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PubMed1990

The role of serotonin in cardiovascular diseases and their treatment.

Serotonin (5HT), discovered in the 1950s, has been the subject of renewed interest for several years, in particular due to the subdivision of 5HT receptors into various types. Concomitantly, several more or less selective agonists and antagonists for these various receptor subtypes have been developed. Although the physiologic relevance of 5HT remains largely unknown, its role in certain pathologic processes is widely accepted. Certain symptoms of the carcinoid syndrome, thromboembolic processes at the level of the microcirculation, and possibly also coronary spasm and peripheral vascular disease are likely to be associated, at least in part, with endogenous 5HT and serotonergic mechanisms. However, a primary and causative role for such mechanisms in essential hypertension seems unlikely. The blockade of peripheral 5HT2 receptors with drugs may offer advantages, in particular in those disorders where an interaction between predamaged blood vessels and platelets is involved. Such a therapeutic approach seems to be a more generally applicable principle than the lowering of blood pressure as such, which appears not to be a general phenomenon provoked by 5HT2-receptor blockade.

Animals↗

PubMed2001

Extrapleural pneumonectomy for diffuse malignant pleural mesothelioma. A treatment option in selected cases?

OBJECTIVE: There is no standard treatment for diffuse malignant pleural mesothelioma. Sporadic extrapleural pneumonectomy for the disease in off-protocol set has been performed when the disease was judged as being confined to a hemithorax. SUBJECT: To evaluate the role of extrapleural pneumonectomy in the treatment for the disease, cases that underwent surgery in a single institution are reported with descriptions of the stages based on the system from the International Mesothelioma Interest Group. METHODS: Patients with diffuse malignant pleural mesothelioma treated with extrapleural pneumonectomy from 1989 to 1995 at the National Cancer Center Hospital East were reviewed. RESULTS: Five patients underwent extrapleural pneumonectomy. All were male. Their ages ranged from 48 to 68 years. The disease was right-sided in two and left-sided in three. The histologic subtype was epithelial in three, and mixed epithelial and sarcomatous in the other two. Post-surgical pathologic stage was Ib (T1bN0M0) in three, III (T3N1M0) in one, and IV (T4N2M0) in one. There was no treatment-related death. Two cases with epithelial histology were alive with local recurrence on the chest wall at 75 months and at 51 months after surgery, respectively. A case with mixed epithelial and sarcomatous histology died of an esophageal cancer at 25 months after surgery. The two other cases died of the progressed disease at ten months and at four months after surgery, respectively. CONCLUSION: Extrapleural pneumonectomy for diffuse malignant pleural mesothelioma was concluded to be a treatment option in stage Ib cases with epithelial histology. To evaluate precisely the efficacy of surgery for the disease, a randomized control trial must be organized multi-institutionally.

Aged↗

PubMed2001

Remitting seronegative symmetrical synovitis with pitting oedema in a patient with myelodysplastic syndrome and relapsing polychondritis.

Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) may be the inaugural manifestation of different rheumatic diseases of the elderly, malignancies and myelodysplastic syndromes (MDS). Relapsing polychondritis (RP) is a rare systemic disorder characterised by an inflammatory process involving predominantly cartilaginous structures, the cardiovascular system and organs of special sense. We report on a 72-year-old man with RS3PE and MDS, refractory anaemia subtype, diagnosed at the same time as RS3PE. Several months later the patient presented a clinical and pathological picture compatible with RP. Although the association between RP and MDS is well known, no previous cases of RS3PE preceding RP have been reported. This case confirms that RS3PE may herald many diseases, among others autoimmune disorders such as RP.

Aged↗

PubMed2005

Rapid isolation of highly enriched and quiescent microglia from adult rat hippocampus: immunophenotypic and functional characteristics.

