Positive follow-up blood cultures identify high mortality risk among patients with Gram-negative bacteraemia.

OBJECTIVES: The role of follow-up blood cultures (FUBCs) in the management of Gram-negative bacteraemia (GNB) is poorly understood. We aimed to determine the utility of FUBCs in identifying patients with increased mortality risk. METHODS: An observational study with a prospectively enrolled cohort of adult inpatients with GNB was conducted at Duke University Health System from 2002 to 2015. FUBCs were defined as blood cultures performed from 24 hours to 7 days from initial positive blood culture. RESULTS: Among 1702 patients with GNB, 1164 (68%) had FUBCs performed. When performed, FUBCs were positive in 20% (228/1113) of cases. FUBC acquisition was associated with lower all-cause in-hospital mortality (108/538, 20%, vs. 176/1164, 15%; p 0.01) and attributable in-hospital mortality (78/538, 15%, vs. 98/1164, 8%; p < 0.0001). Propensity score-weighted Cox proportional hazards models revealed that obtaining FUBCs was associated with reductions in all-cause (hazard ratio (HR) 0.629; 95% confidence interval (CI), 0.511-0.772; p < 0.0001) and attributable mortality (HR 0.628; 95% CI, 0.480-0.820; p 0.0007). Positive FUBCs were associated with increased all-cause mortality (49/228, 21%, vs. 110/885, 11%; p 0.0005) and attributable mortality (27/228, 12%, vs. 61/885, 7%; p 0.01) relative to negative FUBCs. Propensity score-weighted Cox proportional hazards models revealed that positive FUBCs were associated with increased all-cause (HR 2.099; 95% CI, 1.567-2.811; p < 0.0001) and attributable mortality (HR 1.800; 95% CI, 1.245-2.603; p 0.002). In a calibration analysis, a scoring system accurately identified patients at high risk of positive FUBCs. CONCLUSIONS: Rates of positive FUBCs were high and identified patients at increased risk for mortality. Clinical variables can identify patients at high risk for positive FUBCs. FUBCs should be considered in the management of GNB.

[Sleep disorders: strategies for managing conflict by insomnia patients]. / Schlafstörungen: Konfliktbewältigungsstrategien von Insomniepatienten.

The investigation compares 136 insomniacs with 102 healthy controls with respect to their coping strategies. Coping strategies are evaluated with the questionnaire FKBS. This questionnaire measures 5 different coping strategies: TAS--turning against subject; TAO--turning against object; REV--reversal; PRN--prinzipialisation; PRO projection. Insomniacs seem to react less aggressive than healthy controls. They also show less projections, i.e. they do not believe in a hostile intention of a situation or a counterpart. These differences could be shown on the level of behaviour as well as experience. With the personality traits of the FPI (Freiburger Persönlichkeitsinventar FPI-R) there are some significant correlations. Finally there exists also a correlation between the strategy TAS and the incidence and intensity of depressive symptoms (i.e. state-variabels).

Pharmacology of fluperlapine compared with clozapine.

3-Fluoro-6-(4-methyl-piperazinyl)- 11H -dibenz [b,e]azepine ( fluperlapine , NB 106-689) resembles clozapine qualitatively and quantitatively in that it causes sedation, muscle relaxation, anticholinergic effects, no catalepsy, has little effect on apomorphine- and amphetamine-induced behaviour, does not induce apomorphine supersensitivity, and increases dozing and spindle activity in the rat's EEG. In the striatum of rats, it binds less to dopamine (DA) D2-receptor sites, but it enhances DA-turnover more than clozapine. Like clozapine and unlike haloperidol, it is equally active in the striatum, the nucl . accumbens and the cortex. Unlike clozapine, it does not significantly enhance norepinephrine (noradrenaline, NA)- or 5-hydroxytryptamine turnover and it does not increase prolactin blood levels significantly. Of the two compounds, only fluperlapine has some effects in common with antidepressants, i.e. tetrabenazine-antagonism and NA-uptake inhibition in slices of rat brain in vitro and ex vivo.

The pharmacology of 5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzothiadiazole (DS 103-282), a novel myotonolytic agent.

