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PubMed2002

Lymphocyte predominant Hodgkin's disease.

Lymphocyte predominant Hodgkin's disease (LPHD) is a rare type of B-cell lymphoma with unique pathologic and clinical features that distinguish it from other types of Hodgkin's disease. Patients with LPHD tend to be younger males who present with indolent and asymptomatic lymphadenopathy limited to peripheral lymph nodes. The immunophenotype of the malignant lymphocytic and/or histiocytic cells (CD20+, CD15-, CD30-) forms the basis of the pathologic distinction from the subtypes of classical Hodgkin's disease. Despite an excellent response to aggressive upfront combined-modality treatment, patients with LPHD tend to relapse continuously over decades. The benign nature of these relapses and the incidence of late treatment-related toxicity have raised questions about the need for an aggressive upfront approach. Recent insights into the molecular pathogenesis of LPHD and the development of novel targeted therapies promise to improve future treatment.

Age Factors↗
PubMed2001

Asymptomatic Internal Carotid Artery Origin Stenosis.

Proper therapy for patients with internal carotid artery stenosis requires a precise pathophysiologic diagnosis that includes characterization and localization of ischemic disease of the brain and knowledge of the arterial disease and the collateral cerebral circulation. Noninvasive techniques such as duplex ultrasound and transcranial Doppler, magnetic resonance angiography, and CT angiography allow precise determination of the stroke subtype and parent arterial pathology. Antiplatelet agents prevent the formation of thrombus on carotid artery atherosclerotic plaque. 3-Hydroxy-3-methyglutaryl coenzyme A reductase inhibitors may help stabilize carotid plaques by altering the plaque morphology and reducing inflammation. Carotid endarterectomy, which is the only procedure proven to be beneficial for patients with asymptomatic disease, should be considered primary intervention. Until ongoing trials for interventional procedures are completed, carotid artery angioplasty and stenting should be considered only in patients with contraindications to carotid endarterectomy. It can be argued that an ideal clinical trial in a high-risk population has not yet been completed. This factor has become even more important with the development of stenting procedures. We have long advocated a trial of only treating patients with hemodynamically significant stenotic lesions (70% to 99%).

Journal Article↗
PubMed1994

Novel functions for subtypes of metabotropic glutamate receptors.

Metabotropic or "G-protein coupled" glutamate receptors (mGluRs) were discovered and established as a new type of excitatory amino acid receptor by their unique coupling mechanism (phosphoinositide hydrolysis) and pharmacological characteristics. Recently, the cloning of mGluRs and the availability of selective pharmacological agents has greatly increased knowledge of these receptors. It is now recognized that mGluRs are a highly heterogenous family of glutamate receptors with novel molecular structure that are linked to multiple second messenger pathways. Members of this family have unique pharmacological properties and function to modulate the presynaptic release of glutamate and the post-synaptic sensitivity of the cell to glutamate excitation. New information on mGluRs is elucidating the functions of mGluR subtypes in normal and pathological aspects of neuronal transmission. Basic knowledge of the role of specific mGluRs in CNS function and pathologies will further expand in the near future. This knowledge is providing the framework for the discovery of novel pharmacological approaches to modulate excitatory amino acid neuronal transmission.

Animals↗
PubMed2004

Rejection following donor or recipient preoperative treatment with FTY720 in rat small bowel transplantation.

BACKGROUND: Severe rejection of small bowel transplantation (SBTx) has been ascribed to abundant lymphoid tissues in the small intestine without well-established evidence. However, the role of donor lymphocytes in rejection is still unclear. The novel immunosuppressant, FTY720, is reported to transfer peripheral blood lymphocytes (PBLs) to lymphoid tissues such as mesenteric lymph nodes (MLNs) and Peyer patches (PP). In the present study, the number of donor lymphocytes in the graft was increased by FTY720, and the influence on rejection was studied in a rat model. Furthermore, the number of the PBL of recipient was decreased by FTY720 before SBTx and the effect on rejection was examined. MATERIALS AND METHODS: Orthotopic total SBTx was performed in Brown-Norway and Lewis rats. In the donor pretreatment study, FTY720 was administrated to donor rats 24 h prior to harvesting to increase the number of graft lymphocytes (FTY donor-pretreated group). In contrast, MLNs were surgically removed from the grafts to decrease the number of graft lymphocytes (MLN-resected group). In the recipient pretreatment study, FTY720 was administrated to recipient rats 24 h before SBTx to decrease recipient PBL (FTY group). In contrast, a subclinical dose of cyclosporine A (CsA) was administrated after SBTx (CsA group). Rats were administrated preoperative FTY720 combined with post-SBTx CsA (FTY+CsA group). Graft survival, pathology, lymphocyte count, and subtype were examined. RESULTS: In the donor pretreatment study, pretreatment with FTY720 did not enhance graft rejection. MLN resection did not prolong graft survival. In the recipient pretreatment study, FTY720 caused a significant reduction in the number of infiltrating lymphocytes in the graft, as well as the percentage of recipient CD4+ and CD25+ cells within the graft. FTY720 and CsA synergistically prolonged graft survival. CONCLUSION: SBTx rejection correlated with the number of recipient PBL, and not with the number of donor lymphocytes transplanted together with the graft. The pretreatment of the recipient with FTY720 was effective in the case of combined use of the low-dose postoperative CsA.

