Flemish network on rare connective tissue diseases (CTD): patient pathways in systemic sclerosis. First steps taken.

Despite the low prevalence of each rare disease, the total burden is high. Patients with rare diseases encounter numerous barriers, including delayed diagnosis and limited access to high-quality treatments. In order to tackle these challenges, the European Commission launched the European Reference Networks (ERNs), cross-border networks of healthcare providers and patients representatives. In parallel, the aims and structure of these ERNs were translated at the federal and regional levels, resulting in the creation of the Flemish Network of Rare Diseases. In line with the mission of the ERNs and to ensure equal access to care, we describe as first patient pathways for systemic sclerosis (SSc), as a pilot model for other rare connective and musculoskeletal diseases. Consensus was reached on following key messages: 1. Patients with SSc should have multidisciplinary clinical and investigational evaluations in a tertiary reference expert centre at baseline, and subsequently every three to 5 years. Intermediately, a yearly clinical evaluation should be provided in the reference centre, whilst SSc technical evaluations are permissionably executed in a centre that follows SSc-specific clinical practice guidelines. In between, monitoring can take place in secondary care units, under the condition that qualitative examinations and care including interactive multidisciplinary consultations can be provided. 2. Patients with early diffuse cutaneous SSc, (progressive) interstitial lung disease and/or pulmonary arterial hypertension should undergo regular evaluations in specialised tertiary care reference institutions. 3. Monitoring of patients with progressive interstitial lung disease and/or pulmonary (arterial) hypertension will be done in agreement with experts of ERN LUNG.

Needle arthroscopy of the knee with synovial biopsy sampling: technical experience in 150 patients.

Needle arthroscopy is an office-based technique allowing direct visualisation of the knee cavity and selective sampling of the synovial membrane. We performed needle arthroscopy in 150 patients with synovitis of the knee (1) to evaluate the diagnostic potential in early arthritis, (2) to perform therapeutic lavage in persistent inflammatory synovitis and (3) to assess the balance between technical feasibility, safety and patient comfort on the one hand, and the relevance of the obtained macro- and microscopic information for diagnosis and research purposes on the other. After disinfection of the leg and local anaesthesia of the skin and joint, a 1.8-2.7 mm needle arthroscope was introduced into the knee. Synovial fluid was aspirated and lavage of the joint cavity was performed to allow macroscopic evaluation of hyperaemia and hypertrophy of the synovial membrane. Biopsies were taken at inflamed sites, followed by another lavage to remove blood and debris. Needle arthroscopy of the knee is a simple and easy to perform technique made particularly attractive by the local anaesthesia and the ambulatory setting. It allows good macroscopic evaluation of synovial inflammation and selective sampling of the synovial membrane. Biopsies are suitable for RNA and DNA extraction, bacterial or lymphocyte culture, and cell isolation. Because samples were sometimes too small for representative histology, we switched from a 1.8 mm to a 2.7 mm biopsy forceps with good results. In nearly all cases the arthroscopy was well tolerated. Moreover, some patients reported relief of symptoms and even improvement of mobility after lavage of the inflamed joint. No major complications were noted. It was concluded that needle arthroscopy of the knee is a simple, safe and well-tolerated technique, with promising perspectives as a diagnostic, scientific and possibly therapeutic tool in rheumatic diseases.

Endocrine communication between conceptus and mother: placental lactogen stimulation of maternal behavior.

The possible role of the conceptus in stimulating the onset of maternal behavior through its secretion of placental lactogens and their passage into the brain was investigated in female rats. In the first study, significant mitogenic activity in the Nb2 lymphoma cell bioassay was detected in cerebrospinal fluid (CSF) samples collected by push-pull perfusion from rats on days 12-21 of pregnancy, coincident with the establishment of placental function. In contrast, mitogenic activity was absent from CSF in lactating and gonadectomized, virgin females. In a second study the mitogenic activity in day 12 pregnant samples was neutralized 71% with antibodies to rat placental lactogen-I (rPL-I) and > 90% with a combination of antibodies to rPL-I plus rPL-II. In contrast, activity on day 21 of pregnancy, 1 day prepartum, was reduced by antibodies to rPL-II (> 85%), but not by antibodies to rPL-I, indicating that the predominant lactogen in the CSF prepartum is rPL-II. The behavioral actions of placental secretions were assessed in the third experiment by infusing recombinant rPL-I and purified rPL-II directly into the medial preoptic area of the brain of steroid-primed, nulliparous rats. Latencies to respond maternally to foster young were significantly reduced in rPL-I- and rPL-II-treated rats (2- to 3-day latencies) when compared with latencies in control females (5- to 6-day latencies). Thus, the conceptus through its secretion of rPLs which apparently gain access to the CSF helps to prime the pregnant female's brain to respond maternally at the end of gestation. This endocrine communication between the developing conceptus and pregnant female appears to be an important part of the biological system which helps to establish successful maternal care.

Lymphocytic gastritis. Clinical and endoscopic presentation and long-term follow-up.

Lymphocytic gastritis is a histopathological entity corresponding with diffuse varioliform gastritis but also with other gastroscopic findings. Eighteen patients were followed over a mean period of 25 months. The symptoms, the endoscopic and histopathological abnormalities remained unchanged in the majority of the cases. Conventional peptic ulcer therapy failed to control symptoms or to normalize endoscopic alterations. Helicobacter pylori did not seem to play a role in the pathophysiology. Lymphocytic duodenitis was found in four patients. The relationship between lymphocytic gastritis, Ménétrier's disease and coeliac disease has further to be elucidated.

Prior parity reduces post-coital diurnal and nocturnal prolactin surges in rats.

Mating stimuli received by female rats activate a neuroendocrine mnemonic system which produces daily diurnal and nocturnal prolactin (PRL) surges for the first half of gestation, surges which help maintain corpora lutea function and a viable pregnancy. Since these PRL surges may be regulated in part by endogenous opioids and opioid sensitivity declines as a function of multiple births, we decided to investigate the possibility that prior parity might affect the post-coital diurnal and nocturnal PRL surges, reducing their magnitude and/or occurrence. Age-matched, nulliparous and primiparous rats were mated to males from our colony. On days 5 or 10 of pregnancy females received jugular catheters. Blood samples were collected at regular intervals from 1000 h on day 7 to 1000 h on day 8, and from 1000 h on day 12 to 1000 h on day 13 of gestation in separate sets of multigravid and primigravid rats. Measurement of plasma PRL by radioimmunoassay revealed that prior reproductive experience altered the patterns and levels of plasma PRL. Plasma PRL levels were significantly reduced during both the diurnal and nocturnal surges on days 7-8 in multigravid rats when compared with levels in primigravid rats. No differences in PRL levels were found between primigravid and multigravid groups on days 12 to 13 of gestation. The changes in diurnal and nocturnal PRL surges during early pregnancy indicate that prior parity reduces the subsequent secretion of PRL, possibly by altering the neuroendocrine regulation of this hormone.