Chronic erosive herpes simplex virus infection of the penis, a possible immune reconstitution disease

Objective To report a novel clinical presentation: a chronic erosive herpes simplex virus (HSV) infection of the penis which developed in AIDS patients following the commencement of highly active antiretroviral therapy (HAART). The lesions were unresponsive to antiviral treatments which had previously been effective, and this could not be accounted for in terms of increased antiviral resistance.
Design Detailed case-note review and investigation of three cases which presented at two large HIV units in London.
Methods Review of all histology with immunohistochemistry for HSV, HSV drug susceptibility assays, tissue typing and measurement of in vitro lymphocyte functional activity against HSV.
Results The histology of the lesions was the same in each case, with the presence of HSV on immunohistochemistry and an unusual prominence of plasma cell and eosinophils in the inflammatory infiltrate. HSV-specific lymphoproliferative responses were normal in two cases, but subnormal in a third case. All individuals shared the HLA class I molecules B72 and Cw0202 and the class II allele DRB4.
Conclusion We believe this to be a previously unreported adverse consequence of HAART, the result of partial immune restoration, reminiscent of the the recently described syndrome of immune recovery vitritis.     

Safety findings from CENTURION,a phase 3 consistency study of lasmiditan for the acute treatment of migraine

BackgroundLasmiditan (LTN) is a selective 5-HT_1F receptor agonist for the acute treatment of migraine in adults. We present detailed safety findings from the placebo-controlled, double-blind Phase 3 study, of LTN treatment across 4 attacks (CENTURION).MethodsPatients were randomized 1:1:1 to LTN 200 mg (LTN200), LTN100, or a control group that received placebo for 3 attacks and LTN50 for either the 3rd or 4th attack (1:1). Safety analyses were conducted for patients who took ≥1 dose of study drug and, in some cases, those who took all 4 doses.ResultsOverall, 1471 patients treated 4494 attacks. The incidences of treatment-emergent serious adverse events (SAEs) were - placebo, n=2 (0.4 %); LTN100, n=1 (0.2 %); LTN200, n=2 (0.4 %); no specific treatment-emergent SAE was reported in more than one patient. The most common treatment emergent adverse events (TEAEs) with lasmiditan were dizziness, paresthesia, fatigue, nausea, vertigo, and somnolence; the vast majority were mild or moderate in severity. The incidences of these TEAEs were highest during the first attack and decreased during subsequent attacks. For patients who experienced a common TEAE with the first attack, less than 45 % experienced the same event in subsequent attacks. Patients who did not experience an event in the 1st attack infrequently experienced the same event in subsequent attacks.The time of onset of the common TEAE ranged from ~40 min to 1 h (dependent upon TEAE) and, for individual TEAE, the onset was similar across attacks. Duration was dependent upon TEAE and attack. It was shortest for paresthesia (< 2 h for all attacks); it ranged from 1.8 to 5.5 h for other common TEAEs and was generally similar across attacks.Serotonin syndrome was reported for 2 patients post LTN dosing; there were no meaningful differences across treatment groups in suicidality; there was no evidence of an increase in motor vehicle accidents.ConclusionIn this blinded, controlled, multiple-attack study, LTN was associated with generally mild or moderate CNS-related TEAEs of short duration. TEAEs tended to decrease in frequency across the 4 attacks.Trial registration {"type":"clinical-trial","attrs":{"text":"NCT03670810","term_id":"NCT03670810"}}NCT03670810 Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01343-2.     

Myocardial release of nitric oxide during ischaemia and reperfusion: effects of L-arginine and hypercholesterolaemia

AIMS: Nitric oxide (NO) may modulate myocardial ischaemia/reperfusion (I/R) injury, but effects of hypercholesterolaemia on myocardial NO release during I/R are unknown. METHODS: A NO-specific carbon fibre electrode continuously measured coronary sinus [NO] during 60 min low-flow ischaemia (1 ml/min) and 60 min free reperfusion (I/R) in isolated rabbit hearts. Experimental groups (n=7 per group) were control, L-arginine supplement (200 microM), N-nitro-L-arginine methyl ester (L-NAME) treatment (8 microM) and hypercholesterolaemic. RESULTS: During early I, NO release decreased markedly in control (-1356+/-286 pmol/min/g) and L-arginine (-1972+/-172) groups, but less in L-NAME (-441+/-89) and hypercholesterolaemic (-602+/-164) groups (both p<0.01 vs. controls). No increase in NO release during I was seen in any group. After R, NO release increased above baseline in control (+2333+/-591 pmol/min/g) and L-arginine (+1048+/-278) groups and hypercholesterolaemic (+1100+/-478) (p<0.05 vs. pre-ischaemia each group). There was little increase in NO release in the L-NAME group (+436+/-247 pmol/min/g, p<0.05 vs. controls). In each group, myocardial NO release declined towards pre-ischaemic levels during 60 min R. Hearts treated with L-arginine had similar NO release but better functional recovery than controls (p<0.01). Treatment with L-NAME was also associated with better functional recovery than in controls or hypercholesterolaemic hearts. CONCLUSION: Myocardial NO release declines rapidly during ischaemia, but increases above baseline during early reperfusion. Improved function after L-arginine treatment appears to be independent of effects upon NO release. Hypercholesterolaemia is associated with reduced myocardial NO release, under both baseline conditions and during ischaemia and reperfusion.     

