoles. Electron microscopy revealed elementary and reticulate bodies and intermediate forms characteristic of the genus Chlamydia. Cultures of three lymph nodes in McCoy cells grew Chlamydia trachomatis, lymphogranuloma venereum (LGV) serovars. Polymerase chain reaction using primers for chlamydial 16S ribosomal DNA confirmed the organisms as Chlamydia in lymph nodes from nine patients. Recognition of chlamydial organisms by light microscopy in tissue sections of lymph nodes allows a definitive diagnosis of lymphogranuloma venereum.     

Nickel and gold in skin lesions of pierced earlobes with contact dermatitis. A study using scanning electron microscopy and x-ray microanalysis

OBJECTIVE: To make an analysis of fungemia in HIV-infected patients in our hospital. PATIENTS AND METHODS: We retrospectively (1989-1997) studied all HIV-infected patients with positive blood cultures for Candida sp., Cryptococcus neoformans or any other fungal infection. RESULTS: C. neoformans was isolated in 11 patients (10 men and 1 woman): Six were treated with amphotericin B and 5 with fluconazole. 2 patients died during the acute phase and the infection relapsed in 3. Blood culture for Candida sp. were positive in 9 (8 men and 1 woman): only a case was nosocomial. Seven patients were intravenous drug users and the presenting manifestations were autolimited candidemia in 3, aortic and tricuspid endocarditis in 1 and 2 cases respectively and pneumonia in another one. Six C. albicans, 2 C. krusei and 1 C. glabrata were isolated. 3 patients received amphotericin B and 3 received fluconazole. 2 patients suffering from endocarditis died and so did the patient with C. glabrata infection. A patient, who denied having travelled to endemic areas, developed histoplasmosis; blood culture was positive for H. capsulatum. He initially had a good response to amphotericin B and itraconazole. CONCLUSIONS: Fungemia is not frequent in HIV-infected patients. Cryptococcosis and histoplasmosis occur in advanced HIV-patients and candidemia is fundamentally associated with intravenous drug use.     

Morphological and cytochemical investigation of human mesothelial cells from pleural and peritoneal effusions: a light and electron microscopy study

We investigated the morphological and cytochemical properties of mesothelial cells obtained from pleural and peritoneal effusions of patients with various diseases. The morphological features were studied by light and electron microscopy and by cytochemical methods. The different kinds of contact between mesothelial cells and their interaction with lymphocytes were observed and the transition of mesothelial cells to macrophages and/or fibroblasts was demonstrated.     

Decision tree in hematologic diseases: for a rationalization of histologic, phenotypic and genotypic diagnosis

The regulatory role of soluble cytokines in innate cellular immune responses induced by Pneumocystis carinii was assessed in vitro in direct comparison to induction by Listeria monocytogenes. This report shows that P. carinii organisms, as well as L. monocytogenes, stimulated in whole spleen cell cultures of SCID mice the release of IFN-gamma, TNF-alpha/beta, IL-10, IL-12, and iNO. This response was independent of functional T cells. Both macrophages (M phi) and natural killer (NK) cells were necessary for either microorganism to induce release of these cytokines. Cocultures of purified M phi--including alveolar M phi--and purified NK cells indicated that no other cell population was necessarily involved. Microbial induction of NK cell-derived IFN-gamma has been reported to be mediated by the combined effects of TNF-alpha and IL-12 released by M phi upon adequate microbial stimulation. Interestingly, only L. monocytogenes, but not P. carinii organisms could directly induce detectable amounts of TNF-alpha/beta, IL-12, or iNO in purified M phi cultures. In dose-response experiments, release of IFN-gamma, TNF-alpha/beta, and iNO was reduced at high relative concentrations of either microorganism. This high-dose suppression was at least partially controlled by M phi-produced IL-10. Our data show that, P. carinii potently induces activating and inhibitory innate cellular immune response mechanisms and indicate that the initial step of macrophage-mediated NK cell activation might also involve other pathways than those described to date.     

