Michael Bray

Rupture of the ascending aorta during cocaine intoxication

Abstract Cocaine is commonly injected, sniffed and smoked because of its psychotropic effects, but it also has significant cardiovascular effects. Illicit use of cocaine has been associated with ventricular arrhythmias, myocardial infarction, with or without associated significant coronary atherosclerosis, and subarachnoid hemorrhage. 1–4 Herein, we describe rupture of the ascending aorta in a person while smoking cocaine, a complication of cocaine use not previously described.

Dengue virus premembrane and membrane proteins elicit a protective immune response

We have constructed recombinant vaccinia viruses that express the premembrane (pre-M), membrane (M), or the cleaved, residual portion of pre-M (non-M) proteins of dengue 4 virus, or the pre-M, non-M, or envelope (E) proteins of dengue 2 virus, to evaluate their ability to induce protective immunity in mice. Cells infected with these recombinants make proteins of expected size. Mice immunized with recombinants expressing dengue 4 pre-M or M were protected against subsequent dengue 4 encephalitis challenge, but non-M was not protective. However, a recombinant that expressed both pre-M and E as a polyprotein gave solid protection, while the simultaneous administration of the two recombinants expressing pre-M and E gave a significant level of protection. Pre-M and M function as antigens eliciting a protective immune response, and the combination of pre-M plus E is more protective than E alone.

Tick-Borne Langat/Mosquito-Borne Dengue Flavivirus Chimera, a Candidate Live Attenuated Vaccine for Protection against Disease Caused by Members of the Tick-Borne Encephalitis Virus Complex: Evaluation in Rhesus Monkeys and in Mosquitoes

ABSTRACT Langat virus (LGT), strain TP21, a naturally avirulent tick-borne flavivirus, was used to construct a chimeric candidate virus vaccine which contained LGT genes for premembrane (preM) and envelope (E) glycoprotein and all other sequences derived from dengue type 4 virus (DEN4). The live virus vaccine was developed to provide resistance to the highly virulent, closely related tick-borne flaviviruses that share protective E epitopes among themselves and with LGT. Toward that end the chimera, initially recovered in mosquito cells, was adapted to grow to high titer in qualified simian Vero cells. When inoculated intraperitoneally (i.p.), the Vero cell-adapted LGT TP21/DEN4 chimera remained completely attenuated for SCID mice. Significantly, the chimera protected immunocompetent mice against the most virulent tick-borne encephalitis virus (TBEV). Subsequently, rhesus monkeys were immunized in groups of 4 with 105 or 107 PFU of LGT strain TP21, with 105 PFU of DEN4, or with 103, 105, or 107 PFU of the chimera. Each of the monkeys inoculated with DEN4 or LGT TP21 became viremic, and the duration of viremia ranged from 1 to 5 days. In contrast, viremia was detected in only 1 of 12 monkeys inoculated with the LGT TP21/DEN4 chimera; in this instance the level of viremia was at the limit of detection. All monkeys immunized with the chimera or LGT TP21 virus developed a moderate to high level of neutralizing antibodies against LGT TP21 as well as TBEV and were completely protected against subsequent LGT TP21 challenge, whereas monkeys previously immunized with DEN4 virus became viremic when challenged with LGT TP21. These observations suggest that the chimera is attenuated, immunogenic, and able to induce a protective immune response. Furthermore, passive transfer of serum from monkeys immunized with chimera conferred significant protection to mice subsequently challenged with 100 i.p. 50% lethal doses of the highly virulent TBEV. The issue of transmissibility of the chimera by mosquitoes was addressed by inoculating a nonhematophagous mosquito,Toxorhynchites splendens, intrathoracically with the chimera or its DEN4 or LGT parent. Neither the LGT TP21/DEN4 vaccine candidate nor the wild-type LGT TP21 virus was able to infect this mosquito species, which is highly permissive for dengue viruses. Certain properties of the chimera, notably its attenuation for monkeys, its immunogenicity, and its failure to infect a highly permissive mosquito host, make it a promising vaccine candidate for use in immunization against severe disease caused by many tick-borne flaviviruses.

Aberrant thyroid gland attached to ascending aorta

Abstract R.D., a 47-year-old man, died of intracerebral hemorrhage soon after injecting heroin into a vein. Necropsy disclosed cardiomegaly (heart weight 450 g) without cavity dilatation or myocardial foci of fibrosis or necrosis. A brownish red nodule that measured 3 × 2.3 × 1.5 cm and weighed about 15 g was attached to the adventitia of the ascending aorta (Fig. 1).