Ammonium nitrate cold pack ingestion

Disposable ammonium nitrate cold packs are widely used in emergency departments instead of ice bags. Five confused or suicidal patients who tore open a pack and ingested from 64 to 234 grams of ammonium nitrate in a single dose, and another patient who attempted to do so, are reported. It is known that chronic ingestion of 6 to 12 grams/day of ammonium nitrate may cause gastritis, acidosis, isosmotic diuresis, and nitrite toxicity manifesting as methemoglobinemia or vasodilatation. None of these patients developed severe toxicity, although three had symptoms of gastritis, three had slight methemoglobinemia, and two had mild hypotension. The product was removed from the stomach promptly in three of the five patients. None had pre-existing renal or intestinal dysfunction, which are known to enhance ammonium nitrate toxicity.     

MRI快速扫描技术在儿童先天性心脏病诊断中的应用

目的:探讨MRI半傅立叶采集单次激发快速SE(HASTE)序列、真稳态进动快速成像(TrueFISP)序列和并行采集技术在儿童先天性心脏病诊断中的应用价值.方法:对50例经超声心动图检查的先天性心脏病患儿进行心脏大血管MRI检查,其中26例行DSA检查,全部病例经手术证实.扫描序列包括HASTE、TrueFISP序列以及回顾性心电门控心血管电影成像,并加用并行采集技术.分析各序列MRI图像质量,并将MRI检查结果与超声心动图、DSA结果进行对照.结果:MRI共检出10种复杂先心共181处心血管畸形.26例行DSA检查共检出畸形120个并均与手术结果吻合,MRI显示畸形114个(95.00%),超声心动图检出畸形110个(92.67%).TrueFISP序列和HASTE序列利于显示血管畸形,电影序列有助于检出心内外分流.结论:HASTE黑血技术、TrueFISP亮血技术结合快速电影序列进行心脏MRI检查,可以获得高质量的图像以及较高的病变检出率,适用于儿童先天性心脏病的诊断.     

Effectiveness of gerontologically informed nursing assessment and referral interventions for older persons attending the emergency department: systematic review

Title. Effectiveness of gerontologically informed nursing assessment and referral interventions for older persons attending the emergency department: systematic review Aim. This paper is a report of a literature review conducted to analyse data from published studies reporting nursing interventions targeted at older attendees of emergency departments (EDs), and to provide a critical appraisal of the evidence concerning their effectiveness. Background. Attendance at hospital EDs by older persons presents opportunities for targeted interventions to address actual and potential problems associated with or in addition to the presenting problem. The evidence concerning the effectiveness of such interventions is mixed. Data sources. Studies were retrieved from a systematic search of published works indexed in CINAHL, MEDLINE (PubMed), Science Direct and the Cochrane Central Register of Controlled Trials (CENTRAL). Methods. A systematic review of effectiveness was conducted using the Cochrane Effective Practice and Organisation of Care guidelines and a narrative synthesis approach for data handling and presentation. The review period was 1992 to 31 August 2008. Results. Nursing assessment and referral interventions have demonstrated effectiveness in reducing service use and improving physical function, but have failed to demonstrate statistically significant effects on predicted patient and/or health systems outcomes. Conclusion. The evidence of the effectiveness of gerontologically informed nursing assessment and referral interventions in EDs must be accepted with caution, as not all studies demonstrated effectiveness in predicted patient and/or health systems outcomes, and the testing of complex social interventions in randomized clinical trials is inherently problematic. Further evidence of the effectiveness of nursing interventions is required, and such evidence might be usefully demonstrated using pragmatic, as opposed to explanatory, trials.