Epstein-Barr virus genome load is increased by therapeutic vaccination in HIV-l carriers, and further enhanced in patients with a history of symptomatic primary infection

Objective

Epstein–Barr virus (EBV) infection is an established risk factor for B-cell lymphomas in Human Immunodeficiency virus (HIV)-1 infected patients. A disturbed EBV-host relationship is seen in patient groups with a high risk for EBV-associated lymphomas. We have analysed this relationship by measuring EBV-DNA in the blood of HIV-1 carriers.

Method

EBV-DNA load in B-cells was monitored by PCR in non- or insufficiently antiretroviral treated and rgp160-vaccinated HIV-patients.

Results

Both asymptomatic HIV-infected and AIDS-patients showed a 25–40-fold increase in the number of B cell associated EBV-DNA copies compared to healthy controls. Patients included in a vaccine trial with recombinant HIV gp160 showed a 5-fold increase of EBV load compared to non-immunised patients and a 50-fold increase compared to healthy controls. There was no difference whether they received vaccine or “placebo”. Vaccinated patients with a history of symptomatic primary HIV-1 infection (PHI) had a 280-fold increase in median EBV load compared to healthy controls, thus suggesting a synergistic effect between the vaccination and PHI, which hypothetically could affect lymphoma risk.

Conclusions

We recommend analysis of EBV-load and long term follow up of lymphoma risk in all therapeutic HIV-1 vaccination trials.     

Targeting the oxytocin receptor to relax the myometrium

Oxytocin acting via its receptor is involved in the myometrial hyperactivity of preterm labour and possibly also in that of primary dysmenorrhoea. The closely related hormone vasopressin acting on its uterine receptor of type V1a may also contribute to the myometrial hyperactivity of these conditions. Several pharmaceutical compounds inhibiting these receptors are, therefore, under development and one substance, atosiban, has now been registered in many countries for the treatment of preterm labour. This compound blocks both the oxytocin and the vasopressin V1a receptor. The efficacy is at least as pronounced as that of other types of drugs and side effects are much reduced. In this overview, present knowledge about receptor-mediated effects of oxytocin and vasopressin on myometrial activity is summarised. Furthermore, the therapeutic use of oxytocin and vasopressin V1a receptor antagonists in preterm labour and primary dysmenorrhoea is discussed.     

The effect of relcovaptan (SR 49059), an orally active vasopressin V1a receptor antagonist, on uterine contractions in preterm labor.

Relcovaptan (SR 49059) is a non-peptide, orally active vasopressin V1a receptor inhibitor. The effect on uterine contractions in 18 women with preterm labor in pregnancy weeks 32-36 was assessed in a double-blind investigation. The inclusion criterion was at least four regular uterine contractions over 30 min as measured by external tocodynamometry. Twelve patients received at random a single oral dose of 400 mg relcovaptan and six received placebo, and contractions were monitored up to 6 h thereafter. Rescue medication (beta-adrenoceptor-stimulating drug) was allowed after 2 h. Before drug administration a mean (+/- SE) of 8.2 +/- 1.4 and 9.7 +/- 1.6 contractions/30 min were recorded in the relcovaptan- and placebo-treated groups, respectively. In the former group, the frequency of uterine contractions started to decrease within the first half hour, and 1.5-2 h after dosing it was steady at 3.2 +/- 0.9 contractions/30 min. Correspondingly, after placebo, 7.8 +/- 2.2 contractions/30 min were recorded, a statistically significant difference (p = 0.017). The activity in the relcovaptan-treated women remained low, whereas in the placebo group inhibited uterine contractions were observed only in women receiving 'rescue' tocolytic treatment. It is concluded that relcovaptan inhibits preterm labor.     

Nasal mucosal temperature and the effect of acute infective rhinitis

Nasal mucosal temperature was measured in 71 healthy subjects with an electronic thermometer. No correlation was found between the nasal mucosal temperature and age or sex. An increased mucosal temperature was found in patients with acute rhinitis, an effect which is supposed to assist in the defence system against microorganisms. When measuring nasal mucosal temperature over a 7-h period at the same time as nasal airway resistance, there was no correlation between these factors, indicating that the temperature is independent of the state of the capacitance vessels.     

