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Pineal parenchymal tumors of intermediate differentiation in adults: case report and literature review.

Pineal parenchymal tumors (PPT), including pineoblastomas, are very uncommon, especially in adults. Because of the small number of reported cases, the histological and biological features of these tumors are still being defined, as is their optimal management. Also, the pathological variability of these tumors makes it difficult to draw general conclusions about their behavior. We report the case of a PPT of intermediate differentiation (PPTID) with an excellent outcome. A 3.2 cm tumor in the pineal and tectal region with obstructive hydrocephalus was found in a 28-year-old female complaining of headaches and hypoesthesia of the right side of the face. Stereotactic biopsy revealed a highly cellular tumor composed of small cells that contained little cytoplasm that were arranged in a diffuse pattern. Mitotic activity was low and there was no evidence of necrosis. Immunohistochemical examination demonstrated positive staining for neuron-specific enolase and synaptophysin. There was no expression of neurofilaments or GFAP. Ki-67 proliferation index was 12%. The diagnosis was a PPTID. Treatment consisted of combined neoadjuvant chemotherapy and craniospinal radiotherapy. Six years after treatment, the patient is alive and free of any clinical or radiological signs of relapse. This paper discusses the pathological and biological features of these tumors and the treatment options available.

Adult↗

MR imaging in fibromatosis: results in 26 patients with pathologic correlation.

Fibromatoses are a diverse group of soft-tissue lesions that have been inconsistently categorized and treated. The purpose of our study was to establish the range of appearances of fibromatoses on MR images and perform a pathologic correlation to explain the variable signal-intensity patterns. During a 3-year period, 26 patients with deep fibromatoses were examined with MR. The MR images were evaluated for signal-intensity characteristics, and findings were correlated retrospectively with the pathologic diagnoses. The results showed that the MR appearance of fibromatoses is similar to that of other soft-tissue lesions, and the signal intensities vary greatly from lesion to lesion and within lesions themselves. The fibromatoses were either hyperintense, isointense, hypointense, or of mixed signal intensity relative to adjacent skeletal muscle. The hypointense areas appear to be zones of hypocellularity and dense collagen deposition. Microscopically all of the lesions invaded adjacent structures, but the MR appearances of the margins varied and were judged to be well demarcated (n = 14), intermediate (n = 5), or poorly demarcated (n = 6). Our experience shows that fibromatoses have a variable MR appearance no different from that of other soft-tissue lesions, and this variability reflects the composition and cellularity of the lesions.

Adult↗

Heart rate variability in children with obstructive sleep apnea.

Adults with obstructive sleep apnea syndrome (OSAS) display substantial heart rate changes associated with obstructive events, and recent reports suggest similar heart rate changes in children with OSAS. These rate changes could assist screening of young patients for OSAS. Six-hour polysomnographic recordings were obtained from seven children with OSAS (mean age: 4.5 years; apnea index: 19.5 +/- 5.1) and from seven primary snorers without OSAS who served as controls (mean age: 4.7; apnea index: 0). Scatterplots of each cardiac R-R interval against the preceding interval (Poincaré plots) were used to assess beat-to-beat cardiac variability at different heart rates. Beat-to-beat variation at slow rates was significantly increased in children with OSAS relative to controls, while variation at fast and intermediate heart rates was significantly reduced in these children. We conclude that OSAS alters beat-to-beat variation in characteristic fashions in children, that the variability changes occur at all heart rates but are most significant at slow heart rates, and that these heart rate patterns could assist in screening of suspected cases of OSAS.

Body Weight↗

Association between C-reactive protein and age-related macular degeneration.

