Non-hemolytic transfusion reactions (NHTR) occur in up to 30% of patients receiving platelet transfusions. Premedication with acetaminophen and diphenhydramine is a common strategy to prevent NHTR, but its efficacy has not been studied. In this prospective trial, transfusions in patients receiving pre-storage leukocyte-reduced single-donor apheresis platelets (SDP) were randomized to premedication with either acetaminophen 650 mg PO and diphenhydramine 25 mg IV, or placebo. Fifty-one patients received 98 transfusions. Thirteen patients had 15 NHTR: 15.4% (8/52) in the treatment arm and 15.2% (7/46) in the placebo arm. Premedication prior to transfusion of pre-storage leukocyte reduced SDP does not significantly lower the incidence of NHTR as compared to placebo.

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Bexarotene has been reported to reduce brain amyloid-β (Aβ) levels and to improve cognitive function in transgenic mouse models of Alzheimer's disease (AD). Four groups failed to fully replicate the primary results but the original authors claimed overall support for the general conclusions. Because of its potential clinical importance, the current work studied the effects of bexarotene using two animal species and highly relevant paradigms. Rats were tested for the ability of bexarotene to prevent changes induced by an Aβ challenge in the form intracerebroventricular (i.c.v) administration of 7PA2 conditioned medium (7PA2 CM) which contains high levels of Aβ species. Bexarotene had no effect on the long-term potentiation of evoked extracellular field excitatory postsynaptic potentials induced by i.c.v. 7PA2 CM. It also had no effect following subcutaneous administration of 2, 5, 10 and 15 mg/kg on behavioral/cognitive impairment using an alternating-lever cyclic-ratio schedule of operant responding in the rat. The effects of bexarotene were further tested using the APPSwFILon, PSEN1*M146L*L286V transgenic mouse model of AD, starting at the time Aβ deposits first begin to develop. Mice were sacrificed after 48 days of exposure to 100 mg bexarotene per day. No significant difference between test and control mice was found using a water-maze test, and no significant difference in the number of Aβ deposits in cerebral cortex, using two different antibodies, was apparent. These results question the potential efficacy of bexarotene for AD treatment, even if instigated in the preclinical period prior to the onset of cognitive deficits reported for human AD. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'.

Oligomers of beta-amyloid (Aβ) are implicated in the early memory impairment seen in Alzheimer's disease before to the onset of discernable neurodegeneration. Here, the capacity of a novel orally bioavailable, central nervous system-penetrating small molecule 5-aryloxypyrimidine, SEN1500, to prevent cell-derived (7PA2 [conditioned medium] CM) Aβ-induced deficits in synaptic plasticity and learned behavior was assessed. Biochemically, SEN1500 bound to Aβ monomer and oligomers, produced a reduction in thioflavin-T fluorescence, and protected a neuronal cell line and primary cortical neurons exposed to synthetic soluble oligomeric Aβ(1-42). Electrophysiologically, SEN1500 alleviated the in vitro depression of long-term potentiation induced by both synthetic Aβ(1-42) and 7PA2 CM, and alleviated the in vivo depression of long-term potentiation induced by 7PA2 CM, after systemic administration. Behaviorally, oral administration of SEN1500 significantly reduced memory-related deficits in operant responding induced after intracerebroventricular injection of 7PA2 CM. SEN1500 reduced cytotoxicity, acute synaptotoxicity, and behavioral deterioration after in vitro and in vivo exposure to synthetic Aβ and 7PA2 CM, and shows promise for development as a clinically viable disease-modifying Alzheimer's disease treatment.

Modern travel has now brought smallpox within a day's reach of Europe and America. The acute disease should cause little trouble in diagnosis, but manifestations other than the well known rash are often forgotten or indeed unknown. Clearly radiology has no part to play in the diagnosis of acute smallpox, but the radiographic appearance of bone infection by the virus of smallpox is usually typical and diagnostic. It is important to remember that the clinical signs may be slight ; there may be little evidence of smallpox and the patient may even be unaware of any such infection. The purpose of this report is to draw attention to the changes found in osteomyelitis variolosa, and to serve as a reminder that a bone infection which fails to respond to treatment occurring in persons who have recently left a country in which smallpox is endemic may not be pyogenic in origin. The first reference to such a complication was by Bidder in 1 873. Until recently the first and only mention ofthe disease in British literature was that by Neve in 1887. The whole subject was then reviewed in detail by Cockshott and MacGregor in 1958 and 1959. A recent epidemic of smallpox in Nyasaland gave us the opportunity of studying many patients with this condition, and we made a deliberate attempt to assess its frequency and the clinical findings. Usually between 2 and 5 per cent of young children with smallpox will develop osteomyelitis variolosa (Cockshott and MacGregor 1958, Middlemiss 1962). The largest series so far reported comes from Nigeria where thirty-four cases were found during eighteen J. C. DAVIDSON AND P. E. S. PALMER to offer. Malnutrition is prevalent in the Lilongwe district and the state of nutrition of smallpox patients was assessed but no correlation between malnutrition and the incidence of smallpox was found : nevertheless the most severe cases of osteomyelitis occurred in association with anaemia and malnutrition. Because of the high incidence of sickle-cell anaemia and its association with salmonella osteitis in Nigeria, Cockshott and MacGregor AND P. E. S. PALMER THE JOURNAL OF BONE AND JOINT SURGERY (Figs. 7 and 8). Remoulding takes place extremely slowly and may require a year or more