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ID PMID Title PublicationDate abstract
15384843 [Immunologic peculiarities of uveitis concurrent with systemic pathologies]. 2004 Jul Immunologic examinations were performed in 111 patients with uveitis concurrent with a variety of systemic pathologies, including 85 males and 26 females, mean age--32.4 +/- 5.8. A higher IL-6 content in blood serum (BS) and in lachrymal fluid (LF) was detected in all patients. The IL-4 content was lower in uveitis associated with ankylosing spondylitis and with Reuter's disease, whereas, it was higher in juvenile rheumatoid arthritis. The systemic immunity changes were related with the hemostasis impairments in the phagocytic, humoral and cellular chains: an enhanced functional activity of phagocyte cells, a lower absolute quantity of T-lymphocytes, a higher count of B-cells, a reduced concentration of IgM and of circulating immune complexes (CIC), and a diminished general hemolytic activity of the complement in BS. A reduced concentration of the secretory fraction of IgA, IgG and IgM concurrent with higher concentrations of IgA, C3- and C4 complement components, CIC and of lysozyme activity in LF was detected in the local immunity system.
15301242 Comparison of the baseline disease activity of early oligo- and polyarthritis in sequentia 2004 Jul OBJECTIVE: Many early arthritis clinics (EACs) have been started in the last decade in order to detect and treat rheumatoid arthritis early. The present study evaluates whether the disease activity at admission of patients with early oligo- and polyarthritis changed during the period 1993--1998 in two EACs in the Netherlands. METHODS: Patients were selected who were diagnosed after one year as having rheumatoid arthritis (RA) or oligo- or polyarthritis (UPA), had a symptom duration of less than 2 years, and were referred from two Dutch EACs between 1993 and 1998. The data from the two clinics were combined and stratified by referral year. Differences in baseline disease characteristics as well as changes in radiological and functional scores after two years of follow-up between referral years were analysed by ANOVA using Bonferroni corrected p levels. RESULTS: A total of 405 patients (66% females; median age 57 yrs (18-93): 80% diagnosed as RA, the remainder as UPA) were included in the study. The year-groups did not differ significantly in demographic characteristics or in the duration of complaints (median 6 months). The number of patients with a diagnosis of RA declined over the years, as did the mean baseline erythrocyte sedimentation rate (ESR), in RA and UPA patients. The functional status (Health Assessment Questionnaire: HAQ) was enhanced in 1998 compared with the previous years (p < 0.001). Radiographic progression (Sharp/van der Heijde score) after the 2-year follow-up decreased (p < 0.001) in the later referral years compared to the referral group of 1994. Disease modifying anti-rheumnatic drugs (DMARDs) were started in an earlier stage and the prescription rate of sulfasalazine and methotrexate increased over the years, whereas the number of patients not treated with DMARDs declined. CONCLUSION: The pattern of patient referral changed over 6 years towards fewer patients who fulfilled the RA diagnosis and a lower ESR (among UPA as well as RA patients), whereas the number of swollen joints and the duration of complaints remained the same. The radiological progression declined over time, probably due to less inflammation at the first visit and the increased use of DMARDs.
14749997 A case of adult-onset Still's disease presenting with angioedema. 2004 Feb Adult-onset Still's disease (AOSD) is the adult form of Still's disease. In addition to classic symptoms, rarely urticaria may be seen. The author here presents a case of AOSD in which the patient presented with angioedema and urticaria.
12631160 Periodontitis, caries and salivary factors in Sjögren's syndrome patients compared to sex 2003 Apr The aims of this investigation were: (i) to study a group of dry mouth Sjögren's syndrome (SS) patients comprising individuals with pathological and non-pathological amounts of rest saliva and (ii) to compare these two categories of SS patients with a sex- and age-matched control group with respect to their periodontal and dental status. Thirty-three dry mouth patients and 33 sex- and age-matched patients, referred to the same private dental clinic in southern Norway, were examined for rest and stimulated saliva, as well as their dental and periodontal status. All patients were referred to the local hospital for blood and urine examinations. The dry mouth SS patients were all of the secondary type. Volumes of rest and stimulated saliva were significantly lower in the low saliva SS group compared with the high saliva SS group; the values for immunoglobulin G (IgG) and IgA were similarly lower for the low saliva group, but not for IgM which was significantly higher. The two SS subgroups and their controls were compared for the volume of rest and stimulated saliva, which showed a statistically significant lower volumes for the low saliva SS group compared with the control group. None of the subgroups and their controls differed concerning filled or missing teeth, but the total SS group revealed significantly higher number of missing teeth. The periodontal and dental status did not show any statistically significant differences except for a few scattered higher periodontal level losses of attachment in the SS subgroups. The blood and urine analyses showed statistically significant higher values for sedimentation rate, white blood cell count and haemoglobin in the SS low saliva group compared with the control group while anti-streptolysin was lower. In the high saliva SS group only sedimentation rate and white cell count were higher compared with the control. The conclusions is SS patients do not have an increased risk for developing periodontitis.