Isolation of microglia from CNS tissue provides a powerful tool to study basic microglia biology and examine the effects of in vivo treatments on microglia immunophenotype and function. Previous microglia isolation methodologies utilized whole brain. However, microglia immunophenotype varies across CNS anatomical loci, thus isolation of microglia from whole brain may obscure regional brain variations in microglia immunophenotype and function. In addition, it is unknown to what extent microglia isolation procedures alter the in situ immunophenotype and function of microglia. The present report details a procedure for the rapid isolation of microglia from discrete CNS anatomical loci and addresses the issue of whether the in situ microglia immunophenotype is significantly altered by the isolation procedure. The present microglia isolation method yielded highly enriched hippocampal microglia, which were devoid of other CNS macrophage subtypes and exhibited attributes reflecting a quiescent phenotype characteristic of microglia observed in situ under non-pathological conditions. Further, isolated microglia exhibited functional responsiveness to immunogenic stimuli ex vivo. The immunophenotypic and functional attributes of isolated microglia suggest that the isolation procedure preserves the in vivo phenotype of microglia, thus providing an experimental method with minimal procedural confounds for examining in vivo treatments on microglia ex vivo.

Animals↗

PubMedDate not supplied

What is the nature of the role of the serotonergic nervous system in learning and memory: prospects for development of an effective treatment strategy for senile dementia.

The serotonergic nervous system has long been suspected of playing an important role in the processes underlying learning and memory. However, owing frequently to inconsistent and divergent results, its precise role is difficult to define. Recently, there has been a renewed interest in this neurotransmitter's role in the processes underlying learning and memory. This has, in part, been due to the observations that this system appears to undergo significant deterioration as a result of the pathology associated with certain age-related cognitive disorders as well as the discovery of multiple receptor subtypes. Reviewed here are the results of a number of studies designed to gain further insight into the role the serotonergic nervous system plays in learning and memory. A variety of methods are used to manipulate this system, and the effects of these manipulations on performance in a variety of behavioral tasks are summarized. Consistent with past observations, it is difficult to incorporate the results of the present series of studies into a single unified theory of serotonin's role in learning and memory. However, it is clear that not all of the inconsistencies can be attributed to differences in the methods used to manipulate the system or in the types of tasks used to assess learning and memory. Some of the inconsistencies clearly belie a selective role of this neurotransmitter in the processes underlying learning and memory and further underscore the complex nature of this system's role in the processing of information by the brain.

Dementia↗

PubMed2002

Epilepsy surgery in children with focal cortical dysplasia (FCD): results of long-term seizure outcome.

The purpose of this study was to assess the effect of epilepsy surgery on seizure outcome in children and adolescents under 18 years with intractable epilepsy due to focal cortical dysplasia. We analysed clinical data, such as age at seizure onset, epilepsy course, localisation of focus from presurgical evaluation, MRI, tissue pathology and seizure outcome in 68 patients 6 months to 9 years after epilepsy surgery. Seizure outcome was classified according to the Engel classification. Mean age at seizure onset was 7 months, ranging from the first days of life to 7 years. All patients had medically intractable epilepsy. Localisation of the lesion was predominantly extratemporal: posterior (uni- or multilobar) 43 %, frontal without central region 26 %, multilobar involving central area 19 % and temporal in 12 %. MRI signs typically seen in cortical dysplasia (FCD) such as localised blurring of gray-white matter junction was found in 68 %, dysgyria in 62 %, thickening of the cortical ribbon in 46 % and T2 signal elongation of the subcortical white matter in 40 % of the patients' MRI. Age at surgery ranged from 5 months to 16 years; 14 patients were under 2 years when operated on. In 34 patients (6 patients under 3 years) subdural grid electrode evaluation was performed prior to surgery. Pathology revealed focal cortical dysplasia without balloon cells (type I) in 60 %, FCD of the balloon cell subtype (type II) in 40 % of the specimens. Postoperative complications were subdural hygroma in 5 and an increased motor deficit in 2 patients. Up to two years after epilepsy surgery 50 % of the children were seizure free (Engel class I), 10 % Engel class II, 33 % Engel class III and 7 % unchanged (Engel class IV). Long-term seizure outcome (> 3 years post surgery) in 32 patients showed similar results (class I 50 %, class II 19 %, class III 28 %, class IV 3 %). Complete resection of the dysplastic lesion was significantly correlated with favorable seizure outcome, whereas seizure outcome was not significantly different in patients with mild (type I) or balloon cell (type II) FCD. Children operated after 6 years of age had no better outcome than children operated in infancy or at preschool age. Epilepsy surgery resulted in good (class I and II) seizure control in 60 % of children with intractable epilepsy due to focal cortical dysplasia.

Adolescent↗

PubMed2006

Precursor B lymphoblastic lymphoma of the orbit in a child: an unusual presentation of a non-Hodgkin lymphoma.

