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PubMed2000

Macrophages synthesize factor X and secrete factor X/Xa-containing prothrombinase activity into the surrounding medium.

Activation of the coagulation cascade, mediated by various monocyte/macrophage procoagulants, is an important component in the pathology of inflammatory disease. The type of procoagulant expressed may vary between different monocyte/macrophage subtypes and may differ depending on how the cells are treated. In the present study we show that both murine peritoneal macrophages and human adherent synovial cells from rheumatoid arthritis lesions express prothrombinase activity that was inhibited by anti-Factor X antibodies. Northern blot analysis showed that Factor X was transcribed by the murine peritoneal cells and Western blot analysis showed the presence of Factor X antigen. Further experiments showed that the prothrombinase activity was secreted by the cells into the medium in a detergent-sensitive form, suggesting that the prothrombinase is released on small lipid-containing vesicles.

Animals↗

PubMed2001

Stimulation of endothelin B receptors in astrocytes induces cAMP response element-binding protein phosphorylation and c-fos expression via multiple mitogen-activated protein kinase signaling pathways.

The vasoconstrictor peptide endothelin (ET-1) exerts its physiological and pathological effects via activation of ET(A) and ET(B) receptor (ET-R) subtypes. In this study, we demonstrate that both ET-R subtypes are highly expressed in rat astrocytes in vivo, indicating that these cells are potential targets of the biological effects of ET-1 in the brain. In cultured cortical astrocytes, both ET-R subtypes are expressed, and selective stimulation of ET(B)-R with ET-1 induces phosphorylation of cAMP response element-binding protein (CREB). The signal transduction pathway activated by ET-1 includes the Rap1/B-Raf and the Ras/Raf-1 complexes, protein kinase C (PKC) together with extracellular signal-regulated kinases (ERK), and the ribosomal S6 kinase (RSK) isoforms RSK2 and RSK3, two kinases that lie immediately downstream of ERK and are able to phosphorylate CREB. Moreover, ET-1 activates the p38 mitogen-activated protein kinase (MAPK)-dependent, but not the c-jun N-terminal kinase (JNK)-dependent pathway. By using selective protein kinase inhibitors and expression of dominant-negative Rap1 protein, we also found that the Rap1/PKC/ERK-dependent pathway induces the phosphorylation of activating transcription factor-1, CREB, and Elk-1, whereas the p38MAPK-dependent pathway only causes CREB phosphorylation. ET-1-induced transcription of the immediate early gene c-fos requires the concomitant activation of both the PKC/ERK- and p38MAPK-dependent pathways, because inhibitors of either pathway block the ET-1-induced increase of c-fos mRNA. Our findings indicate that changes in the expression of cAMP response element-dependent immediate and delayed response genes could play a pivotal role in the physiological effects elicited by ET-1 in astrocytes.

Activating Transcription Factor 1↗

PubMedDate not supplied

The sentinel lymph node in papillary cancer of the thyroid including histological subtype.

BACKGROUND: The aim of this work was to reveal through sentinel node study the intraoperative presence of preoperatively undetected pathological lymph nodes. MATERIALS AND METHODS: At the Surgical Science Department of La Sapienza University of Rome The Authors studied from January 2003 to June 2004 18 patients with papillary carcinoma of the thyroid, who presented no clinical evidence of lymph node metastasis; they performed a total thyroidectomy in all cases, removing and histologically examining all lymph nodes of the upper anterior mediastinum. Where negative they were then subjected to immunohistochemical analysis with Pan Cytokeratin. RESULTS: The method was positive in 10 patients: 2 pure papillary carcinomas, 1 papillary carcinoma with poorly differentiated areas, 1 tall cell papillary carcinoma, 5 sclerosing carcinoma and 1 follicular variant papillary carcinoma; and negative in 8:5 pure papillary carcinomas, 2 sclerosing carcinoma and 1 case of follicular variant papillary carcinoma. Lymph node micrometastasis was found in 2 cases through study with Pan Cytokeratin on final histological examination. CONCLUSIONS: Analysis of the Authors' preliminary data shows that sentinel lymph node detection has 83.3% sensitivity and 100% specificity for Upper Anterior Mediastinum lymph nodes. The Authors can propose two main applications: select for dissection only patients with a positive sentinel node and reduce the number of cases to be subjected to postoperative treatment with iodine ablation, in patients with "low risk" thyroid tumours and negative sentinel nodes.