CONTEXT: C-reactive protein (CRP) is a systemic inflammatory marker associated with risk for cardiovascular disease (CVD). Some risk factors for CVD are associated with age-related macular degeneration (AMD), but the association between CRP and AMD is unknown. OBJECTIVE: To test the hypothesis that elevated CRP levels are associated with an increased risk for AMD. DESIGN, SETTING, AND PARTICIPANTS: A total of 930 (91%) of 1026 participants at 2 centers in the Age-Related Eye Disease Study (AREDS), a multicenter randomized trial of antioxidant vitamins and minerals, were enrolled in this case-control study. There were 183 individuals without any maculopathy, 200 with mild maculopathy, 325 with intermediate disease, and 222 with advanced AMD (geographic atrophy or neovascular AMD). The AMD status was assessed by standardized grading of fundus photographs, and stored fasting blood specimens drawn between January 1996 and April 1997 were analyzed for high-sensitivity CRP levels. MAIN OUTCOME MEASURE: Association between CRP and AMD. RESULTS: The CRP levels were significantly higher among participants with advanced AMD (case patients) than among those with no AMD (controls; median values, 3.4 vs 2.7 mg/L; P =.02). After adjustment for age, sex, and other variables, including smoking and body mass index, CRP levels were significantly associated with the presence of intermediate and advanced stages of AMD. The odds ratio (OR) for the highest vs the lowest quartile of CRP was 1.65 (95% confidence interval [CI], 1.07-2.55; P for trend =.02). The OR for CRP values at or above the 90th percentile (10.6 mg/L) was 1.92 (95% CI, 1.20-3.06), and the OR for CRP values at or above the mean plus 2 SDs (16.8 mg/L) was 2.03 (95% CI, 1.03-4.00). A trend for an increased risk for intermediate and advanced AMD with higher levels of CRP was seen for smokers (OR, 2.16; 95% CI, 1.33-3.49) and those who never smoked (OR, 2.03; 95% CI, 1.19-3.46) with the highest level of CRP. CONCLUSION: Our results suggest that elevated CRP level is an independent risk factor for AMD and may implicate the role of inflammation in the pathogenesis of AMD.

Aged↗

Canopy photosynthesis and its relationship to plant productivity in near-isogenic cotton lines differing in leaf morphology.

A 2-year study was conducted to determine the relationships between plant canopy photosynthesis, canopy light interception, and plant productivity of cotton (Gossypium hirsutum L.) exhibiting differing leaf morphologies. The near-isogenic lines were from a single background (MD 65-11) and represented the leaf shapes Normal (small leaf lobing), Sub-Okra (intermediate leaf lobing), Okra (large leaf lobing), and Super Okra (severe leaf lobing). The F(1) of a cross Normal x Okra (intermediate leaf lobing) and the F(2) (segregating 1:2:1 for Normal Sub-Okra, and Okra, respectively) were also grown. Reduced plant canopies were produced by Okra and Super Okra lines, which translated into increased light penetration to the ground, and hence, in reduced canopy photosynthesis. Integrated canopy photosynthesis (ICAP) was significantly associated with light interception by the plant canopy. Part of the remaining variability in ICAP was associated with confounding factors associated with plant maturity and other unmeasured genotypic factors. Intermediate (F(1) and Sub-Okra) and normal leaf types displayed the largest ICAP values in both years. Lint production was positively related to ICAP (R(2) = 0.53). The combination of high ICAP values and competitive lint yields indicate that intermediate lobed leaf morphologies offer promise as productive sources of physiological variation for cotton germplasm development.

Journal Article↗

Localization of growth hormone-releasing factor-like immunoreactivity in the hypothalamo-hypophysial system of some teleost species.

An antiserum to growth hormone-releasing factor (GRF) 1-44 was applied on brain and pituitary sections of nine teleost species. Immunoreactive (ir) perikarya were demonstrated in parvo- and magnocellular portions of the preoptic nucleus (PON) and occasionally in the nucleus lateralis tuberis. The two tracts originating in the PON ran ventro-laterally toward the optic chiasm and then caudally in the basal hypothalamus. In the pars distalis (PD) of the eel, carp, goldfish and salmonids, GRF-ir fibers did not enter the rostral PD and few fibers passed close to somatotropes. In Myoxocephalus and Mugil, a variable number of ir-fibers passed close to cells of the rostral and proximal PD. In the neurointermediate lobe, GRF-ir fibers were located exclusively in the neural tissue of the eel and trout. In goldfish, carp and Myoxocephalus, GRF-ir fibers entered the intermediate lobe. This antiserum also labeled corticotrops and, to a lesser extent, melanotrops in the pituitary of cyprinids. A variable number of perikarya contained both GRF and vasotocin in the PON of the eel. In all teleost species studied so far, the distribution patterns of GRF are different, and the function of the various adenohypophysial cell types appears to be differently modulated, according to the variable distribution of GRF in the pituitary.