12565811 Quantitative analysis of lacrimal gland function, apoptotic figures, Fas and Fas ligand ex 2003 Feb The purpose of our study was to examine the correlation between the lacrimal gland function and apoptotic figure, Fas and Fas ligand (FasL) expression in the lacrimal gland. A total of 15 dry eye patients (nine Sjögren's syndrome and six non-Sjögren's syndrome-type dry eye) were recruited for the study. Lacrimal function was evaluated by Schirmer tests 1 and 2. Lacrimal gland biopsies were performed and sections were analyzed by immunohistochemistry using APO2.7, an antibody to Fas and FasL. Quantitative analysis of fluorescein staining was performed by a scanning laser microscopy. Schirmer test 2 results were lower in Sjögren's syndrome-type dry eye and were associated with positive staining of acinar cells with APO2.7 and of infiltrating lymphocytes with FasL. There was a good correlation between the results of Schirmer test 2 and APO2.7 and FasL staining. Lacrimal gland dysfunction is related to the apoptotic figure of acinar cells possibly induced by FasL on the infiltrating lymphocytes.
12027834 Myelopathy in primary Sjögren's syndrome: diagnostic and therapeutic aspects. 2002 Jun We report a patient with a myelopathy in primary Sjögren's syndrome, proven by salivary gland biopsy and specific antibodies. Under steroid medication, the patient had a remitting and relapsing clinical course. The severity of clinical symptoms correlated with a transient contrast uptake in spinal magnetic resonance imaging. Under a treatment with azathioprine and prednisone the patient has suffered no relapse within the last 20 months. Although this is only a case report, the combination of azathioprine and prednisone may be a valuable medication in chronic cases of Sjögren's syndrome with neurologic symptoms.
15618835 Overlap syndrome of autoimmune pancreatitis and cholangitis associated with secondary Sjö 2004 Nov In approximately 25% of patients with acute or chronic pancreatitis the cause remains unclear. Despite progress in understanding so-called idiopathic pancreatitis, more diagnostic criteria are needed. We report on a patient who presented with jaundice, but without pain or fever. Under the assumption of pancreatic cancer the patient underwent hemipancreatoduodenectomy. Histological examination showed chronic sclerosing inflammation of the pancreas and bile ducts without any signs of malignancy. Ten weeks later he developed bilateral parotid swelling and recurrent bouts of fever. Again liver enzymes were elevated and unsuccessfully treated with antibiotics for bacterial cholangitis. Further biopsies from submandibular gland, lymph nodes and liver again showed chronic sclerosing inflammation with lymphoplasmacytic infiltration. For sicca symptoms the diagnosis of a primary Sjogren's syndrome was proposed. However, with corticosteroid treatment the patient improved remarkably but after tapering he relapsed. On the basis of established criteria, we diagnosed autoimmune pancreatitis with (1) diffuse swelling of the pancreas, (2) irregularities of the pancreatic duct, (3) lymphoplasmacytic infiltration, (4) response to corticosteroids, (5) hypergammaglobulinaemia, and (6) disproportionately raised IgG4. In addition, the patient fulfilled the criteria for secondary Sjogren's syndrome. Autoimmune pancreatitis may present as an isolated or syndromic disease. It is an autoimmune disorder of unknown cause and should be included in the differential diagnosis of pancreatic disorders.