OBJECTIVE: The majority of ocular adnexal lymphomas are marginal zone lymphomas, which occur rarely in children. This case report describes a 6 years old child with a precursor B lymphoblastic lymphoma presenting in the ocular adnexa. The combination of multi-agent chemotherapy with adjuvant radiotherapy seems to be necessary in order to achieve a complete remission of this subtype of lymphoma's in ocular adnexa. DESIGN: Retrospective case study. METHOD: A review of the clinical, pathological, radiological findings and follow-up in a patient from the files available at our center, which were reviewed between the years 1974 and 2004.

Child↗

PubMed1994

The role of prognostic factors in treatment selection for early-stage Hodgkin's disease.

PURPOSE: To identify poor prognostic factors in early-stage Hodgkin's disease that predict a high rate of relapse after radiotherapy alone. MATERIALS AND METHODS: A total of 153 patients with stages I and II supradiaphragmatic Hodgkin's disease, treated between 1964 and 1986 with either radiotherapy alone (120 patients) or combined modality therapy (33 patients), were studied retrospectively to determine factors affecting freedom from relapse and absolute survival. Median follow-up was 13 years. Clinical factors were assessed by the stepwise use of a stratified log-rank test and included maximum tumor dimension in any site (< or = 6 cm or > 6 cm), age (< or = 40 or > 40), presence or absence of B symptoms, pathologic and clinical stages (I or II), number of sites involved (< or = 4 or > 4), gender, histologic subtype, and large mediastinal mass (none, small [< or = 6 cm], large [> 6 cm]). RESULTS: The only factors independently predicting a high rate of relapse were tumor dimension (> 6 cm) and number of sites (> 4 sites). At 10 years, in patients with and without the two poor prognostic factors treated with radiotherapy alone, the freedom from relapse rates were 53% and 84% (p < .0001) and the absolute survival rates were 72% and 85% (p = .004), respectively. Combined modality therapy significantly improved freedom from relapse, but not absolute survival, in patients with one or both poor prognostic factors. CONCLUSIONS: Two poor prognostic factors were identified that were highly significant in predicting a high risk of relapse after radiotherapy alone. The addition of three cycles of chemotherapy to standard radiotherapy significantly reduced the relapse rate in high-risk patients.

Combined Modality Therapy↗

PubMed2003

Disease-modifying antirheumatic drug therapy for spondyloarthropathies: advances in treatment.

The inflammatory arthritides included in the category of spondyloarthropathy (ankylosing spondylitis, psoriatic arthritis, reactive arthritis, undifferentiated spondyloarthropathy, and arthritis associated with inflammatory bowel disease) may cause significant, progressive morbidity. Therapy with nonsteroidal antiinflammatory drugs and traditionally used disease-modifying antirheumatic drugs, such as methotrexate, often fails in patients with more severe peripheral arthropathy and axial involvement, and alternative treatment options have been limited. With increased understanding of the pathologic processes involved in these disorders, new therapeutics have arisen and are being investigated in the various subtypes of spondyloarthropathy. This article reviews recent progress in disease-modifying therapy for spondyloarthropathy, including new biologic response modifiers, such as the tumor necrosis factor-alpha inhibitors etanercept and infliximab.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1992

Cytokine and natural killing regulation of growth of a hairy cell leukemia-like cell line: the role of interferon-alpha and interleukin-2.

Hairy cell leukemia (HCL) is a lymphoproliferative disorder of B-lymphocytes, with pathological manifestations usually including splenomegaly and pancytopenia. Naturally occurring and recombinant interferons (IFNs), specifically of the alpha subtype, have shown a significant anti-tumor effect in HCL patients, with improvement of hematologic parameters within the first few months of treatment. The mechanisms responsible for the beneficial action of IFN-alpha in HCL patients are unclear, but several hypotheses have been suggested. Recently, a continuous line of cells (Eskol) from a patient diagnosed with hairy cell leukemia was established and shown to have several properties of a leukemic hairy cell. In the present study, we investigated the direct effect of IFN-alpha and interleukin (IL-2) on the Eskol cell line, and lymphokine regulation of natural killing (NK) activity against these cells. It was found that IFN-alpha has a direct antiproliferative effect on Eskol cells. Furthermore, Eskol cells were found to be completely resistant to NK-cell mediated cytotoxicity (CMC) but were somewhat sensitive to either IFN-alpha-primed NK or lymphokine-activated killer (LAK) cells-CMC. The resistance of Eskol cells to NK-CMC is due to a low binding ability to effector cells. Moreover, it was found that like IFN, IL-2 can protect Eskol cells from activated NK-CMC. Both cytokines reduced the ability of Eskol cells to induce NK-cytotoxic factor (NKCF) release from NK cells following conjugate formation between Eskol cells and effector cells. Moreover, cycloheximide treatment abolished the protective effect against NK-CMC induced by IFN-alpha or by IL-2. Therefore, it seems that the protective effect against NK-CMC induced by both cytokines is mediated via the same mechanism.