Adjuvants, Immunologic↗
PubMed2004

Subtyping female adolescent psychiatric inpatients with features of eating disorders along dietary restraint and negative affect dimensions.

Cluster-analytic studies of eating disorders in adult patients have yielded two subtypes (pure dietary and mixed dietary-negative affect). This study aimed to replicate the subtyping in female adolescent psychiatric inpatients with features of eating disorders. Cluster analyses of 137 patients with eating-disordered features revealed a dietary-negative affect subtype (43%) and a pure dietary subtype (57%). The dietary-negative affect subtype was characterized by greater likelihood of binge eating, greater eating-related psychopathology, and greater body image dissatisfaction. The two subtypes did not differ significantly in scores reflective of clinical syndromes (other than the significantly higher depressive affect in the negative affect subtype), but the dietary-negative affect subtype was characterized by greater personality disturbance and higher reported concerns in clinical areas, including suicidality and childhood abuse. The cluster analysis produced different results from an alternative approach to subtyping by vomiting. These findings provide further support for the reliability and validity of this subtyping scheme for eating pathology. Clinically, the findings suggest that the combination of dieting and negative affect signals a more disturbed variant of eating-disorder related psychopathology in female adolescent psychiatric inpatients.

Adolescent↗
PubMed2003

The core-binding factor leukemias: lessons learned from murine models.

The recent development of murine models of core-binding factor leukemias has provided important insights into the underlying molecular pathology of this common subtype of acute myeloid leukemia. Evidence from these models supports the idea that acute myeloid leukemia 1/core-binding factor beta-subunit (AML1/CBFbeta) has a critical role in the control of the self-renewal capacity of hematopoietic stem cells and their progeny. Moreover, the accumulated data demonstrate that the expression of translocation-encoded AML1 or CBFbeta fusion proteins are insufficient by themselves to induce a full leukemic phenotype. The models that have been developed should prove to be of value for defining the range of mutations that can cooperate with AML1/CBFbeta fusion proteins, and for assessing novel therapies targeted toward the pathways that are altered by the expression of these fusion proteins.

Animals↗
PubMed1996

Fungal sinusitis: an update.

OBJECTIVE: To review the classification of fungal sinusitis as well as discuss current approaches to diagnosis and management. DATA SOURCES: A MEDLINE literature search was performed using the index terms sinus infection, fungal, diagnosis, radiology, microbiology, and treatment. The search was restricted to the English language and human subjects. With one exception the references were restricted to the last 10 years. Clinical data from studies performed at our institution were also included. RESULTS: Fungal sinusitis can be divided into four primary categories: (1) acute/fulminant (invasive), (2) chronic/indolent (invasive), (3) fungus ball, and (4) allergic fungal sinusitis. Each subtype has unique immunologic, pathologic, and clinical features. Allergic fungal sinusitis is the most recently described and most common form. The treatment and prognosis of fungal sinusitis varies significantly among the four different categories. CONCLUSION: Recent advances in endoscopy and computed tomography have enhanced the understanding of fungal sinusitis; however, they remain diseases surrounded by controversy. New insights into the etiology and pathogenesis of these diseases along with advances in diagnosis and treatment will lead to improved medical therapy.

Humans↗
PubMed2002

Acute myeloid leukemia associated with nephrotic syndrome: case report and literature review.