15314488 Apoptosis and estrogen deficiency in primary Sjögren syndrome. 2004 Sep PURPOSE OF REVIEW: Primary Sjögren syndrome is an autoimmune disorder characterized by lymphocytic infiltrates and destruction of the salivary and lacrimal glands, and systemic production of autoantibodies to the ribonucleoprotein particles SS-A/Ro and SS-B/La. The purpose of this review is to discuss recent advances in the pathogenesis of primary Sjögren syndrome. RECENT FINDINGS: Although several candidate autoantigens including alpha-fodrin have been reported in Sjögren syndrome, the pathogenic roles of the autoantigens in initiation and progression of SS are still unclear. It is possible that individual T cells activated by an appropriate self antigen can proliferate and form a restricted clone. Recent evidence suggests that the apoptotic pathway plays a central role in tolerizing T cells to tissue-specific self antigen, and may drive the autoimmune phenomenon. Cleavage of certain autoantigens during apoptosis may reveal immunocryptic epitopes that could potentially induce autoimmune response. The studies reviewed imply that Fas-mediated cytotoxicity and caspase-mediated alpha-fodrin proteolysis are involved in the progression of tissue destruction in Sjögren syndrome. Fas ligand (FasL), and its receptor Fas are essential in the homeostasis of the peripheral immune system. It can be considered that a defect in activation-induced cell death of effector T cells may result in the development of autoimmune exocrinopathy in Sjögren syndrome. SUMMARY: Although the mechanisms by which estrogen deficiency influences autoimmune lesions remain unclear, it is possible that antiestrogenic actions might be a potent factor in the formation of pathogenic autoantigens.
15005005 Sjögren's syndrome: a retrospective review of the cutaneous features of 93 patients by th 2004 Jan OBJECTIVE: Various cutaneous manifestations have been described (xerosis, eyelid dermatitis, angular cheilitis, cutaneous vasculitis and annular erythema) in Sjögren's syndrome (SS), but so far only three studies on large numbers of SS patients have been carried out. The frequency of cutaneous manifestations and their association with specific clinical or immunological parameters have never been studied. The aim of the Italian Group of Immunodermatology was to evaluate these associations in a large number of SS patients. METHODS: A retrospective review was performed on 93 patients with SS followed over a ten-year period (1990-2000) at 6 Italian dermatological centers. They were subdivided into two groups, 62 with primary SS and 31 with secondary SS, and the frequency of cutaneous manifestations and specific antibodies was determined and compared between them. RESULTS: We found significantly higher levels of xerosis (p = 0.009) (56.4% versus 25.8%) and angular cheilitis (p = 0.017) (38.7% versus 16.1%) in primary SS patients than in those with secondary SS. A significant association of xerosis with anti-SSA + SSB (p = 0.033) antibodies was also demonstrated. Eyelid dermatitis and pruritus were common but less specific cutaneous symptoms. Annular erythema was found more often in primary (6.45%) than in secondary (3.2%) SS and was associated with SSA + SSB antibodies in 75% of the cases. Cutaneous vasculitis was present in 30.6% of primary SS (manifesting as palpable purpura in 84%) and in 29.3% of secondary SS cases. CONCLUSION: Xerosis is the most frequent and characteristic cutaneous manifestation of primary SS. It is not linked to decreased sebaceous or sweat gland secretion, but more probably to a specific alteration of the protective function of the stratum corneum. Angular cheilitis is a common but less specific skin lesion in SS and is associated with xerosis and xerostomia.
12180736 A cross sectional study of the association between sex, smoking, and other lifestyle facto 2002 Aug OBJECTIVE: To describe the association between sex, smoking, physical activity, occupation, and previous digit fracture and hand osteoarthritis (OA). METHODS: Cross sectional study of 522 subjects from 101 Tasmanian families (348 women, 174 men). Hand OA was assessed by 2 observers using the OARSI atlas for joint space narrowing and osteophytes at distal interphalangeal (DIP) and carpometacarpal joints as well as a score for Heberden's nodes based on hand photography. A structured questionnaire collected information regarding physical activity, sport participation, occupation, and smoking history. RESULTS: Women had a higher prevalence of hand OA and the increase with age was significantly higher for women at all sites (all p < 0.05). Ever smoking was associated with less frequent (OR 0.59, 95% CI 0.38, 0.92) and less severe Heberden's nodes (beta -0.60, 95% CI -1.03, -0.17), but not radiological disease. Recall of occupation, physical activity, and sport participation between the ages of 20 and 40 years had no association with the prevalence or severity of hand OA, while self-reported digital fracture was significantly associated with more common (OR 2.42, 95% CI 1.22, 4.83) and severe DIP joint disease (beta +3.92, 95% CI +1.50, +6.36). No factors were associated with carpometacarpal disease. CONCLUSION: In this sample, women had a higher prevalence of hand OA at all sites as well as greater severity and a steeper age gradient (implying higher incidence rates). Smoking may decrease the risk of Heberden's nodes while having no effect on radiological hand OA, suggesting a differential effect possibly at the time of disease onset. With the exception of digital fracture, these data do not support a causal role for occupation or activity in earlier life with regard to hand OA.