Anguilla↗

Effects of body condition score and score change on the reproductive performance of dairy cows: a meta-analysis.

A meta-analysis was conducted to evaluate the effects of body condition score (BCS) at parturition and at first AI, and of body condition change during the early lactation period on the variables pregnancy rate at first AI and number of days open in dairy cattle. Inclusion criteria for the publications were: comparison of at least two groups of animals of different categories of BCS or change (independent variables) and consideration of pregnancy rate at first AI or number of days open (dependent variables). Fifteen papers were selected and 23 excluded. Data corresponding to 7733 cows from 11 studies described in 10 papers were included in the analysis of pregnancy rate at first AI, and those derived from 4529 cows from 11 studies described in 10 papers were used to analyze effects on the number of days open. Analyses were stratified according to study design and milk production characteristics. We defined low, intermediate and high categories of BCS for values lower than 2.5, from 2.5 to 3.5, or higher than 3.5, respectively. The categories of body condition change were increase (gain in score), slight loss (0-0.5 point loss), moderate loss (0.6-1 point loss), and severe loss (over 1 unit loss). Intermediate body condition at parturition and at first AI, and a slight loss during the early lactation period were used as reference categories. The effects of body condition on the variable pregnancy rate at first AI were highly heterogeneous, while all the studies considering the number of days open presented homogeneous results. A clear association between body condition category and pregnancy rate at first AI was detected only when the effect of a low score at parturition was analyzed: pregnancy rate at first AI significantly decreased by about 10% in cows delivering in poor condition. Animals with a high BCS at parturition showed a significant reduction in the number of days open of 5.8 or 11.7 when compared with animals with an intermediate or low body condition, respectively. In animals in the high body condition category at first AI, the variable days open showed a significant drop of 11.9 or 24.1, compared to animals in the intermediate or low categories, respectively. A severe loss in score during early lactation was related to a significant (10.6) increase in the number of days open, while a slight or moderate body condition change, either loss or gain in score, was not significantly related to the variable days open. We found that the number of days open was a good indicator of the effects of BCS or change in score on reproductive performance in dairy cattle. The variable pregnancy rate at first AI, however, yielded heterogeneous results among studies.

Analysis of Variance↗

Monitoring of intrathecal oxygen tension during experimental aortic occlusion predicts ultrastructural changes in the spinal cord.

OBJECTIVE: To study the correlation between intrathecal PO2 and ultrastructural changes in the spinal cord during thoracic aortic occlusion in pigs. MATERIAL AND METHODS: In 18 pigs, online intrathecal oxygenation was monitored by a multiparameter Paratrend catheter (Biomedical Sensors, High Wycombe, United Kingdom) during 60 minutes' clamping of the proximal and distal descending thoracic aorta. The animals were randomly divided into 2 groups (A and B) depending on the level of distal aortic clamping. Distal aortic perfusion was restored through an aorto-iliac shunt, which also maintained low thoracic segmental perfusion of the spinal cord in group B. Perfusion-fixation technique was used before harvesting the spinal cord specimens, which later were evaluated with light and electron microscopy by an independent observer. Intrathecal parameters were interpreted as normal if PO2 was more than 0.8 kPa and PCO2 was less than 12 kPa, as intermediate ischemia if PO2 was 0.8 or less or PCO (2) was more than 12 kPa, and as absolute ischemia if PO2 was 0.8 or less and PCO2 was more than 12 kPa. RESULTS: Among 6 animals with ultrastructural changes of absolute spinal cord ischemia-reperfusion injury, 5 also had absolute ischemia according to variables derived by the Paratrend catheter. The 2 methods were in agreement in 3 of 5 animals with intermediate ischemia-reperfusion changes and in 5 of 6 animals with normal findings. The accuracy of cerebrospinal fluid PO2 and PCO2 to predict electron microscopy-verified intermediate or absolute ischemia-reperfusion injury was 94%. CONCLUSIONS: Monitoring of intrathecal PO2 after clamping of the descending aorta correlated with ultrastructural changes in the spinal cord in this pig model.

Animals↗

bcl-2 expression in the spectrum of preinvasive breast lesions.

