5-HYDROXYTRYPTAMINE-INDUCED CONTRACTION OF THE MARMOSET AORTA IS MEDIATED BY A 5-HT1-LIKE RECEPTOR

1. 5-Hydroxytryptamine (5-HT) exerts both contractile and relaxant effects in the marmoset isolated aorta, actions that are unaffected by the 5-HT₂ antagonist ketanserin. The aim of the present study was to define the receptors mediating the contractile activity of 5-HT in the marmoset aorta.
2. Contractile responses were elicited in aortic rings that were either: (i) precontracted submaximally with the thromboxane A₂ agonist U44069 in order to amplify the responses; or (ii) exposed to N ^ω-nitro- L -arginine (100 μmol/L) plus LY 53857 (0.1 μmol/L; a 5-HT₂ receptor antagonist shown previously to inhibit relaxation). The effect of 5-HT on adenosine 3',5'-cyclic monophosphate (cAMP) formation was also investigated.
3. The effects of agonists and antagonists comprised: (i) agonist potencies in the order 5-carboxamidotryptamine > 5-HT > sumatriptan > 8-hydroxy-2-(di- n -propylamino)tetralin; (ii) inhibition of contractile action of 5-HT by the 5-HT_1D antagonist GR 127935; (iii) a contractile response to methysergide; (iv) a lack of effect of tropisetron, an antagonist of 5-HT₃ and 5-HT₄ receptors; and (v) inhibition of forskolin-stimulated cAMP formation by 5-HT (in the presence of LY 53857), indicative of negative coupling to adenylate cyclase.
4. The above effects fulfil the criteria for a 5-HT₁-like receptor. In view of the previous finding that this contractile response is insensitive to ketanserin, it is concluded that the contractile effects of 5-HT in the marmoset aorta are mediated exclusively by a 5-HT₁-like receptor.     

Risk of Guillain-Barré syndrome after measles-mumps-rubella vaccination

OBJECTIVE: To assess the postulated causal association between measles-mumps-rubella (MMR) vaccination and Guillain-Barré syndrome (GBS). STUDY DESIGN: Active retrospective study based on linkage of the nationwide hospital discharge register with individual vaccination records. All patients hospitalized for treatment of GBS in Finland between November 1982 and December 1986 were included in the study. RESULTS: During the study period, 189 patients were hospitalized for treatment of GBS, and approximately 630,000 vaccine recipients received 900,000 doses of MMR vaccine; 24 of the 189 patients represented the prevailing target population for MMR vaccination, of whom 20 were vaccinated. MMR vaccination did not cause any increase over the background incidence of GBS, and no clustering of cases of GBS occurred at any time point after administration of MMR vaccine. The interval between vaccination and onset of symptoms of GBS exceeded the designated risk period of 6 weeks in all cases, varying from 80 days to years. MMR vaccination after recovery from GBS did not cause relapses of the illness. Respiratory or gastrointestinal tract infection predated the onset of GBS by 3 to 30 days in 20 (83%) of the 24 patients. CONCLUSIONS: No causal association seems to prevail between MMR vaccination and GBS.     

Bile duct obstruction: radiologic evaluation of level, cause, and tumor resectability

In a prospective study of 65 patients with bile duct obstruction, various radiologic modalities were compared for their capability to demonstrate the level and cause of obstruction and to indicate accurately tumor resectability. Ultrasound (US) was performed in 65 patients, computed tomography (CT) in 51, direct cholangiography (DC) in 57, and angiography in 35. The level of obstruction was correctly indicated by US in 95% of patients and by CT in 90%, and the cause was correctly indicated by US in 88%, by CT in 63%, and by DC in 89%. In predicting tumor resectability, US was correct in 71% of patients, compared with 42% for CT, 58% for DC, and 25% for angiography. US therefore appears to be the single most useful modality in the evaluation bile duct obstruction.     

Data warehouse approach to nursing management

AIM: This article describes a data warehouse approach when designing an information system to meet nursing management needs in acute hospital setting. BACKGROUND: The rapidly changing health care environment has created new challenges for nursing leaders and requires appropriate, accurate and timely data for decision-making. METHOD: Key aspects of current information needs were identified by a nursing expert group. A data warehouse-based Nursing Management Information System was produced and piloted in nine wards. A survey and interviews were conducted to evaluate the piloting. RESULTS: Data from the patient administrative system together with nursing rostering data and measures for nursing care intensity brought new opportunities for nursing management. CONCLUSIONS: A Nursing Management Information System is suggested to be built using data warehouse model. Successful implementation of a Nursing Management Information System requires systematic data quality checks. An information analyst is essential for interpreting and communicating nursing data to multi-professional management groups.     