11961175 Primary Sjögren's syndrome associated with inclusion body myositis. 2002 Apr OBJECTIVE: To describe three new patients with inclusion body myositis (IBM) associated with primary Sjögren's syndrome (pSS) and summarize the clinical and serological picture for all six patients reported so far. PATIENTS AND METHODS: Three out of 518 (0.6%) pSS patients followed in our department over a period of 15 yr (1985-2000) also presented IBM. The diagnosis was based on histological criteria. Previous reports described four more patients with IBM associated with pSS. Five out of six were females; the mean age of IBM onset was 53.3+/-14.0 yr and the disease duration 8.0+5.8 yr. RESULTS: Four out of six patients presented IBM several years after the onset of pSS. Four out of six patients presented extraglandular manifestations, such as arthralgias, vitamin B12 deficiency, interstitial kidney disease and biliary cirrhosis. The serological picture did not differ significantly from that observed in pSS alone. CONCLUSION: Although rare, IBM may be seen in patients with pSS and it affects predominantly women. The clinical and pathological pictures do not differ from those observed in idiopathic IBM. A common autoimmune pathway in these two diseases, but no definite conclusions can be drawn.
15088298 CD4+ T-lymphocytopenia--a frequent finding in anti-SSA antibody seropositive patients with 2004 Apr OBJECTIVE: Case reports have described an association between idiopathic CD4+ T-lymphocytopenia (ICL) and non-Hodgkin's malignant lymphoma (NHML), and both entities have an increased prevalence in patients with primary Sjögren's syndrome (SS). We investigated lymphocyte subset counts in patients with primary SS to determine if presence of different autoantibodies is associated with ICL and hence may represent an increased risk for development of NHML. METHODS: A total of 80 patients with primary SS according to the American-European Consensus Classification Criteria (AECC) and 37 non-AECC sicca patients were studied for presence of different autoantibodies, and lymphocyte subsets were investigated by flow cytometry. RESULTS: Absolute CD4+ T-lymphocyte counts were significantly lower among anti-SSA antibody seropositive SS patients compared to correlating seronegatives and non-AECC sicca patients (601/microl vs 956/microl and 1087/microl; p < 0.001 and p < 0.001, respectively). ICL was found in 16% of anti-SSA seropositive patients. CONCLUSION: ICL, a proposed risk factor for development of NHML, occurs frequently and presumably exclusively in patients with primary SS who are anti-SSA antibody seropositive. These findings support that this group comprises patients at risk for development of NHML.
12858457 Pure sensory neuropathy in primary Sjögren's syndrome. Longterm prospective followup and 2003 Jul OBJECTIVE: To study the clinical course, response to therapy, and longterm outcome of pure sensory neuropathy (PSN) in a series of patients with primary Sjögren's syndrome (SS) followed prospectively in our referral centers. METHODS: We studied 15 patients (13 women, 2 men) with primary SS and PSN. All patients fulfilled 4 or more of the European diagnostic criteria. RESULTS: At diagnosis of PSN, clinical manifestations included numbness and paresthesias (11 patients), trigeminal neuropathy (6 patients), and Adie's pupil syndrome (4 patients). In 7 patients, PSN was diagnosed prior to SS, in 5 the diagnoses were made simultaneously, and in the remaining 3 patients PSN was diagnosed after the appearance of SS symptomatology. The mean duration of the prospective PSN followup was 10 years (range 1-20). The progression of PSN was acute in 1 patient (producing severe dysfunction in less than 1 month), subacute in 3 patients, and in the remaining 11, the symptoms progressed slowly over the ensuing years to other extremities. Patients were treated with corticosteroids (n = 13), cyclophosphamide (n = 4), and intravenous immunoglobulins (n = 1), and 2 patients received no treatment. In spite of treatment, most patients showed an indolent and insidious longterm PSN course. CONCLUSION: We found 3 differentiated clinical courses of the PSN in patients with primary SS: subacute progression in less than 1 month (7%), late acceleration of PSN 2-4 years after an initial indolent onset (20%), and a very longterm insidious, chronic evolution (73%). Prospective analysis of the longterm course of PSN shows a chronic and insidious evolution in most patients with PSN and SS, with a poor response to treatment, although stabilization of symptomatology for long periods is often observed.