Adult↗

PubMed1988

[Glial fibrillary acidic protein and neurofilament protein in medulloblastoma].

Medulloblastoma is the most common primitive neuroectodermal tumor (PNET) with the potential to differentiate along glial or neuronal lines. Thirty cases of medulloblastoma were tested by the peroxidase-antiperoxidase (PAP) method with anti-GFAP serum (DAKO) and by the avidin-biotin peroxidase complex (ABC) method with 68kd subunit of anti-NF antibody. All the cases were classified into three subtypes based on these immunohistochemical findings and were analyzed in relation to clinico-pathological features. Fifteen of thirty medulloblastomas contained GFAP positive cells, seventeen showed cells reacting to NF. The reactions for both proteins were present in eight medulloblastomas (PNET-BD, bipotential differentiation). Seventeen medulloblastomas reacted to only one protein (PNET-MD, monopotential differentiation). No reaction for either was found in five cases (PNET-NOS, not otherwise specified). The two year survival rate was 12.5% for PNET-BD compared to 49.2% for PNET-MD and 53.3% for PNET-NOS. Nine variables, i.e. age, tumor stage, metastatic stage, operation, radiotherapy, chemotherapy, histology, GFAP and NF, were analyzed using Cox's proportional hazard model. This revealed that the significant factors were tumor stage (p = 0.0002), GFAP (p = 0.0008) and operation (p less than 0.05). In conclusion, GFAP is the most important histological factor for prognosis and medulloblastoma without glial differentiation has a much better prognosis than one with glial differentiation.

Adolescent↗

PubMed1995

The low-grade glioma debate: evidence defending the position of early radiation therapy.

From the preceding supporting evidence, the following conclusions can be drawn: Supratentorial LGGs are a pathologically diverse group of CNS neoplasms whose natural history is primarily dependent upon histologic subtypes. The observed survival of all histologic subtypes of supratentorial LGGs are statistically significantly worse than that of an age- and sex-matched control population. Moderate-dose postoperative RT appears to improve survival in, and may cure, a subset of patients with supratentorial nonpilocytic LGG, particularly in those in their 30s and older. Multiple shaped localized treatment fields should be utilized because whole brain radiation is both unnecessary and associated with greater toxicity. Patients with supratentorial LGGs are usually neurologically "intact" but do exhibit cognitive impairment. Neurologic, functional, cognitive, and affective status do not appear to be negatively impacted by modern postoperative RT in adults with supratentorial LGG. Therefore, all adult patients with histologically verified supratentorial low-grade nonpilocystic astrocytomas (diffuse fibrillary astrocytoma, mixed oligo-astrocytoma, or oligodendroglioma) should routinely receive postoperative RT. Localized treatment fields should be employed. The optimum dose of radiation within the range of 4,500 to 6,480 cGy has yet to be determined.

Astrocytoma↗

PubMed2002

Cerebral amyloid angiopathy and cognitive function: the HAAS autopsy study.

OBJECTIVE: To investigate the relationship between cerebral amyloid angiopathy (CAA), dementia, and cognitive function in an autopsy sample of 211 Japanese-American men from the population-based Honolulu-Asia Aging Study. METHODS: Starting in 1991, participants were assessed with the Cognitive Abilities Screening Instrument (CASI) and diagnosed with dementia (including subtype) based on published criteria. At autopsy, neuropathologists blinded to clinical data examined brains for neurofibrillary tangles (NFT), neuritic plaques (NP), and a number of vascular pathologies, including CAA. CAA was detected by immunostaining for betaA4 amyloid in parenchymal vessels in the neocortex and semiquantitatively rated. Linear regression models were used to examine the association of CASI score, dementia subtype, and CAA controlling for age at death, time between CASI administration and death, education, NP and NFT counts, infarcts, hemorrhage, and APOE genotype. RESULTS: A total of 44.1% of subjects had CAA in at least one neocortical area. The presence of CAA was associated with higher mean NFT and NP counts and having at least one APOE-epsilon4 allele. The interaction between CAA and AD on the adjusted mean CASI score was significant; compared with nondemented men without CAA, the CASI score was 16.6% lower in men with AD and no CAA and 45.9% lower in men with AD plus CAA. CONCLUSIONS: CAA may contribute to the clinical presentation of dementia by interacting with other neuronal pathologies, leading to more severe cognitive impairment in men with both CAA and AD compared with men with only AD or CAA.

