Factors influencing routine cognitive impairment screening in older at-risk drinkers: Findings from a qualitative study in the United Kingdom

Cognitive Impairment (CI) screening is recommended for those engaged in harmful levels of alcohol use. However, there is a lack of evidence on implementation. This paper explores the barriers and facilitators to CI screening experienced across a service specifically for older drinkers. The findings draw on data gathered as part of an evaluation of a multilevel programme to reduce alcohol-related harm in adults aged 50 and over in five demonstration areas across the United Kingdom. It is based on qualitative interviews and focus groups with 14 service providers and 22 service users. Findings are presented thematically under the section headings: acceptability of screening, interpretation and making sense of screening and treatment options. It is suggested that engagement with CI screening is most likely when its fit with agency culture and its purpose is clear; where service providers have the technical skills to administer and discuss the results of screening with service users; and where those undertaking screening have had the opportunity to reflect on their own experience of being screened. Engagement with CI screening is also most likely where specific intervention pathways and engagement practices can be accessed to respond to assessed need.     

Requirement of HMGB1 and RAGE for the maturation of human plasmacytoid dendritic cells

Dendritic cells (DC) are key components of innate and adaptive immune responses. Plasmacytoid DC (PDC) are a specialized DC subset that produce high amounts of type I interferons in response to microbes. High mobility group box 1 protein (HMGB1) is an abundant nuclear protein, which acts as a potent pro-inflammatory factor when released extracellularly. We show that HMGB1 leaves the nucleus of maturing PDC following TLR9 activation, and that PDC express on the plasma membrane the best-characterized receptor for HMGB1, RAGE. Maturation and type I IFN secretion of PDC is hindered when the HMGB1/RAGE pathway is disrupted. These results reveal HMGB1 and RAGE as the first known autocrine loop modulating the maturation of PDC, and suggest that antagonists of HMGB1/RAGE might have therapeutic potential for the treatment of systemic human diseases.     

Ambroxol inhibits interleukin 1 and tumor necrosis factor production in human mononuclear cells

We have studied the effect of Ambroxol on the production of Interleukin-1 (IL-1) and Tumor Necrosis Factor (TNF) in human mononuclear cells (MNC). For this purpose MNC were cultured for 24 h in the presence of endotoxin and different doses of Ambroxol. The results indicate that Ambroxol markedly inhibited IL-1 and TNF production at doses of 10–100 g/ml, without any apparent toxicity.     

Reduction of urinary 8-epi-prostaglandin F2α during cyclo-oxygenase inhibition in rats but not in man

1. 8-epi-prostaglandin (PG) F_2α, a major F₂ isoprostane, is produced in vivo by free radical-dependent peroxidation of lipid-esterified arachidonic acid. Both cyclo-oxygenase isoforms (COX-1 and COX-2) may also form free 8-epi-PGF_2α as a minor product. It has been recently seen in human volunteers that the overall basal formation of 8-epi-PGF_2α in vivo is mostly COX-independent and urinary 8-epi-PGF_2α is therefore an accurate marker of ‘basal'' oxidative stress in vivo.
2. To test the validity of this marker in the rat, we evaluated in vivo the effect of COX inhibition on the formation of 8-epi-PGF_2α vs prostanoids. Two structurally unrelated COX inhibitors (naproxen: 30 mg kg⁻¹ day⁻¹; indomethacin: 4 mg kg⁻¹ day⁻¹) were given i.p. to rats kept in metabolic cages. In vivo formation of 8-epi-PGF_2α was assessed by measuring its urinary excretion. Prostanoid biosynthesis was assessed by measuring urinary excretion of major metabolites of thromboxane (TX) and prostacyclin (2,3-dinor-TXB₁ and 2,3-dinor-6-keto-PGF_1α). All compounds were selectively measured by immunopurification/gas chromatography-mass spectrometry.
3. Naproxen reduced urinary excretion of 2,3-dinor-TXB₁ and 2,3-dinor-6-keto-PGF_1α but, unexpectedly, also that of 8-epi-PGF_2α (82, 49 and 52% inhibition, respectively). Indomethacin had a similar effect (77, 69 and 55% inhibition). Esterified 8-epi-PGF_2α in liver and plasma remained unchanged after indomethacin.
4. These findings prompted us to re-assess the contribution of COX activity to the systemic production of 8-epi-PGF_2α in man. We gave naproxen (1 g day⁻¹) to healthy subjects (four nonsmokers and four smokers). Urinary 8-epi-PGF_2α remained unchanged in the two groups (9.63±0.99 before vs 10.24±1.01 after and 20.14±3.00 vs 19.03±2.45 ng h⁻¹ 1.73 m⁻²), whereas there was a marked reduction of major urinary metabolites of thromboxane and prostacyclin (about 90% for both 11-dehydro-TXB₂ and 2,3-dinor-TXB₂; >50% for 2,3-dinor-6-keto-PGF_1α).
5. To investigate whether rat COX-1 produces 8-epi-PGF_2α more efficiently than human COX-1, we measured the ex vivo formation of 8-epi-PGF_2α and TXB₂ simultaneously in whole clotting blood. Serum levels of 8-epi-PGF_2α and TXB₂ were similar in rats and man.
6. We conclude that a significant amount of COX-dependent 8-epi-PGF_2α is present in rat but not in human urine under normal conditions. This implies that urinary 8-epi-PGF_2α cannot be used as an index of near-basal oxidant stress in rats. On the other hand, our data further confirm the validity of this marker in man.

