p38 MAPK signaling acts upstream of LIF-dependent neuroprotection during photoreceptor degeneration.

In many blinding diseases of the retina, loss of function and thus severe visual impairment results from apoptotic cell death of damaged photoreceptors. In an attempt to survive, injured photoreceptors generate survival signals to induce intercellular protective mechanisms that eventually may rescue photoreceptors from entering an apoptotic death pathway. One such endogenous survival pathway is controlled by leukemia inhibitory factor (LIF), which is produced by a subset of Muller glia cells in response to photoreceptor injury. In the absence of LIF, survival components are not activated and photoreceptor degeneration is accelerated. Although LIF is a crucial factor for photoreceptor survival, the detailed mechanism of its induction in the retina has not been elucidated. Here, we show that administration of tumor necrosis factor-alpha (TNF) was sufficient to fully upregulate Lif expression in Muller cells in vitro and the retina in vivo. Increased Lif expression depended on p38 mitogen-activated protein kinase (MAPK) since inhibition of its activity abolished Lif expression in vitro and in vivo. Inhibition of p38 MAPK activity reduced the Lif expression also in the model of light-induced retinal degeneration and resulted in increased cell death in the light-exposed retina. Thus, expression of Lif in the injured retina and activation of the endogenous survival pathway involve signaling through p38 MAPK.

[Atrioventricular heart block in Lyme disease]. / Bloc atrioventriculaire complet sur borréliose de Lyme: aspects etectrocardiographiques, diagnostiques et microbiologiques.

Lyme disease is the most common tick-borne disease in Europe and in the United States. In comparison to dermatological, neurological and rheumatological manifestations, heart disease is quite rare. Atrioventricular heart block is nevertheless the most frequent cardiological manifestation. We hereby report the case of a patient with high degree heart block due to Lyme disease. We focus on the electrocardiographical evolution during antibiotic therapy, as well as on microbiological and diagnostic aspects. Lyme disease is a rare cause of conduction disturbances but it is treatable and potentially reversible.

Beating heart coronary artery surgery: is sternotomy a suitable alternative to minimal invasive technique?

OBJECTIVES: To evidence the respective advantages and drawbacks of minimal invasive-thoracotomy (MIDCAB) and off-pump sternotomy (OPCAB) coronary bypass techniques. METHODS: The perioperative and mid-term (3 months) results of the first 31 MIDCABs and 39 OPCABs performed by a single experienced coronary surgeon (F.S.) were compared. Differences were assessed by two-tailed chi-square or unpaired t-test, and significance assumed for P-values < or =0.05. RESULTS: Groups were widely comparable. There were no in-hospital deaths nor permanent neurologic events. OPCAB patients received more anastomoses (mean 1.09/patient vs. 1.89/patient, P<0.001) during a shorter coronary occlusion period (26.1+/-8 vs. 16.6+/-4.5min, P<0.001), whilst immediate extubation prevailed in MIDCABs (22/31 vs. 17/39, P<0.05). Significant complications occurred in seven MIDCABs vs. none in OPCABs (P<0.01). Other in-hospital parameters were similar. Controls at 3 months evidenced more residual discomfort among MIDCAB patients (14/30 vs. 7/39, P<0.05). CONCLUSIONS: Differences in early complication rates may be due to a learning effect. However, OPCAB allows us to implant more grafts and is more comfortable for both patient and surgeon. These advantages may well counterbalance the cosmetic benefits of MIDCAB procedures.

Photoreceptor autophagy: effects of light history on number and opsin content of degradative vacuoles.

PURPOSE: To investigate whether regulation of rhodopsin levels as a response to changed lighting environment is performed by autophagic degradation of opsin in rod inner segments (RISs). METHODS: Groups of albino rats were kept in 3 lux or 200 lux. At 10 weeks of age, one group was transferred from 3 lux to 200 lux, another group was switched from 200 lux to 3 lux, and two groups remained in their native lighting (baselines). Rats were killed at days 1, 2, and 3 after switching. Another group was switched from 3 lux to 200 lux, and rats were killed at short intervals after the switch. Numbers of autophagic vacuoles (AVs) in RISs were counted, and immunogold labeling was performed for opsin and ubiquitin in electron microscopic sections. RESULTS: The number of AVs increased significantly after switching from 3 lux to 200 lux at days 1 and 2 and declined at day 3, whereas the reverse intensity change did not cause any increase. Early time points after change from 3 lux to 200 lux showed a significant increase of AVs 2 and 3 hours after switching. Distinct opsin label was observed in AVs of rats switched to 200 lux. Ubiquitin label was present in all investigated specimens and was also seen in AVs especially in 200-lux immigrants. CONCLUSIONS: Earlier studies had shown that an adjustment to new lighting environment is performed by changes in rhodopsin levels in ROSs. Autophagic degradation of opsin or rhodopsin may subserve, at least in part, the adaptation to abruptly increased habitat illuminance by removing surplus visual pigment.

Image quality and dose in spiral computed tomography.

Image quality and dose produced by a spiral CT with various pitch values were investigated on the basis of test-object images and measurements of CT dose indexes. No major difference in image quality or dose was observed when comparing sequential and spiral mode acquisition with a pitch of one. Increase in pitch value produces a loss of contrast which leads to a loss of detectability. Nevertheless, in realistic protocols the image quality in the transverse plane remains acceptable up to pitch values of 1.3-1.6.

Regulation of inspiratory neuromuscular output during synchronized intermittent mechanical ventilation.

BACKGROUND: In synchronized intermittent mandatory ventilation, it is generally accepted that the work of the inspiratory muscles is decreased by the ventilator so that their activity can be modulated by the frequency of assisted breaths. We examined the validity of this concept, which recently has been questioned. METHODS: We studied five patients receiving synchronized intermittent mandatory ventilation because of an acute exacerbation of chronic obstructive pulmonary disease. The level of machine assistance, defined as the percentage of total ventilation delivered by the ventilator, was varied from a high (> 60%) to a medium (20-50%) and to the lowest tolerated value (0% in four patients). Esophageal pressure, air flow, and the electromyograms of the diaphragm and sternocleidomastoid muscles were recorded. At each level of machine assistance, distinguishing assisted from spontaneous breaths, the duration of electrical activation, the integrated electromyograms, and the work of breathing were computed. RESULTS: The durations of electrical activation and the integrated electromyograms of the diaphragm and sternocleidomastoid were similar in successive spontaneous and assisted breaths. At > 60% of machine assistance, the cumulative values per minute of the integrated electromyograms of the diaphragm and sternocleidomastoid and the work of breathing were reduced only by 38, 32, and 44%, respectively, compared with the lowest tolerated level of machine assistance. The durations of electrical activation did not change with increasing level of machine assistance. CONCLUSIONS: The degree of inspiratory muscle rest achieved by synchronized intermittent mandatory ventilation is not proportional to the level of machine assistance; furthermore, the inspiratory motor output is not regulated breath by breath but rather is constant for a given level of machine assistance.