Aged↗

PubMed1998

Urinary levels of chemokines (MCAF/MCP-1, IL-8) reflect distinct disease activities and phases of human IgA nephropathy.

Leukocytes have been implicated to be involved in the pathogenesis of IgA nephropathy (IgAN). To clarify the precise molecular mechanism of recruitment and activation of leukocytes in the subgroups of IgAN, latent, acute, and chronic types, we studied monocyte chemotactic and activating factor (MCAF/MCP-1) and interleukin (IL)-8 in urines and renal expression of these cytokines. Urinary MCAF levels were significantly higher in chronic type, and were correlated with pathological progressive factors such as mesangial proliferation and interstitial cellular infiltration associated with CD68-positive macrophage. On the other hand, urinary IL-8 elevated only in acute type and were correlated with glomerular endocapillary proliferation and the degree of hematuria. In immunohistochemical study, IL-8 was mainly observed in glomeruli, otherwise MCAF in vascular endothelial cells, tubular epithelial cells, and infiltrated mononuclear cells in the interstitial lesions. These observations demonstrated that MCAF and IL-8 were differentially expressed in kidneys with IgAN, and their subtypes, and suggest that chemokines may be involved in the pathogenesis of IgAN at distinct phases or pathological lesions, possibly through the recruitment and activation of a distinct type of leukocyte.

Adolescent↗

PubMed1999

[Typification of strains of Helicobacter pylori by the detection of the cagA gene and subtypes of the vacA gene].

BACKGROUND: Helicobacter pylori infection is probably the most common chronic bacterial infection in the world. The consequences of infection are pathologies like peptic ulcer, chronic gastritis, gastric cancer and gastric MALT lymphoma. The aim of this study was to detect the vacuolating cytotoxin gene (vacA) type, the cytotoxin-associated gen (cagA) of H. pylori isolates and study their association with the vacuolising activity. MATERIAL AND METHODS: Gastric biopsy specimens were obtained from dyspeptic patients. Isolates were further genotypically typed by PCR. RESULTS: All strains studied were vacA+ and 55% were cagA+. All cytotoxic strains were cagA+, subtype vacA s1/m1 and corresponded to patients with peptic ulceration. The cagA- strains (11) corresponded to subtype s2/m2. We didn't demonstrate vacuolising activity on subtypes s1/m2 and s2/m2. CONCLUSIONS: A high genetic diversity exists among strains in our environment. The subset of bacteria, vacA s1/m1/cagA+, is associated with vacuolising activity in culture cells (tox+).

Adult↗

PubMed2006

Role of carbonic anhydrases in the progression of renal cell carcinoma subtypes: proposal of a unified hypothesis.

Renal cell carcinoma (RCC) has the highest rate of occurrence within the US when compared with other countries. Recent advances in the basic research and molecular diagnostics of this malignancy have revealed that RCC is not a single disease, but it is a mixture of several types of malignancies with unique molecular mechanisms and pathological attributes. RCC is now divided into clear cell carcinoma (80% of all kidney cancers), papillary type 1 and papillary type 2 neoplasms (10-15% of all RCC patients) and RCC with chromophobic and oncocytic features, called the Birt-Hogg-Dube (BHD) subtype, in roughly 5% of all patients. Apart from these, neoplasms such as the tuberous sclerosis (TSC) syndrome may occur with a mixed pathological features with a renal presentation. In this review, molecular evidence, both direct and indirect, published so far on all these RCC subtypes have been analyzed to find out whether there is any common thread that could run through these disparate malignancies that happen to occur in a single organ, i.e., the kidney. We believe that the role played by the expression and certain non-traditional activities of the cabonic anhydrase (CA) family members, along with the differing levels of hypoxia induced within these tumors may be the most common denominators. Evidence is presented focusing on how the CA family members could participate in the genesis and progression of each and every one of these RCC subtypes and how their function could be influenced by hypoxia, activities of receptor type protein tyrosine kinases and certain other pre-disposing factors. These rationalizations point towards a unified hypothesis that may help explain the occurrence of all these RCC subtypes in a molecular manner. We hope that these analyses would a) stimulate further studies aimed toward a better understanding of the role played by carbonic anhydrases in RCC subtypes and b) would pave way to a better and rationally designed therapies to interfere with their function to benefit patients with RCC and possibly other cancers.