Progressive multifocal leukoencephalopathy in AIDS: a clinicopathologic study and review of the literature

We reviewed the clinical, radiographic, and pathologic features of 15 patients with the acquired immune deficiency syndrome (AIDS) and progressive multifocal leukoencephalopathy (PML). Brain tissue from 10 autopsy and 6 biopsy specimens was studied using: in situ hybridization (ISH) for JC virus (JCV), immunohistochemistry for human immunodeficiency virus (HIV) p24 antigen, and electron microscopy. Thirteen patients presented with focal neurologic deficits, while 2 presented with a rapid decline in mental status. PML was commonly the initial opportunistic infection of AIDS and produced hemiparesis, dementia, dysarthria, cerebellar abnormalities, and seizures. Magnetic resonance imaging was more sensitive than computed tomography in detecting lesions, and often showed multifocal areas of PML. CD4+ T-cell counts were uniformly low (mean 84/mm3), except in 1 patient who improved on 3'-azido-3'-deoxythymidine (AZT). PML involved the cerebral hemispheres, brain stem, cerebellum, and cervical spinal cord. The distribution of brain involvement was consistent with hematogenous dissemination of the virus. In 2 brain specimens, multiple HIV-type giant cells were present within the regions involved by PML. When co-infection by HIV and papovavirus was present, PML dominated the pathological picture. ISH for JCV showed virus in the nuclei of oligodendrocytes and astrocytes. Occasionally there was staining for JCV in the cytoplasm of glial cells and in the neuropil, the latter possibly a correlate of papovavirus spread between myelin sheaths, as seen by electron microscopy. ISH demonstrated more extensive foci of PML than did routine light microscopy.     

Substance use diagnosis within a community sample of adults: Distinction, comorbidity, and progression over time.

Practicing psychologists conceptualize, assess, and treat clients who use substances in different ways. Using longitudinal data from a multiethnic community sample of 470 adults, the authors examine patterns of abuse and dependence on alcohol, marijuana, and cocaine. Men were significantly more abusive, dependent, and polysubstance dependent on all drugs than women. A large percentage of drug abusers, and over 1/3 with drug dependence, remitted without formal treatment. However, early severe problems with cocaine increased later alcohol problems. Traditional disease progression and drug use acquisition models are not supported. Psychologists should incorporate the natural course of substance use into treatment and prevention efforts. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The use of transbronchial lung biopsy to establish a diagnosis of benign clear cell tumor of the lung: report of a case

Benign clear cell tumor (BCCT) is an extremely rare pulmonary neoplasm. We report herein a case of BCCT of the lung that was diagnosed by a transbronchial lung biopsy (TBLB). The findings of hematoxylin-eosin and immunohistochemistry obtained by the TBLB were consistent with a diagnosis of BCCT of the lung. Wedge resection was subsequently performed by video-assisted thoracotomy. To the best of our knowledge, this is the first reported case of BCCT diagnosed by TBLB.     

Scanning electron microscopy and histologic analysis of an apexification "cap": a case report

Hemophagocytic lymphohistiocytosis (HLH), also referred to as familial erythrophagocytic lymphohistiocytosis, is a rare disorder of infancy associated with proliferation of activated histiocytes and T cells, anemia, thrombocytopenia, and fevers. This disorder appears to be due to the uncontrolled activation of T cells producing IL-2, tumor necrosis factor-alpha, and interferon-gamma. Untreated, the disorder is universally fatal. Various deficits in immune function have been described during acute disease activity including impaired T cell function, impaired monocyte-mediated antibody-dependent cytotoxicity, impaired natural killer cell function, and impaired IL-1 production. We examined natural killer cell function in familial HLH patients to determine whether this finding was consistently associated with the disease. We also examined natural killer cell function in asymptomatic parents and siblings of patients. Impaired natural killer cell function was identified in all patients and in some family members, including obligate carrier parents. This implies that one potential genetic defect in HLH may result in depressed natural killer function, but that this may not be sufficient to reliably predict eventual progression to disease.     