12050508 Prevalence of symptoms related to interstitial cystitis in women: a population based study 2002 Jul PURPOSE: Interstitial cystitis is a chronic inflammatory bladder disease. Despite intensive research its prevalence, etiology, diagnosis and appropriate treatment remain elusive. We estimated the prevalence of urinary symptoms related to interstitial cystitis in women in Finland. MATERIALS AND METHODS: We randomly selected 2,000 study participants 18 to 71 years old from the Finnish population register. The prevalence of urinary symptoms was evaluated using the validated O'Leary-Sant interstitial cystitis symptom and problem index questionnaire, which was mailed to subjects. Women with high (12 or greater) symptom and problem scores, including nocturia 2 or greater, pain 2 or greater, and excluding urinary infection and pregnancy, were considered most likely to have interstitial cystitis. RESULTS: The response rate after 2 mailings was 67.2% (1,343 respondents). After further exclusions 1,331 women (66.6%) comprised the final study group. Of these 1,331 respondents 11 (0.8%) reported severe symptoms and problems (12 or greater), including 6 (0.45%) who fulfilled the criteria for probable interstitial cystitis. CONCLUSIONS: The prevalence of urinary symptoms corresponding to probable interstitial cystitis is 450/100.000 (95% confidence interval 100 to 800), which is an order of magnitude higher than previously reported.
12707573 Genotypes and phenotypes: should genetic markers and clinical predictors drive initial tre 2003 May Using patients' genetic and phenotypic profiles to identify the best available drug therapy for individual cases remains a clinical aspiration. Considerable recent research has developed this theme in rheumatoid arthritis (RA). Seven reports have evaluated how the high-risk epitope and other genes influence RA susceptibility and severity. There is strong evidence that the shared epitope influences susceptibility, but inconclusive evidence concerning whether it effects severity. The interleukin-1 gene cluster and IL-4/IL-4 genes influence erosive disease, but their effects are mainly in late RA. A further ten studies examined links with erosive disease. Fewer reports evaluated phenotypes: six studies examined outcome predictions using rheumatoid factor and antikeratin/anticyclic citrullinated peptide antibodies and two looked at conventional clinical measures. Anticyclic citrullinated peptide antibodies are useful in establishing the diagnosis of RA, but rheumatoid factor potentially provides the most useful prognostic information. The value of genotyping RA patients in defining their clinical course and determining the most suitable treatment remains unproven.
12942703 Association between HLA-DR B1 and clinical features of adult onset Still's disease in Kore 2003 Jul OBJECTIVE: To determine whether HLA-DR alleles are associated with the development and clinical features of Adult Onset Still's Disease (AOSD) in Korea. METHODS: Forty-seven patients (41 women, 6 men, mean age at diagnosis 31.6 yr) meeting Yamaguchi's criteria for AOSD and 144 healthy controls were enrolled in this study. The patients with AOSD were subdivided into groups according to their chronicity: monocyclic systemic, polycyclic systemic, and chronic destructive type, and were furthermore classified as non-articular, oligoarticular or polyarticular types (having arthritis involving 5 or more joints) according to the extent of articular involvement. HLA-DRB1 genotypes were assessed by PCR-SSOP. RESULTS: Patients with AOSD had more frequent DRB1*12 (p = 0.028, relative risk (RR) = 2.27, 95% confidence interval (CI): 1.08-4.80) and DRB1*15 (p = 0.013, RR = 2.16, 95% CI: 1.17-4.00). They had less frequent DRB1*04 (p = 0.006, RR = 0.35, 95% CI: 0.16-0.75) compared to controls. DRB1*14 (p = 0.011, RR = 3.80, 95% CI: 1.27-11.31) were associated with the monocyclic systemic type. CONCLUSION: Korean AOSD patients had more frequent DRB1*12 and DRB1*15, and less frequent HLA-DRB1*04. The patients with the monocyclic systemic type had more frequent DRB1*14 alleles. This study suggests that Korean AOSD patients have distinct immunogenetic profiles, and that it would be valuable to assess the relationships between HLA-DRB1 genes and polymorphisms of proinflammatory cytokines in the pathogenesis of AOSD.