Carbonic Anhydrases↗

PubMed2001

Malignant thymic epithelial tumors: CT-pathologic correlation.

OBJECTIVE: The purpose of our study was to describe and compare the CT and pathologic findings of atypical thymoma and thymic carcinoma. MATERIALS AND METHODS: Twenty-seven consecutive patients (14 men, 13 women ranging in age from 22 to 77 years [mean age, 52 years]) with pathologically proven atypical thymoma (n = 9) and thymic carcinoma (n = 18) constituted the study population. The chest CT findings in each of the 27 patients were reviewed retrospectively in consensus by two chest radiologists. These findings were correlated with pathologic findings. RESULTS: The tumors were located in the anterior mediastinum, and most tumors had a lobulated margin (24/27, 89%). Atypical thymomas were significantly smaller (mean, 4.7 cm) than thymic carcinomas (mean, 7.2 cm) (p = 0.041) on CT. The findings of invasion of the great vessels, lymph node enlargement, extrathymic metastases, and phrenic nerve palsy were seen only in patients with thymic carcinoma. The frequencies of necrosis, intratumoral calcification, pleural effusion, pleural implants, pericardial effusion, and obliteration of the mediastinal fat plane were not significantly different between atypical thymomas and thymic carcinomas (p > 0.05). Various histologic subtypes were included in thymic carcinoma. The tumor necrosis and calcification seen on CT were confirmed at pathologic examination. CONCLUSION: When a large thymic tumor appears with invasion of the great vessels, lymph node enlargement, phrenic nerve palsy, or extrathymic metastases on CT, thymic carcinoma rather than atypical thymoma should be considered.

Adult↗

PubMed2003

Actions of Group I and Group II metabotropic glutamate receptor ligands on 5-hydroxytryptamine release in the rat cerebral cortex in vivo: differential roles in the regulation of central serotonergic neurotransmission.

We have previously shown that the release of central neurotransmitters can be modulated by the activation of Group I and Group II subtypes of G-protein-linked metabotropic glutamate (mGlu) receptors. To date, however, very little is known about the regulation of serotonergic neurotransmission by these receptor subtypes. In the present study, we have utilized in vivo intracerebral microdialysis to elucidate the roles of Group I and Group II mGlu receptors in the regulation of neuronal 5-hydroxytryptamine (5-HT) release in the frontal cortex of conscious, freely moving rats. Dialysate 5-HT was of neuronal origin with basal release showing strong calcium dependency and tetrodotoxin sensitivity and marked elevation following K(+)-induced depolarization. The broad-spectrum mGlu receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD; 1-3 mM] did not significantly modify basal cerebrocortical 5-HT release. Similarly, the Group I mGlu receptor-specific agonist (RS)-3,5-dihydroxyphenylglycine [(RS)-3,5-DHPG; 1-3 mM] showed no marked effect on cortical dialysate 5-HT levels. To eliminate the possibility that these findings were the result of receptor desensitization, the effects of lower concentrations of (RS)-DHPG (100-300 microM) and shorter ligand exposure time (15 min) were also evaluated. Dialysate 5-HT levels remained unmodified by these manipulations. In comparison, the Group II mGlu receptor agonist, (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-1; 500 microM), evoked a marked facilitation of release (approximately 150% of basal) which was fully reversed by the Group I/II antagonist, (S)-alpha-methyl-4-carboxyphenylglycine [(S)-MCPG; 3 mM]. The modulatory action of L-CCG-1 showed a bell-shaped concentration-response relationship. (S)-MCPG (3 mM) and the potent and selective mGlu(5) receptor antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP; 100 microM), when given alone, did not significantly modify 5-HT levels.The current data provide strong evidence to suggest that while the release of neuronal 5-HT in the rat frontal cortex is not subject to regulation by facilitatory Group I mGlu receptors, it may be positively modulated by activation of Group II mGlu receptors. Taken together with data from other studies, the present investigation lends emphasis to the notion that neuromodulation by mGlu receptors is a region-specific phenomenon and also proposes that the heterogeneous distribution of these receptors is neurone-specific in its complexity. The failure of (S)-MCPG alone to modify cortical 5-HT release suggests that Group II mGlu receptors do not tonically modulate serotonergic neurotransmission in the cerebral cortex but this does not preclude an important functional role for these receptors during pathological conditions when endogenous neurotransmitter levels become excessively elevated. The strategic development of new subtype-specific mGlu receptor ligands may provide novel therapeutic agents for the treatment of a range of neurological and psychiatric disorders.