BACKGROUND: The bcl-2 gene encodes for a protein that blocks apoptosis. Although the bcl-2 protein has been identified in some invasive breast cancers, its expression in preinvasive breast lesions has not been well characterized. METHODS: We studied bcl-2 expression using immunohistochemistry in cases of normal breast tissue (n = 10), ductal hyperplasia (n = 18), atypical ductal hyperplasia (ADH) (n = 10), atypical lobular hyperplasia/lobular carcinoma in situ (lobular neoplasia, LN) (n = 10), and ductal carcinoma in situ (DCIS) (n = 42). We also related bcl-2 expression to p53 expression in these lesions because the p53 gene is altered in many invasive breast cancers and is also involved in the regulation of apoptosis. RESULTS: bcl-2 was consistently expressed in the epithelial cells in all normal breast tissue, ductal hyperplasia, ADH, and LN lesions. In contrast, bcl-2 expression was present in 76% of the DCIS cases and was related to the histologic grade of DCIS. Staining for bcl-2 was observed in 100% of the well differentiated DCIS cases, 90% of intermediately differentiated cases, and 33% of poorly differentiated cases (P < 0.001). No immunoreactivity for the p53 protein was seen in any of the cases of normal breast tissue, ductal hyperplasia, ADH, or LN lesions. However, 24% of the DCIS cases were p53 positive. The bcl-2+/p53- phenotype, as seen in all cases of normal breast tissue, ductal hyperplasia, ADH, and LN was also observed in 67% of the DCIS cases. In contrast, the remaining 33% of DCIS cases showed combinations of bcl-2 and p53 expression that differed from that of normal breast epithelium and the other pathologic lesions studied. Most lesions with altered bcl-2/p53 phenotypes, including all bcl-2-/p53+ cases, represented examples of poorly differentiated DCIS. CONCLUSIONS: The bcl-2 protein is consistently expressed in normal breast epithelium, ductal hyperplasia, ADH, and LN. bcl-2 expression is variable in DCIS. Among DCIS cases, bcl-2 is most common in well differentiated and intermediately differentiated lesions. Most DCIS lesions are bcl-2+ and p53-, similar to normal epithelium, benign proliferative lesions, and LN. However, a minority of DCIS lesions show combinations of bcl-2 and p53 expression that differ from normal breast epithelium and from the other pathologic lesions studied. It is possible that such lesions may represent a subset of DCIS in which the regulation of apoptosis is no longer under normal control mechanisms, resulting in enhanced tumor cell survival and tumor growth.

Adult↗

Preparation and evaluation of zidovudine-loaded sustained-release microspheres. 2. Optimization of multiple response variables.

The formulation of zidovudine-loaded (AZT-loaded) sustained-release microspheres was prepared and optimized using response surface methodology. The objective was to use this statistical procedure to obtain a formulation with optimized overall properties. The effect of formulation variables (emulsifier concentration, drug to polymer ratio, and composition of the internal phase of the emulsion) on a number of response variables was systemically investigated. The response variables were t85, entrapment efficiency, yield, and percentage of loose surface crystals. A desirability function that combines these four response variables was constructed. A second-order polynomial equation was fitted to the data, and the resulting equation was used to predict the responses in the optimal region. All the investigated response variable were found to be highly dependent on the formulation variables, with strong interactions observed between the formulation variables. It was found that optimum overall desirability of AZT microspheres can be obtained at low levels of SDS and ethyl acetate concentrations and at intermediate levels of drug to polymer ratio. An optimized formulation was prepared under these experimental conditions and evaluated for individual responses and overall desirability. The experimental values of the response variables highly agreed with the predicted values.

Chemistry, Pharmaceutical↗

Long-term follow-up of intermediate uveitis in children.

PURPOSE: To analyze the clinical manifestations, remissions, and visual prognosis of intermediate uveitis in children, and to identify the risk factors for poor visual outcome. DESIGN: Retrospective cohort study. METHODS: Institutional study of 32 consecutive patients examined at a tertiary referral center with intermediate uveitis and the onset of ocular disease before the age of 16 years. Numerous variables were assessed, including age and gender distribution, laboratory data, the presence of systemic diseases, onset and course of ocular inflammation, clinical features and complications, therapeutic strategies and their outcomes, remission and final visual acuity, and characteristics associated with poor visual outcome. RESULTS: Bilateral involvement was observed in 94% of the patients. Remission was observed in seven out of 15 patients (47%) with completed follow-up of five years. For our 32 subjects, we found a mean time to remission of 6.4 years (SE 0.7, CI 5.1 to 7.7). Visual outcome was favorable as only three patients developed unilateral acuity of less than 0.1 after five-year follow-up, and no additional blind eyes manifested. No associated systemic diseases were established. Optic disk edema was the most frequent complication observed (71%). Cystoid macular edema (CME) was observed in 44% of the patients and was the most common cause of visual loss. CONCLUSIONS: Intermediate uveitis of childhood might exhibit a self-limiting course after several years. Visual loss was limited despite the high rate of severe ocular complications.