The place of premedication in pediatric practice

Behind the multiple arguments for and against the use of premedication, sedative drugs in children is a noble principle that of minimizing psychological trauma related to anesthesia and surgery. However, several confounding factors make it very difficult to reach didactic evidence-based conclusions. One of the key confounding issues is that the nature of expectations and responses for both parent and child vary greatly in different environments around the world. Studies applicable to one culture and to one hospital system (albeit multicultural) may not apply elsewhere. Moreover, the study of hospital-related distress begins at the start of the patient's journey and ends long after hospital discharge; it cannot be focused completely on just the moment of anesthetic induction. Taking an example from actual practice experience, the trauma caused by the actual giving of a premedication to a child who absolutely does not want it and may struggle may not be recorded in a study but could form a significant component of overall effect and later psychological pathology. Clearly, attitudes by health professionals and parents to the practice of routine pediatric premedication, vary considerably, often provoking strong opinions. In this pro–con article we highlight two very different approaches to premedication. It is hoped that this helps the reader to critically re-evaluate a practice, which was universal historically and now in many centers is more selective.     

p38alpha and p38delta mitogen-activated protein kinase isoforms regulate invasion and growth of head and neck squamous carcinoma cells

Recent studies indicate that the specificity of p38 mitogen-activated protein kinase (MAPK)-mediated cellular stress responses is determined by the expression pattern of the distinct p38 isoforms. Here, we have analysed the function of distinct p38 isoforms in the growth and invasion of head and neck squamous cell carcinomas (HNSCCs). Activation of p38 MAPK by arsenite resulted in inactivation of the ERK1,2 signaling pathway by dephosphorylation of MEK1,2 in primary human epidermal keratinocytes (HEKs), whereas in HNSCC cells this p38-mediated inhibition of the ERK1,2 pathway was absent. Quantitation of p38 pathway component mRNA expression in HNSCC cell lines (n=42) compared to HEKs (n=8) revealed that p38alpha and p38delta isoforms are predominantly expressed in both cell types and that MKK3 is the primary upstream activator expressed. Inhibition of endogenous p38alpha or p38delta activity by adenoviral delivery of corresponding dominant-negative p38 isoforms potently reduced MMP-13 and MMP-1 expressions, and suppressed the invasion of HNSCC cells through collagen. Dominant-negative p38alpha and p38delta inhibited squamous cell carcinoma (SCC) cell proliferation and inhibition of p38alpha activity also compromised survival of SCC cells. p38alpha and p38delta were predominantly expressed in HNSCCs (n=24) and nonneoplastic epithelium in vivo (n=6), with MKK3 being the primary upstream activator. Activation and expression of p38alpha and p38delta by tumor cells was detected in HNSCCs in vivo (n=16). Adenoviral expression of dominant-negative p38alpha or p38delta in cutaneous SCC cells potently inhibited their implantation in skin of severe combined immunodeficiency mice and growth of xenografts in vivo. Our results indicate that p38alpha and p38delta specifically promote the malignant phenotype of SCC cells by regulating cell survival, proliferation and invasion, suggesting these p38 MAPK isoforms as potential therapeutic targets in HNSCCs.     

Distribution of acidic fibroblast growth factor-like immunoreactivity in rat skeletal muscle fibers

Acidic fibroblast growth factor (aFGF) is a mitogenic, angiogenic and neurotrophic growth factor which promotes proliferation, but delays differentation of cultured myoblasts. Its mRNA is expressed in the skeletal muscle, however the distribution of aFGF in the postnatal skeletal muscle is poorly characterized. In the present study, the distribution of aFGF-like immunoreactivity (LI) was examined in developing and adult rat skeletal muscle fibers. In addition, the effect of the transection of the sciatic nerve on aFGF-LI in calf muscle fibers was examined. From the first postnatal day on, aFGF-immunoreactive (IR) muscle fibers were observed in different calf muscles. From the 7th postnatal day on a large number of muscle fibers exhibited aFGF-LI in the soleus muscle, some in plantaris and only few in gastrocnemius and extraocular muscles. Double-labelling with fast-myosin antibody showed that aFGF-LI was restricted to the slow oxidative muscle fibers. aFGF-IR intrafusal muscle fibers were seen in developing and mature muscle spindles. In addition, aFGF-IR nerve fibers and myoneural junctions were observed in different muscles. Transection of the sciatic nerve did not noticeably alter the expression pattern of aFGF-L[ in calf muscles during two-week period.The present study demonstrates aFGF-LI in the rat slow oxidative muscle fibers where it may have fiber-type specific functions in addition to its known trophic effects.