Amino Acids, Dicarboxylic↗

PubMed2004

Histology in mixed germ cell tumors. Is there a favorite pairing?

PURPOSE: Mixed germ cell tumors account for approximately 30% to 50% of testicular tumors. To our knowledge a systematic review with statistical analysis of the associations of histological subtypes in mixed germ cell tumors has not been done previously. It was our impression that such associations exist. Delineating concordant histological types may provide insight into the ontogeny of testicular tumors and also have important clinical implications. MATERIALS AND METHODS: We retrospectively reviewed the testis cancer data base at our institution. The primary tumor of orchiectomy specimens was examined in 2589 patients. Of these patients mixed histology was noted in 1765 (68.2%). ORs were calculated for all possible combinations of teratoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma and seminoma. In addition, we evaluated the association of various histological types with teratoma at post-chemotherapy retroperitoneal lymph node dissection. RESULTS: Of 10 possible combinations of histological types in the primary tumor, positive correlations were noted in 4. The strongest correlation was found between teratoma and yolk sac tumor (OR 2.58, p <0.001). Teratoma or yolk sac tumor in the testis was associated with teratoma in the pathology specimen at post-chemotherapy retroperitoneal lymph node dissection. CONCLUSIONS: The strongest associations of histological subtypes in mixed germ cell tumors were seen between yolk sac tumor and teratoma. Similar associations are seen in late relapse and in some cases of prepubertal tumors. Further study of these associations may prove valuable in understanding the biology and clinical behavior of germ cell tumors.

Germinoma↗

PubMed2026

Subtype-specific clinical significance of RRM1 and RRM2 expression in non-small cell lung cancer: a TCGA-based analysis.

BACKGROUND: Non-small cell lung cancer (NSCLC), including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), exhibits significant molecular heterogeneity. Ribonucleotide reductase (RNR), composed of RRM1 and RRM2, is essential for DNA synthesis and repair, but its subtype-specific clinical significance in NSCLC remains unclear. OBJECTIVE: To investigate the clinical and prognostic significance of RRM1 and RRM2 expression in NSCLC, with a focus on subtype-specific differences between LUAD and LUSC. METHODS: We analyzed RNA expression and clinical data from 980 NSCLC patients in The Cancer Genome Atlas (TCGA). Associations with clinicopathologic characteristics, overall survival, and oncogenic driver alterations were assessed. RESULTS: In LUAD, high RRM2 expression was significantly associated with advanced pathologic stage (p = 0.004), nodal involvement (p = 0.005), higher T stage (p = 0.030), and gender (p = 0.046). In LUSC, RRM2 was associated with age (p = 0.008), pathologic stage (p = 0.006), and N stage (p = 0.001). RRM1 showed no significant associations with stage-related parameters in either subtype. Correlation analyses revealed modest associations between RRM1 and multiple oncogenic drivers, whereas RRM2 showed stronger subtype-specific correlations, particularly with KRAS/BRAF in LUAD and CDKN2A/SOX2 in LUSC. Kaplan-Meier analysis demonstrated that high expression of both RRM1 and RRM2 was associated with poorer overall survival in LUAD, but not in LUSC. However, neither marker remained significant after adjustment for clinicopathological variables in multivariate analysis. CONCLUSION: RRM2 is associated with tumor progression in both NSCLC subtypes, while the prognostic associations of RRM1 and RRM2 are confined to LUAD. Although neither marker demonstrated independent prognostic significance in multivariate analysis, the findings support subtype-dependent roles of RNR components and highlight the potential biological and therapeutic relevance of nucleotide metabolism pathways in LUAD.

