Studies have demonstrated cross-reactivity of anti-dengue virus (DENV) antibodies in human sera against Zika virus (ZIKV), promoting increased ZIKV infection in vitro. However, the correlation between in vitro and in vivo findings is not well characterized. Thus, we evaluated the impact of heterotypic flavivirus immunity on ZIKV titers in biofluids of rhesus macaques. Animals previously infected (≥420 days) with DENV2, DENV4, or yellow fever virus were compared to flavivirus-naïve animals following infection with a Brazilian ZIKV strain. Sera from DENV-immune macaques demonstrated cross-reactivity with ZIKV by antibody-binding and neutralization assays prior to ZIKV infection, and promoted increased ZIKV infection in cell culture assays. Despite these findings, no significant differences between flavivirus-naïve and immune animals were observed in viral titers, neutralizing antibody levels, or immune cell kinetics following ZIKV infection. These results indicate that prior infection with heterologous flaviviruses neither conferred protection nor increased observed ZIKV titers in this non-human primate ZIKV infection model.

Rift Valley fever (RVF) virus (RVFV) can cause severe human disease characterized by either acute-onset hepatitis, delayed-onset encephalitis, retinitis and blindness, or a hemorrhagic syndrome. The existing nonhuman primate (NHP) model for RVF utilizes an intravenous (i.v.) exposure route in rhesus macaques (Macaca mulatta). Severe disease in these animals is infrequent, and large cohorts are needed to observe significant morbidity and mortality. To overcome these drawbacks, we evaluated the infectivity and pathogenicity of RVFV in the common marmoset (Callithrix jacchus) by i.v., subcutaneous (s.c.), and intranasal exposure routes to more closely mimic natural exposure. Marmosets were more susceptible to RVFV than rhesus macaques and experienced higher rates of morbidity, mortality, and viremia and marked aberrations in hematological and chemistry values. An overwhelming infection of hepatocytes was a major consequence of infection of marmosets by the i.v. and s.c. exposure routes. Additionally, these animals displayed signs of hemorrhagic manifestations and neurological impairment. Based on our results, the common marmoset model more closely resembles severe human RVF disease and is therefore an ideal model for the evaluation of potential vaccines and therapeutics.

SUMMARY1. Hind limb blood flow was measured in lambs of from 91 days gestation (delivered by Caesarean section) to 1 month after birth (term is about 147 days), under chloralose anaesthesia. Vascular resistance/100 g wet wt. increased progressively with age. There was reflex femoral vascular tone from the earliest age studied, as shown by vasodilatation on cutting the sciatic nerve.2. On asphyxia by cord occlusion reflex femoral vasoconstriction began earlier and was somewhat greater in older foetal lambs. At all ages, and after denervation of the hind limb, there was vasodilatation after local ischaemia, and a vasoconstriction of delayed onset during asphyxia attributed to release of noradrenaline into the circulation. The vasoconstrictor effect of noradrenaline in immature lambs was at least as great as at term or in the new-born.3. Injections of minimal effective doses of cyanide were used to localize possible chemoreceptor sites in foetal lambs. Injection into the left atrium caused a rise of arterial pressure, femoral vasoconstriction and a complex change in heart rate (usually bradycardia) but rarely any respiratory movement. After atropine, cyanide caused a large tachycardia. All responses were much reduced or abolished by cervical vagotomy.4. Injection of the same doses of cyanide into a jugular vein, the right ventricle, pulmonary or common carotid arteries of foetal lambs caused

Summary. A series of 199 patients with histologically confirmed cervical intraepithelial neoplasia (CIN) grade II or III were allocated by hospital number to receive out‐patient treatment by carbon dioxide laser vaporization or large loop excision of the transformation zone (LLETZ). All patients received local anaesthesia. The women in the LLETZ group experienced less post operative haemorrhage, less discomfort, operative time was greatly reduced, and histological material was available for confirmation of the diagnosis. There was no significant difference in recurrence of CIN after treatment between the two groups. At 6 month follow‐up, recurrence rates of 8.2% (CIN II) and 7.5% (CIN III) were observed in the laser‐group and 5% (CIN II) and 5.3% (CIN III) in the LLETZ group. Further advantages of LLETZ are reduced capital expenditure and no hazard to the eyesight of the surgeon, but laser treatment is preferable in patients with widespread vaginal involvement.

SUMMARY1. In foetal lambs the effect of raising and lowering arterial Po2 (by varying the 02 content of the maternal inspired gas mixture) was studied in order to determine whether the systemic arterial chemoreceptors regulated the circulation.2. From 0 7 of term relative hypoxaemia (e.g. reducing carotid Po. from 40 to 20 mm Hg) caused a rise of arterial pressure and femoral vasoconstriction. These changes were unaffected or even increased by bilateral section of the nerves from the carotid sinus and body. They were abolished by section of the vagi or aortic nerves.3. It is concluded that in foetal lambs during the last third of gestation the circulation is under reflex control by the aortic chemoreceptors.