Adolescent↗

Durability of remission after ABMT for NHL: the importance of the 2-year evaluation point.

Few series describing the results of autologous bone marrow transplantation (ABMT) for the treatment of non-Hodgkin's lymphoma report mature follow-up. We retrospectively reviewed 110 adults with NHL treated with ABMT from 1988 to 1993. Overall survival and relapse-free survival were 50% and 35%, respectively. Estimated median relapse-free survival was 16 months. There was no statistically significant difference in relapse-free or overall survival by low, intermediate, and high-grade histologies, as defined by the International Working Formulation. The most powerful negative prognostic variable was an elevated LDH at the time of transplant (relapse-free survival 17% vs 42% for those with a normal LDH). Forty-seven patients were in complete remission 2 years after transplant. Extended follow-up revealed that 100% of patients with high-grade histologies remained in complete remission, whereas patients with intermediate-grade and low-grade histologies remained at risk of relapse with longer follow-up. Of 22 patients with diffuse large cell lymphoma (LCL) or immunoblastic (IBL) histologies, eight of eight with IBL remain in continued remission, while four of 14 with LCL relapsed 24-48 months after ABMT. We conclude that patients with high-grade histologic subtypes of NHL who are in complete remission 2 years after ABMT are likely to be cured. However, patients with intermediate and low-grade histologic subtypes are at continued risk of relapse and require appropriate clinical surveillance for at least 48 months after ABMT.

Adult↗

Typology of patient-patient assaults detected by videocameras.

OBJECTIVE: Previous studies of inpatient assault have relied on reports by ward staff, data from which are often incomplete. The authors observed patient-patient assaults with videocameras, obtaining previously unavailable data. In this article they report a systematic method for assault description and classification. METHOD: Assault was defined by behaviors such as hitting, kicking, and choking, with physical contact. Raters reviewed videotapes to make a global judgment of assailant intent to hurt; assault class was based on this judgment. At the same time the raters chose descriptors to better define classes. For external validation, the authors compared classes for resulting injuries, detection by incident reports, and patients' accounts of their motivations. RESULTS: Of 155 assaults detected, 21 were classified as least serious, 57 were in an intermediate group, and 76 were classified as most potentially hurtful. One assault could not be classified. Descriptor variables each made independent significant contributions to assault classification. Almost all assaults detected by incident report or resulting in injuries were in the most serious class. Assailants' claims that they were playing were significantly associated with the least serious class. CONCLUSIONS: With videocameras a variety of interactions between patients involving hitting, slapping, etc., were detected and documented. Some events seemed playful, others seemed intended to hurt, and some were of an intermediate type. This basic, descriptive work can lead to advances in the study of assault predictors.

Adolescent↗

Technical considerations in the immunohistochemical demonstration of intermediate filaments.

The intermediate filaments represent an important group of differentiation markers that have proven to be useful for the diagnosis and classification of human neoplasms. The immunohistochemical demonstration of these proteins is subject to numerous technical variables that include specificities and patterns of reactivities of polyclonal antisera and monoclonal antibodies, cross-reactivities of "specific" monoclonal antibodies with other intermediate filaments and other classes of antigens, masking of certain epitopes due to physiologic or pathologic changes in cells, effects of tissue fixation and subsequent tissue processing, and the sensitivity of the particular immunohistochemical detection system employed. Moreover, a wide variety of microenvironmental signals may affect the patterns of expression of intermediate filament proteins in different pathological conditions. For accurate interpretation of intermediate filament immunoreactivity, the pathologist must be familiar with the various sources of error relating to false positive or negative results. This requires the availability of optimally fixed tissues, a well-characterized set of antibodies to intermediate filament antigens and access to the results of extensive performance testing.