Mesotheliomas of tunica vaginalis testis of Fischer 344 (F344) rats treated with acrylamide: a light and electron microscopy study

It is known that there are large temperature elevations in proximity to air bubbles during US (ultrasound) heating. The existence of tiny air bubbles in the target tissue may enhance the temperature elevation in US hyperthermia. To examine this hypothesis, phantom tissue experiments using an US contrast agent consisting of tiny air bubbles surrounded by a 5% (w/v) human albumin shell (Alb) were performed. As a phantom tissue, a 2 cm cube of beef was used. The phantom tissue was heated with or without the US contrast agent by an US hyperthermia device for 3 min. The heating device was operated at 1.5 MHz with the US intensity of 0.9 W/cm2. Physiological saline solution, iodized oil, and ethanol were used for control experiments. The effect of multiple needle punctures to the beef phantom was also examined. The temperature elevation rate (TER) was defined as the ratio of temperature elevation by heating with Alb or control materials to the temperature elevation by US heating alone. The TER of Alb was 1.7, whereas the TERs of the control materials and of the multiple needle punctures were approximately 1. The administration of Alb significantly increased the temperature in US hyperthermia. In addition, the heating efficiency of Alb was compared to the effect of an increase in the US intensity. Phantom tissue was heated at various US intensities. When the US intensity was increased from 0.9 to 1.8 W/cm2, the temperature elevated by approximately 1.7-fold. Thus, the effect of the administration of Alb was almost equivalent to the effect of increase in US power intensities from 0.9 to 1.8 W/cm2 in the present experimental settings. The results suggest that the US contrast agent can be a potential enhancer in US hyperthermia.     

Microarchitecture of the cat testis with special reference to Leydig cells: a three-dimensional study by alkali maceration method and scanning electron microscopy

Testes from adult cats were studied by means of parallel transmission and scanning electron microscopy (SEM) after NaOH digestion technique, which selectively removed connective tissues or cells. The testis is covered by a dense fibroconnective tunica albuginea that partially divides the organ in lobules by sending septa into the parenchyma. The lamina propria of the seminiferous tubules consisted of one or two rows of cells. The interstitium was made up of randomly arranged collagen bundles. The most significant feature was the numerous Leydig cells rich in lipid droplets and displaying epithelioid features. Following alkali digestion and SEM these cells showed a cord-like arrangement. The cords were formed by one or two closely apposed cells, in between which some labyrinthine or canalicular-like spaces were left that in some areas opened in wide perivascular spaces. This particular arrangement of Leydig cells and the labyrinthine intercellular spaces is very likely designed to improve cell secretion of hormones, facilitating their transport into the blood, as well as the traffic of fluids and metabolites. The present techniques allowed the visualization of a real three-dimensional testicular microarchitecture and microtopography, not detectable with other methods. Such a study may help to better highlight the testicular morphophysiology.     

Cerebral cortex blood flow and vascular smooth muscle contractility in a rat model of ischemia: a correlative laser Doppler flowmetric and scanning electron microscopic study

The present study was undertaken to ascertain the role of smooth muscles and pericytes in the microcirculation during hyperperfusion and hypoperfusion following ischemia in rats. Paired external carotids, the pterygopalatine branch of the internal carotids and the basilar artery were exposed and divided. Reversible inflatable occluders were placed around the common carotids. After 24 h, the unanesthetized rat underwent 10-min ischemia by inflating the occluders. Continuous cortical cerebral blood flow (c-CBF) was monitored by laser Doppler flowmetry. The measured c-CBF was below 20% of control (P < 0.001) during ischemia. A c-CBF of 227.5 +/- 54.1% (P < 0.001) was obtained during reperfusion hyperemia. A c-CBF of 59.7 +/- 8.8% (P < 0.001) occurred at the nadir of postischemic hypoperfusion, and this was followed by a second hyperemia. The cytoarchitecture of the vascular smooth muscles and pericytes was assessed by scanning electron microscopy. Samples were prepared using a KOH-collagenase digestion method. In control rats, arteriolar muscle cells showed smooth surfaces. Capillary pericytes were closely apposed to the endothelium. Immediately after reperfusion, transverse membrane creases were observed on the smooth muscle surfaces. During maximal hyperemia the creases disappeared. When c-CBF started to decrease the creases became visible again. Throughout the postischemic hypoperfusion the creases remained. Capillary endothelial walls became tortuous in the late phase of hypoperfusion. During the second hyperemia most arteriolar muscle cells showed smooth surfaces. Some pericytes appeared to have migrated from the vascular wall. The morphological changes of smooth muscle membranes suggest that they are related to specific perfusional disturbances during ischemia and reperfusion.     