     

Monoamines modulate the electrically-evoked efflux of 3H-choline from slices of guinea pig nucleus basalis magnocellularis

The influence exerted by monoamines on acetylcholine release was studied in electrically stimulated slices of guinea pig nucleus basalis magnocellularis (nbM) prelabelled with ³H-choline (3H-Ch).Noradrenaline, 30 M, and clonidine, 1 M, reduced the evoked ³H-Ch efflux by about 50%, but phenylephrine, 100 M. did not; idazoxan, 0.1 M. but not prazosin, 1 M, antagonized these effects. pointing to the involvement of alpha₂ receptors. Apomorphine, 1 or 30 M. reduced ³H-Ch efflux from nbM slices as well. The effect was shared by quinpirole, 1 or 10 M, but not by 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benz-azepine (SKF 38393). 10 M, and was antagonized by sulpiride, 1 M, but not by R-(+)-8-chloro-2,3,4,5-tetra-hydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol (SCH 23390). 1 M, suggesting the involvement of the D₂ receptor subtype.5-hydroxytryptamine (5-HT) 0.3–30 M, and alphamethyl-5-HT, 10 M, significantly increased ³H-Ch efflux from nbM slices; the 5-HT₂ antagonist ritanserin, 1 M. prevented this response. 2-methyl-5-HT, 1–30 M, inhibited the evoked ³H-Ch efflux and its effect was prevented by the 5-HT₃ antagonist 1H,3,5H-tropan-3-yl-3,5-dichlorobenzoate (MDL 72222). 1 M.These findings indicate that i) catecholamines inhibit nbM neurons through alpha₂ and D₂ receptors and that ii) a complex serotonergic modulation of cholinergic function exists in the nbM, involving the activation of various receptor subtypes. which can mediate opposite responses. Correspondence to: A. Siniscalchi at the above address     

Sporadic Duane's Retraction Syndrome Associated with Imperforate Anus: Case Report

Duane's retraction syndrome is sometimes associated with developmental ocular and extraocular abnormalities. This disorder may also be present in association with specific malformative syndromes. The authors report the clinical features of a seven-year-old female affected by Duane's retraction syndrome (D.R.S.), rectoperineal fistula, imperforate anus and other congenital malformations. From two extensive reviews of 106 reports published before 1982 and from a search (using Medline 1981-1994) for reports of congenital malformations associated with this syndrome, no cases of sporadic D.R.S. associated with the perineal malformations mentioned were found, even though imperforate anus is considered the commoner of hindgut malformation.     

State perspectives on health care reform: Oregon, Hawaii, Tennessee, and Rhode Island

The general consensus among States which have had their section 1115 demonstration projects approved is that there is no one best way to implement State health care reform. The Health Care Financing Administration (HCFA), however, wished to discern how States were accomplishing the task of implementing the demonstrations, and solicited responses from State representatives whose section 1115 demonstration waivers had been approved. The resulting article gives an overview of this implementation process from four State perspectives. Written by representatives from Oregon, Hawaii, Tennessee, and Rhode Island, the ideas presented here are indicative of the complex undertaking of State health care reform.     

Radiological aspects of osteosarcoma of the jaws

OBJECTIVES: To categorize the radiological presentation of osteosarcoma of the jaws. METHODS: Conventional radiographs and CT scans of nine patients with histologically proven osteosarcoma were reviewed. RESULTS: Five patients were men and four women, aged between 20 and 51; four lesions were in the maxilla and five in the mandible. Three radiological presentations of osteosarcoma of the jaw were identified. The first was radiolucent, characterized by a total absence of bone formation within the tumour. The second had a mottled appearance with small areas of amorphous ossification separated by non-ossified tumour tissue. The third, with lamellar ossification, was typically characterized by bony plates irradiating from a focus like a 'sunburst'. CONCLUSION: Radiological diagnosis of osteosarcoma of the jaw can be difficult because of its variable appearance. CT is particularly useful.     

High-frequency ultrasound examination of the wrist and hand

High-frequency ultrasound (US) is an efficient, rapid and inexpensive altenative to magnetic resonance imaging (MRI) for investigation of diseases in the soft tissues of the wrist and hand. US allows detection of foreign bodies and the reliable identification of a variety of traumatic lesions affecting tendons, annular pulleys, ligaments, vessels and nerves. Inflammatory diseases of tendons, including acute and chronic tenosynovitis and some degenerative conditions in the wrist and hand, can also be diagnosed. In entrapment neuropathies, US is able to identify nerve shape changes and possible extrinsic space-occupying lesions that may cause nerve compression within the tunnels. In patients with localized swelling of the hand or wrist, US is able to assess the presence of an expansile lesion and to characterize its nature in most cases. The objective of this article is to review the main findings and the primary indications of US in the investigation of disorders of the hand and wrist. Received: 10 September 1998 Accepted: 24 November 1998