Antibodies, Monoclonal↗

Intersubject variability in perceived oscillation as a function of threshold for binocular disparity.

Four groups of 15 female subjects each were classified along a quantitative dimension for proportion of perceived oscillation and threshold for binocular disparity. Analyses of variance showed that significant differences in proportion of perceived oscillation were accompanied by significant differences in threshold for binocular disparity for perceivers of "high" and "low" oscillation (p less than .05). For perceivers of "intermediate" oscillation significant differences in proportion of perceived oscillation but not threshold for binocular disparity were found. It was suggested that: (1) intersubject variability in perceived oscillation may be governed by the threshold for binocular disparity, (2) "low" perceivers may be especially sensitive to the magnitude of the cue, (3) "intermediate" perceivers' subjective reports may be primarily dependent on response criteria and the multiplicity of subjective factors which constitute it, (4) "high" perceivers apparently have least response sensitivity and they cannot maintain a consistent response criterion.

Adolescent↗

Mutation analysis of patients with neuronal intermediate filament inclusion disease (NIFID).

Abnormal neuronal aggregates of alpha-internexin and the three neurofilament (NF) subunits, NFL, NFM, and NFH have recently been identified as the signature lesions of neuronal intermediate filament (IF) inclusion disease (NIFID), a novel neurological disease of early onset with a variable clinical phenotype including frontotemporal dementia, pyramidal and extrapyramidal signs. In other neurodegenerative diseases in which protein aggregates contribute to disease pathogenesis, mutations in the encoding protein cause the hereditary variant of the disease. To determine the molecular genetic contribution to this disease we performed a mutation analysis of all type IV neuronal IF, SOD1 and NUDEL genes in cases of NIFID and unaffected control cases. We found no pathogenic variants.

Adult↗

Quantification of human atrioventricular nodal concealed conduction utilizing S1S2S3 stimulation.

We studied antegrade concealed conduction of atrial extrastimuli (A2) that blocked in the atrioventricular (AV) node in eight subjects, using a third extrastimulus (A3), coupled at decreasing coupling intervals to A2. Three A1-A2 intervals were tested in each subject: late (just shorter than AV nodal effective refractory period), intermediate, and early (just longer than atrial functional refractory period). The curves relating the following variables were constructed for each A2: A1-A3, H1-H3 and A2-A3, A3-H3. The former was compared to the control A1-A2, H1-H2 curve. Concealment of A2 was demonstrated in all eight subjects at the three tested values of A1-A2. The A2-A3, A3-H3 curve allowed analysis of AV nodal conduction time (A3-H3) and AV nodal recovery time (defined as the shortest A2-A3 at which the impulse conducted to the His bundle) at identical values of A2-A3. In all subjects the timing of blocked A2 had minimal effect on both AV nodal conduction time and recovery time. In five of the eight subjects a late A2 sporadically conducted to the His bundle. Conduction of A2 to the His bundle resulted in marked lengthening of both AV nodal conduction and recovery times. Concealed conduction of A2 was always demonstrated, but the degree of concealment was relatively fixed, whether A2 was an early, intermediate, or late blocked premature beat. Slow conduction of A2 had a much greater effect than concealment of A2 on subsequent impulse conduction.

Aged↗

Mercury bioaccumulation in forage fish communities invaded by rainbow smelt (Osmerus mordax).

We compared total mercury concentrations ([Hg]) among 6 forage fish species in 25 central Canadian lakes and related [Hg] to adjusted-delta15N (an index of trophic position), delta13C, growth rate, and a suite of environmental variables. Growth rates were also compared among species and related to environmental variables. We found that rainbow smelt (Osmerus mordax), a recent invader in many of these lakes, had intermediate [Hg] and growth rates relative to other species. Forage fish growth rates differed significantly among species and were related to latitude (inverse relationship) and lake conductivity (positive relationship). Mercury concentrations also differed significantly among species and the strongest predictors were growth rate and lake conductivity; [Hg] was significantly and negatively related to both. Adjusted-delta15N explained very little variation in [Hg] and was significant only when the analysis was restricted to biotic variables. These results indicate that biomagnification may not be observed at fine scales of trophic differentiation and that rainbow smelt are unlikely to cause post-invasion [Hg] increases in most predatory fish species.

Animals↗