Phytosterolaemia in a Norwegian family: diagnosis and characterization of the first Scandinavian case

Phytosterolaemia (sitosterolaemia) is a very rare inherited sterol storage disease characterized by tendon and tuberous xanthomas and by a predisposition to atherosclerosis. We here describe the first Scandinavian case. The 14-year-old female patient was found to have markedly elevated circulating levels of plant sterols (sitosterol, sitostanol, campesterol, stigmasterol), and the levels of these sterols were 20-50 times higher than in her healthy sister and heterozygous parents. In addition to the usual serum plant sterols we found a new major sterol in the patient tentatively identified as episterol or fecosterol (24-methyliden-cholest-7 (or 8)-en-3 beta-ol). A newly developed method based on the use of deuterium labelled cholesterol and plant sterols was used to measure sterol absorption in the patient and her relatives. Absorption of sitosterol averaged 20% in the patient and ranged from 4 to 8% in the relatives. Absorption of campesterol averaged 31% in the patient and ranged from 15 to 18% in her relatives. Absorption of cholesterol averaged 63% in the patient and ranged from 35 to 45% in the relatives. Cholesterol synthesis appeared to be reduced in the patient and was 46-52% of that of her relatives.     

X-ray and transmission electron microscopy investigation of strain in a nitrided steel: No evidence of plastic deformation

In order to characterize the nitrided layers of steels, the X-ray diffraction (XRD) technique has been used coupled with transmission electron microscopy (TEM) observations. The TEM observations of the nitrided layers were made using a cross-sectional specimen preparation technique. Using the Warren-Averbach approach to the analysis of the diffraction peak broadening and TEM investigations, the existence of several precipitates of nitrides was brought to the fore, but no evidence for dislocations was found. To improve the calculation of the Fourier coefficient, the diffraction peaks were described in reciprocal lattice by a mixed Cauchy-Gauss curve. In fact, our investigations show that the broadening of the diffraction peaks of nitrided layers is strongly dependent on the size of the coherently diffracting domains. For nitriding, this result confirms that the residual stresses are only attributable to the precipitation of nitrides. In contrast, the microstructural state obtained after mechanical surface treatments, such as shot peening, is very different; the incompatibility of the plastic strains is the origin of the stress field.     

X-ray and transmission electron microscopy investigation of strain in a nitrided steel: No evidence of plastic deformation

In order to characterize the nitrided layers of steels, the X-ray diffraction (XRD) technique has been used coupled with transmission electron microscopy (TEM) observations. The TEM observations of the nitrided layers were made using a cross-sectional specimen preparation technique. Using the Warren-Averbach approach to the analysis of the diffraction peak broadening and TEM investigations, the existence of several precipitates of nitrides was brought to the fore, but no evidence for dislocations was found. To improve the calculation of the Fourier coefficient, the diffraction peaks were described in reciprocal lattice by a mixed Cauchy-Gauss curve. In fact, our investigations show that the broadening of the diffraction peaks of nitrided layers is strongly dependent on the size of the coherently diffracting domains. For nitriding, this result confirms that the residual stresses are only attributable to the precipitation of nitrides. In contrast, the microstructural state obtained after mechanical surface treatments, such as shot peening, is very different; the incompatibility of the plastic strains is the origin of the stress field.