Carcinoma, Non-Small-Cell Lung↗

PubMed2001

[Neurogenic appendicopathy: a frequent, almost unknown disease picture. Evaluation of 816 appendices and review of the literature].

BACKGROUND: Neurogenic appendicopathy (NA) represents an almost unknown pathology which clinically cannot be differentiated from acute appendicitis. The diagnosis can only be established histologically. Nerve proliferation and an increased number of endocrine cells are typical for NA. This study characterizes the epidemiology, histology, clinical appearance and therapy of NA. We evaluated the incidence of NA in macroscopically normal specimens from patients presenting the symptoms of acute appendicitis and in incidental appendectomies. PATIENTS AND METHODS: 816 routine appendix specimens were examined at the Institute of Pathology, University of Basel, for the presence of NA. We analyzed the indication for appendectomy, the histological form and the age and sex of the patients. RESULTS: 140 appendices (17.1%) showed the histological criteria for NA. 25% of incidental appendectomies were positive for NA, as opposed to 53% of the macroscopically normal specimens of patients presenting the symptoms of acute appendicitis (P < 0.0001). NA is more frequent in men than in women (19.5% versus 14.5%, P = 0.057). Out of the total of 140 NA, 105 (12.9%) were classified as central, 12 (1.5%) as intramucosal and 5 (0.6%) as submucosal forms of NA. 18 times (2.2%) the histologic subtype of NA was not specified. CONCLUSIONS: This study establishes that NA is a frequent, often asymptomatic pathology. In more than half of the macroscopically normal specimens of patients presenting symptoms of acute appendicitis NA can be diagnosed, significantly more than in incidental appendectomies. Therefore it is imperative to remove and analyze a macroscopically normal appendix in a patient presenting symptoms of acute appendicitis if no other intraabdominal pathology can be found.

Acute Disease↗

PubMed2005

Pathology parameters and adjuvant tamoxifen response in a randomised premenopausal breast cancer trial.

BACKGROUND: Subgroups of breast cancer that have an impaired response to endocrine treatment, despite hormone receptor positivity, are still poorly defined. Breast cancer can be subdivided according to standard pathological parameters including histological type, grade, and assessment of proliferation. These parameters are the net result of combinations of genetic alterations effecting tumour behaviour and could potentially reflect subtypes that respond differently to endocrine treatment. AIMS: To investigate the usefulness of these parameters as predictors of the response to tamoxifen in premenopausal women with breast cancer. MATERIALS/METHODS: Clinically established pathological parameters were assessed and related to the tamoxifen response in 500 available tumour specimens from 564 premenopausal patients with breast cancer randomised to either two years of tamoxifen or no treatment with 14 years of follow up. Proliferation was further evaluated by immunohistochemical Ki-67 expression. RESULTS: Oestrogen receptor positive ductal carcinomas responded as expected to tamoxifen, whereas the difference in recurrence free survival between control and tamoxifen treated patients was less apparent in the relatively few lobular carcinomas. For histological grade, there was no obvious difference in treatment response between the groups. The relation between proliferation and tamoxifen response seemed to be more complex, with a clear response in tumours with high and low proliferation, whereas tumours with intermediate proliferation defined by Ki-67 responded more poorly. CONCLUSIONS: Clinically established pathology parameters seem to mirror the endocrine treatment response and could potentially be valuable in future treatment decisions for patients with breast cancer.