5-Chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzothiadiazole (DS 103-282) is a centrally acting agent with a novel chemical structure and a pharmacological profile different from that of myotonolytic drugs in current use such as diazepam, baclofen and dantrolene. It inhibits alpha- and gamma-rigidity in rats, reflex muscle tone in rabbits and the linguomandibular reflex in cats at low doses, but has little or no effect on gross spinal reflexes or electrically-induced segmental reflexes in cats. The mechanism underlying the muscle relaxation is unknown. Effects on convulsions induced by impaired GABA-transmission and by strychnine suggest a possible influence on glycine-mediated neurotransmission. In muscle-relaxing doses, DS 103-282 is without appreciable sedative, haemodynamic or neurochemical effects. Clinical investigations have confirmed the pharmacological predictions with regard to both the myotonolytic activity and the low propensity to produce side-effects.

[The course of blood pressure and organ changes in rats with DOCA-hypertension]. / Blutdruckverlauf und Organveränderungen bei Ratten mit DOCA-Hochdruck

In 45 control rats and 47 nephrectomized, DOCA-implanted, hypertensive rats (hypertensive phase), blood pressure, weight gain, development of pathologic-anatomical histological changes as well as changes in the myocardial enzyme pattern were studied over 24 weeks and after absorption of the DOCA tablet the return of the animals to normal conditions (follow-up phase) for another 14 weeks. During the hypertensive phase, blood pressure rose to 233 mm Hg on the average within 10 weeks and remained constant up to the 22nd week. In the follow-up phase, it dropped sharply, at first, and then slowly returned to normal. Weight gain was the same in DOCA and control rats. Relative weights of heart, kidneys and liver were elevated in the hypertensive phase but fell again in the follow-up phase. The pathologic-histological changes formed in the hypertensive phase, such as myocardial hypertrophy, glomerular hyalinization, tubular dilation and perivascular fibrosis, were remitted in part. Unchanged, however, the enhanced heart score persisted evidencing a proliferative vasoconstriction. Except for a pronounced, reversible increase in MAO activity, the cardial enzyme pattern remained unchanged during the experiment.

Pharmacological actions of the antihypertensive agent N-amidino-2-(2,6-dichlorophenyl)acetamide hydrochloride (BS 100-141).

Pharmacological properties characterizing N-amidino-2-(2,6-dichlorophenyl)acetamide hydrochloride (BS 100-141) as a centrally acting antihypertensive agent are described. Its action resembles that of clonidine in many respects but with important differences which are discussed. In DOCA-NaCl--hypertensive conscious rats, BS 100-141 lowers systemic blood pressure with oral doses of 0.3-5 mg/kg. Evidence for a central site of action is provided by the following findings. Infusion of BS 100-141 into the vertebral artery of anaesthetized dogs reduces blood pressure, the same dose being ineffective by i.v. route. Injection into the lateral cerebral ventricle of anaesthetized cats causes a marked reduction in blood pressure and heart rate, the same dose being ineffective when given i.v. The effects of intraventricular injection are inhibited by phentolamine administered by the same route. Intravenous administration of BS 100-141 induces dose-dependent reductions in the splanchnic (sympathetic) nerve activity in the cat. BS 100-141 reduces noradrenaline turnover in the brain stem of the rat as a result of central alpha-adrenoceptor stimulation. Doses which are effective in the hypertensive rat do not reduce dopamine turnover in the corpus striatum. The peripheral, direct alpha-sympathomimetic action of BS 100-141 was demonstrated by the transient increases in blood pressure observed in rats. These increases were unaffected by pretreatment with reserpine, but were antagonized by phentolamine. BS 100-141 was shown to induce contractions of isolated veins and arteries which were competitively inhibited by phentolamine. It stimulates presynaptic cardiac sympathetic alpha-adrenoceptors, thus inhibiting transmitter release to the heart. The sedative effects of BS 100-141 observed in dogs were slight compared to those of clonidine.

Clozapine and the dopamine hypothesis of schizophrenia, a critical appraisal.

This paper discusses some of the pharmacological and neurochemical properties of clozapine, and the special attributes that differentiate clozapine from the classical neuroleptics. The question as to whether or not clozapine blocks DA-receptors--a crucial point in regard to the dopamine hypothesis of schizophrenia--has received particular attention. Neurochemical, neuropharmacological, and endocrinological evidence is presented which speaks against a DA-receptor blockade by clozapine in pharmacologically relevant doses. These findings are difficult to reconcile with the dopamine hypothesis which proposes a direct relationship between antipsychotic effect and DA-receptor blockade.