Effect of biologicals and JAK inhibitors during pregnancy on health-related outcomes in children of women with inflammatory bowel disease.

Current guidelines advise to maintain immunomodulators and biologicals in pregnant patients because relapse of inflammatory bowel is associated with unfavourable pregnancy outcome. With the exception of Methotrexate, IBD therapy seems not to be related to an increase of congenital malformations or infections requiring hospitalisation of the babies, although the effect the on the developing immune system of the exposed infants remains unknown. In this review we will focus on the effect of IBD drugs on health-related outcomes in children taking into account possible long-term effects of biologicals and immunomodulators, which are transferred across the placenta.

A third of the tropical African flora is potentially threatened with extinction.

Preserving tropical biodiversity is an urgent challenge when faced with the growing needs of countries. Despite their crucial importance for terrestrial ecosystems, most tropical plant species lack extinction risk assessments, limiting our ability to identify conservation priorities. Using a novel approach aligned with IUCN Red List criteria, we conducted a continental-scale preliminary conservation assessment of 22,036 vascular plant species in tropical Africa. Our results underline the high level of extinction risk of the tropical African flora. Thirty-three percent of the species are potentially threatened with extinction, and another third of species are likely rare, potentially becoming threatened in the near future. Four regions are highlighted with a high proportion (>40%) of potentially threatened species: Ethiopia, West Africa, central Tanzania, and southern Democratic Republic of the Congo. Our approach represents a first step toward data-driven conservation assessments applicable at continental scales providing crucial information for sustainable economic development prioritization.

Continuous infusion versus intermittent flushing: maintaining peripheral intravenous access in newborn infants.

OBJECTIVE: To compare the patency duration of a peripheral intravenous cannula (PIVC) using either continuous infusion with 5% dextrose or intermittent flushing with 0.9% saline. STUDY DESIGN: Prospective comparative cohort study, including full-term newborn infants in whom PIVC were placed for the administration of antibiotics. In cohort 1 (n=48), 5% dextrose was infused at 3 ml h(-1); in cohort 2 (n=50), the cannula was flushed six times daily with 2 ml 0.9% saline. Primary outcome was the duration of PIVC patency. Secondary outcomes included the occurrence of complications, time required by the nursing staff and the cost of materials. RESULT: Duration of PIVC patency was similar. However, significantly, more complications occurred in cohort 1 (P=0.02), and both cost and time were significantly lower in cohort 2 (P=0.001). CONCLUSION: Intermittent flushing and continuous infusion provide a similar duration of PIVC patency; however, intermittent flushing is associated with fewer complications, lower cost and reduced time.

When direct health-care professional communications have an impact on inappropriate and unsafe use of medicines.

Serious safety issues relating to drugs are communicated to health-care professionals via Direct Health-Care Professional Communications (DHPCs). We explored which characteristics determined the impact of DHPCs issued in the Netherlands for ambulatory-care drugs (2001-2008). With multiple linear regression, we examined the impact on the relative change in new drug use post-DHPC of the following: time to DHPC, trend in use, degree of innovation, specialist drug, first/repeated DHPC, DHPC template, and type of safety issue. DHPCs have less impact on use of specialist drugs than nonspecialist drugs (P < 0.05). The DHPCs' impact increased after availability of a template emphasizing the main problem (P < 0.05), and for safety issues with a risk of death and/or disability (both P < 0.05) (adjusted R² = 0.392). Risk communication can be effective, specifically in case of well-structured information, and very serious safety issues. Effectiveness may improve by tailoring DHPCs and adding other communication channels, for example for drugs that are increasingly being used.

Impact of safety-related regulatory action on drug use in ambulatory care in the Netherlands.

The effect of Direct Healthcare Professional Communications (DHPCs) informing health-care providers of serious drug safety issues has been questioned. The aim of this study was to evaluate the impact of DHPCs on drug use.Nationwide dispensing data for the period 2000­2008 for new users of 46 drugs with one or more DHPCs were assessed. Impact on short-term volume of use was evaluated with regression models, and the presence of long-term changes in use was evaluated with interrupted time series analyses incorporating preexisting trends. The short-term prescription level was lower post-DHPC in 28 (48.3%) of 58 cases. Twenty (34.5%) DHPCs resulted in long-term changes in use. A long-term mean reduction in use was observed in 26.7% of cases (95% confidence interval, −15.2 to −38.2%).Long-term changes in use were not significantly related to preexisting trends in use. Although short- and long-term decreases in use were observed after only half and a third of DHPCs, respectively, the decrease was substantial.

[Limping in toddlers due to disorders of the spine and spinal cord]. / Mank lopen bij peuters door afwijkingen aan de wervelkolom en het ruggenmerg.