The hematological malignancies associated with nephrotic syndrome are mainly Hodgkin's and non-Hodgkin's lymphomas and chronic lymphocytic leukemia. Acute myelogenous leukemia (AML) has rarely been described in association with the nephrotic syndrome. The clinical course of a 44-year-old patient with AML who presented with nephrotic syndrome is described and the clinicopathologic features of the other cases reported in the world literature are reviewed. We could not find a consistent pattern regarding the subtype of leukemia, renal pathology, and temporal relationship between the nephrotic syndrome and the leukemia or the response to treatment. The present case was unique in that the clinical course of the renal disorder correlated with the course of the leukemia responding to treatment with anti-leukemic agents. We conclude that nephrotic syndrome can also be associated with AML. In some cases there is a direct causal effect of the leukemic process on the renal pathology while in others it is exerted indirectly via other complications of the malignancy or the treatment.

Adult↗
PubMed1994

The pathology of autoimmune thyroid disease: a review.

Lymphocytic infiltration of the thyroid gland is the pathologic hallmark of autoimmune thyroid disease. Lymphoid cells are seen in the stroma of glands affected by Graves' disease. However, large lymphoid infiltrates are characteristic of that spectrum of diseases conveniently termed chronic lymphocytic thyroiditis. In this review, the pathology of the various subtypes of chronic thyroiditis is enumerated, including recently defined lesions, i.e., painless thyroiditis, thyroiditis associated with interleukin chemotherapy, and peritumor thyroiditis are reviewed. The unifying morphologic characteristics seen in these conditions are discussed.

Chronic Disease↗
PubMed2004

Use of the WHO lymphoma classification in a population-based epidemiological study.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) is pathologically diverse. Epidemiological investigations into its increasing incidence and aetiology require accurate subtype classification. PATIENTS AND METHODS: Available pathology reports of 717 cases aged from 20 to 74 years in an Australian, population-based epidemiological study of NHL were reviewed by one anatomical pathologist to assign a World Health Organization (WHO) classification category. High or low confidence was assigned to the diagnosis of NHL, cell phenotype and WHO category and reasons given for low confidence. RESULTS: The most informative biopsy reports were from open tissue biopsy (79% of cases), tissue core biopsy (8%), cytology (4%) and bone marrow (9%); 8% of cases had inadequate biopsies for diagnostic purposes. Immunohistochemistry or flow cytometry reports were available for 96% of cases, gene rearrangement studies for 6% and cytogenetics for 3%. The reviewer assigned high confidence to the diagnosis of NHL in 93% of cases and also the phenotype in 88%. While a WHO classification could be assigned in 91% of cases, confidence was high in only 57.5%; insufficient immunophenotyping was the commonest reason for low confidence. CONCLUSIONS: Expert pathology review of a population-based sample of NHL can provide a WHO classification category for most cases. A high level of confidence in the classification, however, would require review of diagnostic material and additional phenotyping.

Adult↗
PubMed2003

Multiple ipsilateral renal tumors discovered at planned nephron sparing surgery: importance of tumor histology and risk of metachronous recurrence.

PURPOSE: Unrecognized sporadic multifocality at planned nephron sparing surgery (NSS) presents a surgical dilemma. We report a single institution experience with patients presenting with multiple ipsilateral renal tumors, of which at least 1 was renal cell carcinoma (RCC). We determined the outcome for patients treated with NSS or radical nephrectomy (RN). MATERIALS AND METHODS: A total of 118 patients underwent surgery between 1970 and 2000 for sporadic multiple ipsilateral renal tumors, of which at least 1 was RCC. The patients were treated with RN (102) and NSS (16). Clinical features recorded included age at surgery, sex, history of smoking, a preexisting solitary kidney and symptomatic disease at presentation. Pathological features included histological subtype, nuclear grade, tumor stage (2003 TNM) and tumor size. Cancer specific survival was estimated using the Kaplan-Meier method. RESULTS: A greater proportion of patients treated with NSS had a solitary kidney compared with patients treated with RN (6 or 38% versus 0, p <0.001). Of the 102 patients treated with RN for multiple tumors 12 died of RCC at a median time to death of 3.3 years (range 3 months to 9.5 years). Estimated cancer specific survival at 5 years was 90.1%. There was metachronous contralateral recurrence in 5 patients a median of 8.1 years following RN (range 3 months to 14 years). Two of the 16 patients treated with NSS died of RCC 6 and 11 years following NSS, respectively, for a cancer specific survival rate of 100% at 5 years. Two patients had local renal recurrence 1.7 and 2.8 years following NSS, respectively, and a metachronous contralateral renal tumor was found in 1 patient 7 months following NSS. Of the 102 patients treated with RN 63 (62%) and 9 of the 16 (56%) treated with NSS had at least 1 clear cell RCC. In 23 of the 102 patients (23%) treated with RN only 1 tumor was RCC, while the remainder were benign, suggesting that these patients were potential candidates for NSS. CONCLUSIONS: Patients undergoing RN or NSS for multiple ipsilateral renal tumors, of which at least 1 is RCC, have favorable cancer specific survival. The metachronous contralateral recurrence rate for patients with sporadic multifocal lesions is approximately 5%. Planned NSS may not be abandoned if satellite lesions are benign.

