During the oxidative degradation of 2,4-dimethylaniline (2,4-xylidine) by means of the H2O2/UV method, a series of hydroxylated aromatic amines are formed, this result confirming the role of the hydroxyl radical as an initiator of the oxidative chain reaction. Thermal or photochemically enhanced Fenton reactions in the presence of 2,4-dimethylaniline (2,4-xylidine) yield primarily 2,4-dimethylphenol as an intermediate product, the genesis of which may only be explained by an electron transfer mechanism. Experimental evidence for such a mechanism is presented, and values for the quantum yields of the photochemically enhanced reduction of iron(III) to iron(II) in aqueous solutions of 2,4-xylidine are given.

Background: The association between sympathetic activation and mortality in chronic heart failure and the favorable effect of beta blocking drugs has raised the possibility of therapeutic efficacy for central sympathetic inhibition with sustained-release (SR) moxonidine, an imidazoline receptor agonist. Methods: A randomized double-blind, placebo-controlled trial was initiated in 425 centers in 17 countries with a plan to enter 4533 patients with New York Heart Association class II-IV heart failure and a reduced ejection fraction. Moxonidine SR or matching placebo was titrated to a target dose of 1.5 mg BID. The trial was powered to detect a 20% reduction in mortality, which required a total of 724 deaths. Findings: An early increase in death rate and adverse events in the moxonidine SR group led to premature termination of the trial because of safety concerns after 1934 patients were entered. Final analysis revealed 54 deaths (5.5%) in the moxonidine SR group and 32 deaths (3.4%) in the placebo group during the active treatment phase. Survival curves revealed a significantly (Ps0.012) worse outcome in the moxonidine SR group. Hospitalization for heart failure, acute myocardial infarction and adverse events were also more frequent in the moxonidine SR group. Plasma norepinephrine was significantly decreased by moxonidine SR (y18.8% from baseline) vs. placebo (q6.9%). Interpretation: Early termination of the trial limited conclusions regarding the long-term effects of central sympathetic inhibition. Nonetheless, the excess early mortality and morbidity suggest the likelihood of an adverse effect of moxonidine SR and raise concerns regarding the efficacy of generalized sympathetic inhibition in heart failure.

Background: Since May 2022, increasing numbers of monkeypox virus (MPXV) infections have been reported from across Europe and North America.Studies, mainly from Africa, have suggested a higher risk for severe MPXV cases in people living with HIV.Methods: This was a retrospective study of all confirmed MPXV infections observed in the participating centres since 19 May 2022. We conducted a chart review to evaluate clinical characteristics, comorbidities, and coinfections, including HIV, viral hepatitis, and sexually transmitted infections (STIs). Results: By 30 June 2022, a total of 546 MPXV infections were reported from 42 German centres. All patients were men who have sex with men (MSM), of whom 256 (46.9%) were living with HIV, mostly with a preserved immune system and with viral suppression. In total, 232 (42.5%) MSM were also taking HIV pre-exposure prophylaxis (PrEP) and 58 (10.6%) MSM had no known HIV infection or PrEP use. The median age was 39 years (range 20-67), and comorbidities were rare. However, 52.4% and 29.4% of all patients had been diagnosed with at least one STI within the last 6 months or within the last 4 weeks, respectively. The most frequent localizations of MPXV infection were For affiliation refer to page 395

Background-In chronic heart failure, sympathetic activation is increased. Moxonidine acts on central nervous system receptors to decrease sympathetic activation. We investigated the dose-response relationship of a new sustained-release (SR) preparation of moxonidine and the plasma concentration of norepinephrine in patients with chronic heart failure. Methods and Results-A total of 268 patients with chronic heart failure in NYHA functional class II to IV on optimal standard therapy were randomized to placebo or 1 of 5 doses of moxonidine SR: 0.3, 0.6, 0.9, 1.2, or 1.5 mg BID. After a dose-titration phase (7 weeks), patients were followed up for another 12 weeks at their maximally tolerated dose. Blood samples for plasma norepinephrine were collected at baseline and weekly during the initial 7 weeks, at week 19, and at the end of the study. At baseline and 7 and 19 weeks, sampling was also done 4 hours after the dose. After the active phases of the study, plasma norepinephrine was evaluated for an additional 3 days. A marked, statistically significant dose-related decrease in plasma norepinephrine was observed for predose levels as well as 4 hours after the dose at week 19. At the highest dose (1.5 mg BID), the trough reduction in norepinephrine was 52%. These reductions were accompanied by a modest decrease in heart rate, a modest increase in left ventricular ejection fraction, and a dose-related increase in adverse events. Conclusions-Plasma norepinephrine was markedly reduced in a dose-related manner by moxonidine SR. This reduction was accompanied by evidence of reverse remodeling, but also by an increase in adverse events.

Tedisamil at dosages of 0.4 and 0.6 mg/kg was superior to placebo in converting AF or AFL. Tedisamil has a rapid onset of action leading to conversion within 30 to 40 min in the majority of responders.