Limping is a frequent symptom during childhood and can be caused by a variety ofdiseases, the most common causes being trauma and infections of the bones or joints. The authors describe three cases of limping in toddlers caused by infrequent spinal diseases. The toddlers presented with limping without a preceding trauma. In the first patient, an 18-month-old girl, the limping was caused by spondylodiscitis. She recovered completely after antibiotics. The second patient, a 13-month-old boy, presented with limping caused by neuroblastoma with extensive bone metastasis. Despite chemotherapy and partial resection of the neuroblastoma, the boy did not survive. In the last patient, a 19-month-old girl, the limping was caused by an intraspinal intramedullary astrocytoma. She recovered after partial resection of the tumour. In young children presenting with limping, diagnoses involving the spine should also be considered because early intervention can influence the prognosis favourably.

[Coma in a child after treatment with the 'magic salve' lidocaine-prilocaine cream]. / Coma bij een peuter na behandeling met de 'toverzalf' lidocaine-prilocaïnecrème.

A 2-year-old girl lost consciousness after the topical application of lidocaine-prilocaine cream (EMLA) in preparation for the removal of multiple mollusca contagiosa. Both the area on which cream was applied (80% of body surface) and the total amount of cream (90 g) exceeded the maximum dosage. Lidocaine-prilocaine cream is a widely used local anaesthetic with few side effects when used properly. Intoxication with a lidocaine-prilocaine preparation may have serious consequences, such as changes in intracardiac conduction, excitation or depression of the central nervous system and methaemoglobinaemia. In our patient both methaemoglobinaemia and depression of the central nervous system occurred, resulting in loss of consciousness. She was treated with 100% oxygen and fully recovered.

[Acute rheumatic fever in children, a diagnostic problem]. / Acuut reuma bij kinderen; een diagnostisch probleem.

Three girls of Moroccan descent, aged 9, 10 and 7 years, presented with fever, joint pain and other symptoms. After Streptococcus infection and carditis were confirmed and the Jones criteria for acute rheumatic fever were met, the patients were treated with penicillin and acetylsalicylic acid. All 3 patients recovered. However, the second girl presented 2 months later with cardiac decompensation caused by valve disorders, after which aortic and mitral valvuloplasty was performed. The third girl developed joint pain again after 3 weeks and was diagnosed with juvenile idiopathic arthritis; treatment was adjusted accordingly. The prevalence of rheumatic heart diseases is 10-20 times higher in developing countries than in industrialised nations. The diagnosis 'acute rheumatic fever' should be considered in children of school age with unexplained fever, also when the Jones criteria have not yet been met. This may apply to migrant children in particular.

Pulmonary function impairment in children following hematopoietic stem cell transplantation.

BACKGROUND: Deterioration of pulmonary function after hematopoietic stem cell transplantation (SCT) is a well-known late effect of this treatment, but the course of pulmonary function over time is less clear. The aim of our study was to establish both the prevalence and course of pulmonary function abnormalities in children following SCT. METHODS: Thirty-nine of 106 patients, who visited a post-SCT late effects clinic and who underwent a pulmonary function test (PFT) both before and at least twice after SCT were included in this study. Forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), total lung capacity (TLC), and total lung diffusion capacity (TLCO) were determined and recorded as percentage predicted for age, sex, and length matched controls. Values of less than 80% of predicted were considered abnormal. Change in PFT parameters over time was determined by comparing the mean PFT parameter in our group at three different time points: pre-SCT, < or =1 year post-SCT (SCTpost1) and >1 year post-SCT (SCTpost2). RESULTS: After SCT restrictive and/or diffusion abnormalities are most prevalent (45% and 76% at SCTpost1, respectively). A significant decrease of TLC (-9.7%) and TLCO (-20.3%) was observed during the first year after SCT, with improvement over time, but no normalization. Obstructive lung disease was less common (6% at SCTpost1). Clinical signs of lung function impairment were rare. CONCLUSIONS: Restrictive and diffusion lung function disorders are common after SCT. They improve over time but do not normalize. As only a few patients with pulmonary function abnormalities had clinical signs of lung function impairment, the clinical relevance of performing long-term follow-up of PFT is questionable.

Muscle strength in patients with chronic pain.

OBJECTIVE: To analyse the influence of chronic pain on muscle strength. DESIGN: Muscle strength of patients with unilateral nonspecific chronic pain, in an upper or lower limb, were measured according to a standardized protocol using a hand-held dynamometer. Before and after muscle strength measurement, a visual analogue scale for pain intensity was assessed. RESULTS: Forty patients were measured and the muscle strength of the painful side was 20-30% less than that of the nonpainful side. Strength reduction was seen in the whole limb. A significant correlation between pain intensity and reduced muscle strength in the painful limb existed for hip flexion, knee flexion, knee extension and three-point grip. CONCLUSIONS: A strength reduction of 20-30% in a painful limb seems to be 'normal' in chronic pain patients.

Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, Org 3770 and its enantiomers.