Adult↗
PubMed2001

Microsatellite instability and the clinicopathological features of sporadic colorectal cancer.

BACKGROUND AND AIMS: In this study, we prospectively examined the clinical significance of the microsatellite instability (MSI) phenotype in sporadic colorectal cancer, and investigated methods for effective identification of these tumours in routine pathology practice. METHODS: DNA was extracted from 310 tumours collected from 302 consecutive individuals undergoing curative surgery for sporadic colorectal cancer. Microsatellite status was determined by polymerase chain reaction amplification using standard markers, while immunostaining was used to examine expression of MLH1, MSH2, and p53. RESULTS: Eleven per cent of tumours showed high level instability (MSI-H), 6.8% had low level instability (MSI-L), and the remainder were stable. MSI-H tumours were significantly more likely to be of high histopathological grade, have a mucinous phenotype, and to harbour increased numbers of intraepithelial lymphocytes. They were also more likely to be right sided, occur in women, and be associated with improved overall survival. In total, 25 (8%) tumours showed loss of staining for MLH1 and a further three tumours showed absence of staining for MSH2. The positive and negative predictive value of immunohistochemistry in the detection of MSI-H tumours was greater than 95%. CONCLUSIONS: We conclude that the MSI-H phenotype constitutes a pathologically and clinically distinct subtype of sporadic colorectal cancer. Immunohistochemical staining for MLH1 and MSH2 represents an inexpensive and accurate means of identifying such tumours.

Adult↗
PubMed2005

Ten year recurrence after first ever stroke in a Japanese community: the Hisayama study.

BACKGROUND: Very few population based cohort studies have focused on the long term recurrence of stroke. OBJECTIVE: To examine 10 year cumulative recurrence rates for stroke in a Japanese cohort according to pathological type and clinical subtype of brain infarction. METHODS: During a 32 year follow up of 1621 subjects >/=40 years of age, 410 developed first ever stroke. These were followed up prospectively for 10 years after stroke onset. RESULTS: During follow up, 108 (26%) experienced recurrent stroke. The cumulative recurrence rates were 35.3% at five years and 51.3% at 10 years. The 10 year recurrence rates of subarachnoid haemorrhage (SAH), brain haemorrhage, and brain infarction were 70.0%, 55.6%, and 49.7%, respectively; the difference between SAH and brain infarction was significant (p = 0.004). Most recurrent episodes after SAH or brain haemorrhage happened within a year after the index stroke, whereas recurrence of brain infarction increased consistently throughout the observation period. Cardioembolic stroke had a higher recurrence rate (75.2%) than lacunar infarction (46.8%) (p = 0.049). The 10 year risk of stroke recurrence increased with age after lacunar or atherothrombotic brain infarction, but not after the other types or subtypes. After atherothrombotic brain infarction, cardioembolic stroke, or SAH, the type and subtype of most recurrent strokes were the same as for the index stroke, but recurrence after lacunar infarction or brain haemorrhage showed divergent patterns. CONCLUSIONS: Japanese people have higher recurrence rates of stroke than other populations. Recurrence rate after a first brain infarct increases consistently through the next 10 years.

Adult↗
PubMed2006

Medical and surgical management of priapism.

Priapism is a pathological condition of penile erection that persists beyond, or is unrelated to, sexual stimulation. Pathologically and clinically, two subtypes are seen-the high flow (non-ischaemic) variety and the low flow (ischaemic) priapism. The low flow type is more dangerous, as these patients are susceptible to greater complications and the long term recovery of erectile function is dependent on prompt and urgent intervention. Many of the causes of priapism are medical, including pharmacological agents, and as such, priapism should be considered as a medical and surgical emergency.