Cell Division↗

PubMed1997

Pathological variants of basal cell carcinoma.

Although the pathological features of basal cell carcinoma are well known, there is no generally agreed classification of the subtypes of this tumour. Certain histological subtypes are associated with indistinct clinical margins, inadequate primary excisions and frequent recurrences, and these must be recognized and reported by pathologists so that the most appropriate therapy is given. The current classification of subtypes of basal cell carcinoma is discussed and reference made to the rarer forms of this tumour.

Biopsy, Needle↗

PubMed1997

The Revised European-American Classification of Lymphoid Neoplasms (REAL): a new perspective for the classification of cutaneous lymphomas.

Differing classification schemes for malignant lymphomas have been used in Europe and the United States. Attempts to translate between the principle classifications have been unsuccessful and historically it has been difficult to arrive at an unified approach. In addition, many new lymphoma entities have been recognized in recent years that are not delineated in any of the existing classification schemes. To provide a unified international basis for clinical and investigative work in this field, in 1994 the International Lymphoma Study Group (ILSG) proposed a new classification termed Revised European-American Classification of Lymphoid Neoplasms (REAL). This review discusses the REAL classification, especially as it pertains to cutaneous lymphomas, and provides insight into the clinicopathologic features of lymphoproliferative disease involving the skin. The premise of the REAL classification is that a classification scheme should be based on the delineation of disease entities, utilizing pathologic, immunophenotypic, genetic, and clinical features. Therefore, if cutaneous involvement is an integral aspect of any lymphoma subtype, this clinical information is included in the definition of that neoplasm. We conclude that the principles of the REAL classification are applicable to cutaneous lymphomas, as well as lymphomas involving other anatomic sites.

Humans↗

PubMed2002

High incidence rates of stroke in Orebro, Sweden: Further support for regional incidence differences within Scandinavia.

BACKGROUND AND PURPOSE: As a basis for comparison of differences in stroke incidence in Scandinavian countries, a community-based stroke register was established in Orebro in the centre of Sweden. METHODS: All first-ever cases of stroke were registered during a 12-month period 1999-2000. The study population was 123,503. The WHO definition of stroke was used. Cases were searched inside as well as outside hospital. Multiple overlapping sources and 'hot pursuit' technique were used in the process of case ascertainment. RESULTS: 388 cases of first-ever stroke were found, corresponding to a crude incidence rate of 314 (95% CI, 283-348) per 100,000 per year, 337 (95% CI, 294-386) for females, and 289 (95% CI, 248-336) for males. Adjusted to the European population, the corresponding rates were 254 (95% CI, 227-284) per 100,000 per year, 273 (95% CI, 238-311) for females and 232 (95% CI, 206-261) for males. The overall 28-day case-fatality rate was 19% (95% CI, 15-23). The case-fatality rates for the different subtypes of stroke were as follows: brain infarction, 10%; intracerebral haemorrhage, 20%; subarachnoidal haemorrhage 45%, and undetermined pathological type 56%. CONCLUSIONS: The present study as well as other studies in northern and middle Scandinavia show significantly higher incidence rates than studies from other regions. The crude incidence rate, reflecting the age distribution of the population, is even higher, indicating a burden to the community that is rather increasing than decreasing.

Adult↗

PubMed2004

Continuous recording of blood pressure in cerebrovascular disease: when should it be done?

