Penetration of moxifloxacin into liver tissue

Moxifloxacin is considered for treatment of pyogenic liver abscesses as well as antibiotic prophylaxis in the case of hepatobiliary interventions. The aim of this study was to provide data on the pharmacokinetic (PK) profile of moxifloxacin in serum and liver tissue of patients undergoing liver resection due to primary or secondary tumours of the liver. Patients scheduled for liver resection (n=34) received moxifloxacin 400 mg at randomised time intervals prior to surgery. Blood and healthy liver tissue were sampled 1.5-26 h after administration of moxifloxacin. Immediately after centrifugation, plasma was separated, frozen and stored until analysis. In a subgroup of 19 patients, additional plasma specimens were obtained after 2, 4, 8, 12, 24, 36 and 48 h to assess the PK profile. PK parameters of moxifloxacin were calculated applying a two-compartment model. Median (interquartile range) PK parameters were as follows: peak concentration at the end of moxifloxacin infusion (C(max)), 6.0 mg/L (4.8-7.1 mg/L); area under the concentration-time curve extrapolated to infinity (AUC(0-∞)), 51.1 mgh/L (40.3-57.7 mgh/L); elimination half-life, 13.2h (11.0-14.1 h); volume of distribution at steady state (V(ss)), 138.7 L (102.7-168.5 L); and total body clearance (CL), 7.8 L/h (6.9-9.9L/h). Mean tissue concentrations were 9.13 mg/kg after 1.6-2.4 h, 7.62 mg/kg after 2.6-4.9h, 7.48 mg/kg after 5.6-10.0 h and 6.24 mg/kg after 22.9-26.5 h. Mean tissue:serum ratios were 2.9, 3.4, 5.0 and 12.3, respectively. The lowest tissue concentration found in the study at any time point was 2.8 mg/kg. In conclusion, moxifloxacin rapidly penetrates into the liver tissue where its concentration remains high following intravenous administration. Therefore, intravenously applied moxifloxacin might be used for the treatment of bacterial liver infections such as pyogenic liver abscess as well as in pre-operative prophylaxis.     

Axonal thinning and extensive remyelination without chronic demyelination in spinal injured rats

Remyelination following spinal cord injury (SCI) is thought to be incomplete; demyelination is reported to persist chronically and is proposed as a compelling therapeutic target. Yet most reports do not distinguish between the myelin status of intact axons and injury-severed axons whose proximal stumps persist but provide no meaningful function. We previously found full remyelination of spared, intact rubrospinal axons caudal to the lesion in chronic mouse SCI. However, the clinical concept of chronically demyelinated spared axons remains controversial. Since mouse models may have limitations in clinical translation, we asked whether the capacity for full remyelination is conserved in clinically relevant chronic rat SCI. We determined myelin status by examining paranodal protein distribution on anterogradely labeled, intact corticospinal and rubrospinal axons throughout the extent of the lesion. Demyelination was evident on proximal stumps of severed axons, but not on intact axons. For the first time, we demonstrate that a majority of intact axons exhibit remyelination (at least one abnormally short internode, <100 μm). Remarkably, shortened internodes were significantly concentrated at the lesion epicenter and individual axons were thinned by 23% compared with their rostral and caudal zones. Mathematical modeling predicted a 25% decrease in conduction velocity at the lesion epicenter due to short internodes and axonal thinning. In conclusion, we do not find a large chronically demyelinated population to target with remyelination therapies. Interventions may be better focused on correcting structural or molecular abnormalities of regenerated myelin.     

Camptocormia phenotype of FSHD: a clinical and MRI study on six patients

Recently it has been postulated that there is an atypical facioscapulohumeral muscular dystrophy (FSHD) phenotype with isolated axial myopathy. Involvement of paraspinal and limb muscles was evaluated in six patients with molecularly proven FSHD and a predominant bent spine phenotype. Consistent with the camptocormia phenotype, the most severely affected muscles in all six patients were the thoracic and lumbar spinal tract together with hamstrings. MRI disclosed severe axial muscle degeneration but mostly subclinical involvement of limb muscles. The involvement of hip extensor muscles in FSHD might considerably contribute to the clinical phenotype of camptocormia due to axial muscle involvement.     

Cerebellar hemorrhage in extremely low birth weight siblings: is there a familial disposition?

Cerebellar hemorrhage is an underrecognized complication in the preterm neonate. It is multifactorial including combined maternal, intrapartum, and early postnatal factors. We present the case of 2 preterm brothers, 24 + 1 and 24 + 3 weeks of gestation, who both died because of cerebellar hemorrhage. We sought familial pathogenic factors predisposing to cerebellar hemorrhage. Cerebral imaging performed by ultrasonography through the anterior fontanel was normal and showed no signs of bleeding or brain edema. Postmortem neuropathologic findings confirmed cerebellar hemorrhagic lesions in both infants. Cerebellar vessels showed no signs of morphologic disorders or malformations. There might be a hint to a familial disposition. Neonatal cranial ultrasound protocols should include brainstem and posterior fossa examination with specific scans through the mastoid fontanel.     

A population-based study of associations between current posttraumatic stress symptoms and current fatigue

This study explores current experience with posttraumatic stress disorder (PTSD) symptoms and other variables (sociodemographic, mental distress, somatic morbidity, self-rated health, and quality of life [QoL]) in relation to fatigue. A representative sample of the Norwegian population (N = 3,944) was invited to participate in a mailed survey, and 1,857 (47%) returned valid responses on the questionnaire that included the Fatigue Severity Scale and the Posttraumatic Symptom Scale-10. Posttraumatic stress disorder symptoms showed a strong association with fatigue in univariate (β = .41) and multivariate analyses (β = .33). Associations between psychosocial health variables, QoL, and fatigue were confirmed. However, PTSD symptoms showed the strongest association with fatigue in the analyses. Findings need to be replicated in other population samples and in clinical samples with PTSD and fatigue.     

The other side of the coin: perceived positive effects of illness in women following acute myocardial infarction.

BACKGROUND: Although myocardial infarction (MI) is linked with both physical and psychological impairments, the possibility of patients also experiencing positive outcomes of MI has received far less attention in research and in clinical practice. In particular, this aspect has been under-investigated in older persons and in women. AIM: The purpose of this study was to investigate possible positive effects of illness, describe the patient characteristics and explore the nature and frequency of these effects in older women after MI. METHODS: A cross-sectional postal survey was conducted in 145 women aged 62-80 years, three months to five years after MI. Self-reported socio-demographic and clinical data, in addition to data from medical records, were collected. A single-item question--"All in all, was there anything positive about experiencing an MI?"--was used to assess positive effects of illness, in addition to an open-ended question on the nature of possible positive effects. RESULTS: A majority of the women (65%) reported positive effects from their MI experience. The women perceiving positive effects did not differ from those who did not on socio-demographic and clinical variables, except for being older (p=0.007) and less often readmitted (p=0.029). The groups did not differ significantly as to disease severity and time since MI. Four themes emerged from the open-ended questioning on the nature of perceived positive effects of the illness: Appreciating Life (55%), Getting Health Care (42%), Making Lifestyle Changes (36%), and Taking More Care of Self and Others (29%). CONCLUSIONS: The findings contribute to a more complete picture of psychosocial issues in women after MI by providing evidence that positive effects are often experienced despite physical limitations. Nurses may use this knowledge as a tool in patient education and communication, although further research is needed to determine the most optimal interventions for MI patients.