Adult↗
PubMed1999

No loss of sst receptors gene expression in advanced stages of colorectal cancer.

As demonstrated by several studies, the pan-inhibitory peptide somatostatin (SS) is implicated in a large variety of physiological processes in the gastrointestinal tractus. SS inhibits hormonal and gastric acid secretions, and decreases gastric and intestinal motility, mesenteric blood flow and intestinal absorption. In vitro and in vivo studies showed also that the antiproliferative potency of SS analogs may be a target to improve the prognosis of colorectal cancer. Here we report the expression profile of the five SS receptor subtypes (hsst1-5) mRNAs in a large set of tumoral and normal colon. Using reverse transcription-PCR, we showed that hsst5, hsst1 and hsst2 mRNA subtypes were the most frequently expressed hsst mRNA subtypes in normal and pathological colon. Interestingly, we found that the frequency of hsst5 mRNA expression in the left colon was significantly higher in tumors than in normal samples: 81. 2% (13/16) and 36.4% (4/11) respectively (0.025>P>0.01, chi2 test with Yates' correction). We did not find any influence of Dukes' stage on hsst mRNAs expression. Of interest, no loss of hsst2 and hsst5 mRNA expression in advanced stages was noted. Some differences in the frequency of expression of hsst mRNAs according to the origin of the tissue (left or right colon) were evident. The expression of hsst5 and hsst2 mRNA in advanced colorectal carcinoma associated with the development of new SS analogs boost the relevance of colorectal cancer treatment by somatostatin analogs.

Aged↗
PubMed2002

Endothelin-1 and endothelin receptor antagonists as potential cardiovascular therapeutic agents.

Endothelin (ET)-1 is an endothelium-derived peptide with potent vasoconstrictor and proliferative properties. The ET system is activated in several cardiovascular disease states associated with functional and structural vascular changes, including hypertension and heart failure. The two ET receptor subtypes are known as ET(A)R and ET(B)R. The former is located mainly on vascular smooth muscle cells and is responsible for mediating vasoconstriction and proliferation. The latter is present predominantly on endothelial cells and mediates vasorelaxation as well as ET-1 clearance. Activation of smooth muscle ET(B)R causes vasoconstriction. Selective ET(A)R antagonists as well as nonselective ET(A)R-ET(B)R antagonists have been developed. Studies with animal models and early-phase clinical trials provided strong evidence that these agents are effective in the treatment of heart failure, essential hypertension, pulmonary hypertension, and atherosclerosis. However, the complexity of biologic effects mediated by two different receptor subtypes complicates therapy with selective versus nonselective ET receptor antagonists. In addition to subtype selectivity and potency, changes in receptor subtype distribution under different pathologic conditions and different patient populations will play a crucial role in the evaluation of these potentially therapeutic drugs.

Animals↗
PubMed2026

Feasibility, reliability, and clinical value of genomic assay on pre-therapeutic biopsy for endocrine receptor-positive HER2-negative early breast cancer.

Endocrine receptor-positive (ER+) and HER2-negative breast cancer (BC) represents approximately 80% of all BCs. Most patients are treated with upfront surgery; however, 15%-30% will develop late recurrences. Genomic assay indication is usually based on postoperative pathological data including histology subtype, tumor size, lymph node status, SBR grade, and Ki67. Performing genomic testing on core needle biopsy specimens prior to surgery may offer several advantages. In this manuscript, we assess the feasibility, reliability, utility, and potential benefits of such genomic analyses performed on core needle biopsies. Several factors may lead to proposing genomic assay analysis on biopsy: (1) optimization of the patient pathway by reducing time to therapeutic decision-making, (2) predicting response to neoadjuvant chemotherapy (NAC) or neoadjuvant endocrine therapy (NET), and (3) refining prognostic assessment to guide adjuvant chemotherapy decisions in patients for whom axillary surgery is not planned. Given the feasibility and reliability of genomic assay on core needle biopsies, it can be suggested that this practice may become more common in the near future. Knowledge of the evolutive risk determined by the result of genomic assay, as well as clinicopathological characteristics, allows more precise personalization of the therapeutic strategy, including the choice between upfront surgery and neoadjuvant therapy, the selection of systemic treatments, and decision-making in the absence of axillary staging.

breast cancer↗