Vasotocin analogues which competitively inhibit vasopressin stimulated uterine activity in healthy women

Three analogues of posterior pituitary hormones, 1-deamino-2-D-Tyr(OEt)-4-Val-8-Orn-vasotocin(dE-VVT), 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-vasotocin(dE-TVT) and 1-deamino-2-D-Tyr(OEt)-oxytocin(dE-OXY) were compared for their inhibitory effects on vasopressin (VP)-induced uterine activity in healthy women. At menstruation, during recording of intrauterine pressure (18 recording sessions in 11 women), intravenous infusion of lysine vasopressin (LVP, 1 ng/min/kg/body weight) induced an increase of the uterine activity and dysmenorrhoea-like symptoms. Intravenous injections of all analogues (10 micrograms/kg body weight) caused relief of symptoms and inhibition of uterine activity, dE-TVT was the most effective and dE-OXY was least active. With dE-TVT almost complete inhibition of contractions was seen during the first 10 min after injection. The duration of effect was also greatest with that analogue (40-50 min). Only dE-OXY had an agonist effect on spontaneous uterine activity. Pharmacokinetic studies of intravenous dE-TVT (10 ng/kg body weight) showed that the plasma half-life was approximately 16 min and the clearance 30 l/h. The bioavailability of 100 ng/kg given intranasally was about 5.5%. Further studies are recommended.     

4p16.3 haplotype modifying age at onset of Huntington disease

Huntington disease (HD) is caused by an expanded CAG repeat sequence in the HD gene. Although the age at onset is correlated to the CAG repeat length, this correlation only explains approximately half of the variation in onset age. Less variation between siblings indicates that the variation is, in part, explained by genetic modifiers. We analyzed polymorphic loci within or close to the HD gene on the HD chromosome in Danish HD patients. We found one specific haplotype segregating with later age at onset, compared with patients with similar CAG repeat length and another haplotype. The nine Danish families in the study carrying this haplotype most likely have a common founder. Several of the polymorphic loci displayed alleles that may be specific to the late-onset haplotype, implicating that from this study we cannot determine which of the loci tested (or other polymorphic loci in this chromosomal area) do in fact contain genetic modifiers of age at onset.     

Water and electrolyte absorption in ileal segments surgically transposed to the urinary bladder in the cat

Net transport of water and electrolytes was studied in ileal segments which had been exposed to urine during three months in seven cats. During surgery, a 5 cm long ileal segment was interposed between the ureters and the urinary bladder. At the same time a control segment (5 cm) was indicated with silver clips. After three months, the net transport of water and electrolytes was studied using a continuous perfusion technique with an isotonic and with a hypertonic, urine-like perfusate. Microscopic examination of the mucosa showed a significant reduction of villus height in the transposed segments compared to the controls (p less than 0.05). With the isotonic perfusate there was a net absorption of water in the control segments, and a net secretion in the transposed segments, the difference being statistically significant (p less than 0.05). When the hypertonic perfusate was used, a net secretion occurred in both control and transposed segments. Net transport of electrolytes (Na+, K+, Cl-) was in the same direction as water transport in both control and transposed segments. The results indicate that there does not seem to be any risk of water or electrolyte reabsorption by intestinal mucosa which has been exposed to urine.     

Gastric ulcer disease in infants: US findings

Among 600 infants examined with ultrasound for vomiting, seven (mean age, 3 months) had distinctive features that can be considered diagnostic of gastric ulcer. The findings are thickening of the mucosa (greater than 4 mm) in the antropyloric region, elongation of the antropyloric canal, persistent spasm, and delayed gastric emptying. Two of the infants had slight thickening of the pyloric muscle. Gastrointestinal series or endoscopy demonstrated thickened gastric mucosa and a deformed gastric antrum in all infants, as well as actual ulceration in five.