Adult↗

PubMed1997

The spectrum of multiple myeloma: diagnostic and biological implications.

Myeloma is a common and well-studied hematopoietic neoplasm with an impressive spectrum of clinical, laboratory, and histological findings. To enhance our understanding of the diversity of myeloma, including its earliest forms, the clinical and pathological findings in 145 cases of myeloma were documented and analyzed. Our analysis indicated that myeloma has at least two distinct subtypes: one presenting with bone lesions and a nodular growth pattern and the other presenting with anemia and an infiltrative growth pattern. The relationship of these two forms to plasma cell biology is not clear, although both types appear to arise in the marrow. The criteria used in this study identified 85% of cases overall, with a range of 70% to 100%, depending on clinical presentation. Immunoperoxidase studies are required to establish the diagnosis in patients with early marrow involvement. Myeloma in younger patients appears to be clinically and pathologically similar to myeloma in older patients. Factors such as dysplasia, immunoglobulin type, or leukemic phase were evenly distributed among clinical presentations and did not apparently identify clinicopathological subtypes of myeloma.

Adult↗

PubMed2002

Pathologist's approach to diffuse lung disease.

The pathologic diagnosis of diffuse lung disease is based on the recognition of specific patterns closely correlated with the clinical history and the radiologic findings. The current pathologic classification of the idiopathic interstitial pneumonias is in flux, with the new creation of cellular and fibrotic subtypes of nonspecific interstitial pneumonia and further refinements in the criteria for usual interstitial pneumonia, desquamative interstitial pneumonia, and respiratory bronchiolitis-associated lung disease. The radiologist plays a pivotal role in the diagnosis of these conditions by using high-resolution computed tomography. The radiologist also provides an important service by guiding the clinician or surgeon, based on the site and extent of disease, in obtaining a sample that will provide the pathologist with appropriate diagnostic material. This article reviews the current pathologic criteria for the classification of idiopathic interstitial pneumonias, smoking-related disorders, hypersensitivity pneumonitis, as well as the lymphoproliferative disorder lymphocytic interstitial pneumonitis, with a focus on differential diagnoses.

Diagnosis, Differential↗

PubMedDate not supplied

[Positive and negative symptoms in schizophrenia: standards of change during acute exacerbation].

INTRODUCTION AND OBJECTIVES: The temporal stability of the positive and negative symptoms in schizophrenia deserves a special interest due to its consequences in the outcome and the treatment of the disease. This study determines the temporal stability of positive/negative subtypes in schizophrenia during the acute phase. MATERIAL AND METHODS: This is a clinical, observational and prospective study of a dynamic cohort of patients with acute exacerbation of schizophrenia defined by DSM III-R criteria. Patients with severe and unstable organic pathology, substance dependence, mental organic disorder, mental retardation, depression, or medicamentous parkinsonism were excluded. Clinical assessment was performed with the PANSS scale. Schizophrenic subtypes were established according to inclusive and restrictive criteria of PANSS. All patients were treated with new antipsycotics and biperiden if necessary. RESULTS: 51 patients were assessed for 8 weeks. In the baseline, the negative subtype (63.3% and 52.5% by inclusive and restrictive system respectively) and paranoid form (45.1%) were predominant. Three types of analysis were performed to determine the temporal stability: 1. Concordance (Kappa index). The concordance of the inclusive and restrictive System, regarding to the baseline assessment, indicated that both criteria had a low temporal stability. 2. Mc Nemar Ji Square. This test showed that these changes were bi-directional except for the first visit, which was significant through the restrictive system (higher change from the negative to other subtypes). 3. Transition analysis among groups by First Order Morkov Chains analysis indicated that this change was stationary (the change was the same in all phases). CONCLUSIONS: 1o The variable "time" has to be considered for the definition of subtypes in schizophrenia. 2o The restrictive system is more specific. It allows to identify a subgroup of patients with "Negative" schizophrenia with a high specificity and validity in clinical and epidemiological studies. 3o The use of the baseline visit as a reference (gold standard) is recommended because it exits a higher concordance among criteria and a more florid psychopathology.

Acute Disease↗