BACKGROUND AND OBJECTIVES: Ambulatory blood pressure (BP) monitoring has found some specific clinical indications in the treatment and control of hypertension (HT). As with other target organs exposed to vascular damage dependent on HT, ambulatory BP monitoring can be a useful tool in the prevention of cerebrovascular processes. METHOD: Review of published articles (Medline database) which have investigated the value of continuous recording of BP in cerebrovascular disease (CVD). RESULTS: Research on the BP patterns and its relationship with stroke has been carried out in subjects with no previous history of CVD (cohort studies and in patients with essential HT, differentiating between adults and elderly patients) and patients after a cerebral ischemic event. The study objectives are aimed at determining its prognostic value in the development of silent and symptomatic CVD, and its prognostic significance regarding functional recovery and the differences of the BP patterns according to the different stroke subtypes. CONCLUSIONS: BP monitoring is a useful technique with applications in the control and treatment of the pathological variations of BP in hypertensive patients, with and without a previous history of cerebral ischemia, and mainly in elderly patients, due to the deterioration of the cerebral circulation regulation mechanisms. Clinical research has confirmed the importance of factors related to the circadian rhythm of BP in the primary and secondary prevention of cerebrovascular processes.

Blood Pressure Monitoring, Ambulatory↗

PubMed1996

Morphologic patterns and molecular pathways of AIDS-related head and neck and other systemic lymphomas.

Head and neck manifestations of human immunodeficiency virus (HIV) infection include lymph nodal and extranodal localization of non-Hodgkin's lymphoma (NHL). A histopathologic characteristic common to head and neck NHLs and to all the other systemic lymphomas in HIV patients is the frequent occurrence of cases displaying pleomorphic features and some overlap between established histologic subtypes. This article highlights the difficulties in defining HIV-related NHLs correctly, and proposes a specific pathologic categorization of these disorders accounting for their pathogenic aspects as gathered from molecular data.

Acquired Immunodeficiency Syndrome↗

PubMed1987

Klinefelter's syndrome associated with mediastinal germ cell neoplasms.

Several case reports have suggested an association of primary mediastinal germ cell tumor (PMGCT) and Klinefelter's syndrome (KS). In an effort to confirm this association, 22 patients with mediastinal germ cell tumors had chromosome studies performed in a prospective fashion. Five patients (22%) had karyotypic or pathologic evidence of KS. All of the patients with KS had germ cell tumors of the nonseminomatous subtype and were relatively young (median age, 15 years). The literature confirms the findings of a young median age (18 years), nonseminomatous subtype, and mediastinal location of the germ cell neoplasm. We conclude that patients with KS are predisposed to the development of mediastinal nonseminomatous germ cell cancers.

Adolescent↗

PubMed2005

Functional proteins involved in regulation of intracellular Ca(2+) for drug development: desensitization of N-methyl-D-aspartate receptor channels.

N-Methyl-D-aspartate (NMDA) receptors are a principal subtype of excitatory ligand-gated ion channels with crucial roles in a variety of physiological and pathological processes in the mammalian central nervous system (CNS). In contrast to synaptic non-NMDA receptors that rapidly internalize, synaptic NMDA receptors have been shown to be rather static. However, recent accumulating evidence gives rise to the possibility that NMDA receptors may also undergo internalization. In our studies, repeated but not sustained stimulation by an agonist indeed induced desensitization of NMDA-receptor channels, which may be due to a decrease in the number of NMDA receptors expressed on cellular surfaces by internalization in a manner similar to the clathrin-induced endocytosis. Desensitization of NMDA-receptor channels provides a clue for the elucidation of fundamental mechanisms underlying dynamic regulation of the number of NMDA receptors at synapses, which is undoubtedly critical for the maintenance of both integrity and functionality in the CNS.

Adaptor Protein Complex 2↗

PubMed2003

Adenosine signalling pathways in the pituitary gland: one ligand, multiple receptors.

Adenosine receptors are widely distributed in most species and mediate a diverse range of physiological and pathological effects. Although adenosine receptors have been identified in the pituitary gland, the distribution of the individual subtypes (A(1), A(2A), A(2B), A(3)) has not been well defined. Furthermore, the effects of adenosine on pituitary trophic activity and function are not well established despite good evidence for growth- and immune-modulating properties of the nucleoside elsewhere. Recent advances have provided a more detailed description of adenosine receptor distribution and function in the anterior pituitary and this commentary reviews these observations and highlights some of the possible implications in relation to the control of the hypothalamic-pituitary-adrenal axis and the regulation of inflammation and pituitary cell growth.

Adenosine↗