The neurochemical and autonomic pharmacological profile of 1,2,3,4,10, 14b-hexahydro-2-methyl-pyrazino[2,1-a]pyrido[2,3-c]pyrido[2, 3-c] [2] benzazepine [+/-)Org 3770) and the related antidepressant drug, mianserin, have been compared. The uptake of [3H]noradrenaline ([3H]NA) in vitro was weakly affected by (+/-)Org 3770 (pKi = 5.6) in contrast to mianserin (pKi = 7.4). Both (+/-)Org 3770 and mianserin facilitated the release of [3H]NA in slices of cortex. The effects of NA mediated by alpha 2-adrenoceptors on the release of both [3H]NA or [3H]serotonin ([3H]5-HT) were antagonized by (+)Org 3770 with pKi values of 8.4 and 8.1, respectively. However, (-)Org 3770 only antagonized the effect of NA on the release of [3H]5-HT (pA2 = 7.7). The binding of [3H]rauwolscine to alpha 2-adrenoceptors was inhibited by (+/-)Org 3770 and mianserin with identical affinity (pKi = 7.0), whereas the binding of [3H]prazosin to alpha 1-adrenoceptors was less potently affected by (+/-)Org 3770 (pKi = 6.4) than by mianserin (pKi = 7.1). A similar difference was found for alpha 1- and alpha 2-adrenoceptors in vas deferens of the rat. The binding of [3H]mianserin to 5-HT2 receptors was less potently blocked by (+/-)Org 3770 (pKi = 8.1) than by mianserin (pKi = 9.4) while the binding of [3H]mepyramine to histamine-1 receptors was more potently affected by (+/-)Org 3770 (pKi = 9.3) than by mianserin (pKi = 8.75). The binding of [3H]quinuclidinylbenzilate to muscarinic cholinergic receptors was blocked equally by (+/-)Org 3770 (pKi = 6.1) and mianserin (pKi = 6.3). Similar data on tryptamine-D, histamine-1 and muscarinic cholinergic receptors in isolated organs were obtained. A prominent role for the blockade of alpha 2-adrenoceptors in the therapeutic effects of mianserin and (+/-)Org 3770 in depression is suggested, probably excluding a role of inhibition of the uptake of NA.

Immunohistochemical evidence for degeneration of cholinergic neurons in the forebrain of the rat following injection of AF64A-picrylsulfonate into the dorsal hippocampus.

The cholinergic neurotoxin, AF64A-picrylsulfonate, was unilaterally infused into the dorsal hippocampus of Wistar rats (2 nmol/2 microliters/4 min; A 6.2, Ls 1.5, H 6.5, Paxinos and Watson). After 19 days the for immunohistochemical staining of choline acetyltransferase (ChAT). Morphometry and counting of ChAT-immunoreactive profiles revealed shrinkage and disappearance of cholinergic neurons in the medial septum and diagonal band of Broca at the lesioned brain side. These data indicate a retrograde degeneration of cholinergic neurons following injection of AF64A-picrylsulfonate into the dorsal hippocampus of the rat.

Inhibitors of blood platelet aggregation. Activity of some 1H-benz[de]isoquinolinecarboximidamides on the in vivo blood platelet aggregation induced by collagen.

A series of 33 1H-benz[de]isoquinolinecarboximidamides has been prepared and tested in the rat after intraperitoneal (ip) and/or oral (po) administration for their ability to inhibit the in vivo blood platelet aggregation induced by collagen. In this aggregation test, a considerable number of active compounds were found. Fourteen compounds were active when administered in [0.2 (mmol/kg)/day], five of which also exhibited significant po activity. One compound was toxic after ip administration but was found to be active after po administration without apparent toxicity. It is thought that the solubility of the drug in water is an important factor for the resorption after oral administration and, hence, for its oral activity.

Presynaptic alpha-block and inhibition of noradrenaline and 5-hydroxytryptamine reuptake by a series of compounds related to mianserin.

A structure-activity relationship study was undertaken for a variety of structural analogues of the tetracyclic antidepressant mianserin. Presynaptic alpha-blocking activity in vitro was evaluated measuring the potentiation of depolarization-induced noradrenaline (NA) release from rat cerebral cortex slices. Inhibition of NA and 5-hydroxytryptamine reuptake was measured in rat hypothalamic or striatal synaptosomes, respectively. Presynaptic alpha-blockade was only found in molecules with an overall bent shape. Flat rigid molecules or flexible ones were not active. Six-membered, chair-formed D-rings (containing the -NCH3 moiety) appeared better than 5- or 7-membered ones. Heteroatom substitution, but not hydroxylation or methylation, of the bridge between the two aromatic rings left presynaptic alpha-blockade unaffected. N-Demethylation and aromatic methyl- or chlorine-substitution reduced presynaptic alpha-blockade. In pyridine ring-substituted analogues the localization of the heteroatom appeared to be crucial. 5-Hydroxytryptamine reuptake inhibitory activity was only found in desmethylmianserin. NA uptake inhibition was found in many mianserin analogues, especially those with an exocyclic-N(CH3)2 moiety. Structure activity relationships for NA reuptake inhibition differed from those for presynaptic alpha-blockade and were generally less stringent. For both properties simple additivity relationships appeared to be absent.