11858357 Fibromyalgia in Italian patients with primary Sjögren's syndrome. 2002 Jan OBJECTIVE: To assess the prevalence of fibromyalgia in primary Sjögren's syndrome and to evaluate the clinical differences between patients affected with both primary fibromyalgia and primary Sjögren's syndrome and those affected only with primary fibromyalgia. METHODS: Clinical features of fibromyalgia were evaluated in 100 consecutive outpatients with primary Sjögren's syndrome and, as controls, in 90 patients with non-insulin-dependent diabetes mellitus, in 75 patients with primary fibromyalgia and in 30 healthy subjects. RESULTS: Fibromyalgia was recorded in 22% of patients with primary Sjögren's syndrome, in 12.2% with diabetes and in 3.3% of healthy controls. In the primary Sjögren's syndrome group the prevalence was significantly higher than in healthy controls (P < 0.01), but not significantly different than in diabetes. Moreover, primary Sjögren's syndrome with fibromyalgia and primary fibromyalgia patients did not differ with respect to the number of tender points, while the mean pain threshold was lower in the latter (P = 0.05). Purpura, hypergammaglobulinemia, rheumatoid factor, and a focus score > or = 1 on lip biopsy were significantly more frequent in primary Sjögren's syndrome patients without than with fibromyalgia. CONCLUSIONS: As recently reported by other authors, our study confirms the moderate increase of fibromyalgia prevalence in primary Sjögren's syndrome. Typical fibromyalgic findings are quite similar to those of primary fibromyalgia, but surprisingly, primary Sjögren's syndrome patients with fibromyalgia show a less severe global involvement than those with primary Sjögren's syndrome alone.
14634133 Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. 2003 Dec 1 Interleukin-17 is a T cell-derived proinflammatory cytokine. This cytokine is suspected to be involved in the development of rheumatoid arthritis (RA) because this cytokine expression is augmented in synovial tissues of RA patients. The pathogenic roles of IL-17 in the development of RA, however, still remain to be elucidated. In this study, effects of IL-17 deficiency on collagen-induced arthritis (CIA) model were examined using IL-17-deficient mice (IL-17(-/-) mice). We found that CIA was markedly suppressed in IL-17(-/-) mice. IL-17 was responsible for the priming of collagen-specific T cells and collagen-specific IgG2a production. Thus, these observations suggest that IL-17 plays a crucial role in the development of CIA by activating autoantigen-specific cellular and humoral immune responses.
14600408 Participation of endogenous dehydroepiandrosterone and its sulfate in the pathology of col 2003 Nov We have investigated the serum levels of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) in type II collagen (CII)-induced arthritis (CIA) DBA/1J mice, an experimental model of human rheumatoid arthritis (RA). Serum levels of DHEA and DHEAS were measured by EIA and GC/MS, respectively. Sera were obtained from the mice on day 6, 13, 28 and 48 after the CII treatment. The disease onset of CIA was observed from day 28 (7%) to day 48 (80%) after CII immunization. The serum concentration of DHEA on day 13 did not differ from that on day 6 in CIA mice and untreated controls. Serum levels of DHEA on day 28 and 48 were significantly low compared with those on day 6 in controls. However, in CIA mice, DHEA levels on day 28 and 48 were not decreased from those on day 6. No difference in the serum DHEAS level on day 13 compared with day 6 was observed in either control or CIA mice. A significant decrease of DHEAS levels on day 28 and 48 compared with day 6 was found in both groups. The time point for the retention of DHEA in CIA mice, day 28 and day 48, coincided with the disease onset of CIA. In conclusion, endogenous DHEA may be produced as a result of physiological response for the protection against CIA.
15838107 Neuroendocrine basis of human disease. 2004 Dec This paper is a short review of the traditionally obvious diseases of neuroendocrine origin (diabetes insipidus, Kallman syndrome, etc.), but also of the newly recognized participation of several peptides originally characterized in the hypothalamus and of their receptors, in a series of diseases, both in internal medicine and in psychiatry (rheumatoid arthritis, inflammation, carcinoids, anxiety, depression, etc.). The concept of neuropeptides is now vastly expanded, as these molecules and their several receptors are now known to be widely distributed throughout the brain and the periphery with increasing evidence of paracrine and autocrine modes of action.