Novel Rodent Models for Macular Research

BACKGROUND: Many disabling human retinal disorders involve the central retina, particularly the macula. However, the commonly used rodent models in research, mouse and rat, do not possess a macula. The purpose of this study was to identify small laboratory rodents with a significant central region as potential new models for macular research. METHODOLOGY/PRINCIPAL FINDINGS: Gerbillus perpallidus, Meriones unguiculatus and Phodopus campbelli, laboratory rodents less commonly used in retinal research, were subjected to confocal scanning laser ophthalmoscopy (cSLO), fluorescein and indocyanine green angiography, and spectral-domain optical coherence tomography (SD-OCT) using standard equipment (Heidelberg Engineering HRA1 and Spectralis™) adapted to small rodent eyes. The existence of a visual streak-like pattern was assessed on the basis of vascular topography, retinal thickness, and the topography of retinal ganglion cells and cone photoreceptors. All three species examined showed evidence of a significant horizontal streak-like specialization. cSLO angiography and retinal wholemounts revealed that superficial retinal blood vessels typically ramify and narrow into a sparse capillary net at the border of the respective area located dorsal to the optic nerve. Similar to the macular region, there was an absence of larger blood vessels in the streak region. Furthermore, the thickness of the photoreceptor layer and the population density of neurons in the ganglion cell layer were markedly increased in the visual streak region. CONCLUSIONS/SIGNIFICANCE: The retinal specializations of Gerbillus perpallidus, Meriones unguiculatus and Phodopus campbelli resemble features of the primate macula. Hence, the rodents reported here may serve to study aspects of macular development and diseases like age-related macular degeneration and diabetic macular edema, and the preclinical assessment of therapeutic strategies

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

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

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

Activation of survival pathways in the degenerating retina of rd10 mice

Blinding diseases of the retina are frequently characterized by loss of photoreceptor cells. The retinal degeneration 10 (rd10) mouse expresses a mutant form of rod phosphodiesterase leading to autosomal recessive photoreceptor degeneration. In contrast to rd1, rd10 mice have remaining rod function mimicking more closely most forms of human Retinitis Pigmentosa. Here we use morphology, biochemistry, retinal whole mounts, real-time PCR, Western blotting and immunofluorescence to compile a comprehensive report on progression of retinal degeneration in the rd10 retina up to one year of age. We show that retinal development, morphology, gene expression pattern and retinal vasculature was normal until postnatal day 15. Thereafter, a bi-phasic pattern of rod cell death emerged with a first rapid phase peaking around 3 weeks of age followed by a slower second phase. Death of cone cells followed with a delay and vessel dropout was prominent in the retinal periphery of 6 months old rd10 mice. At one year of age, RPE atrophy was evident. The degenerating retina rapidly induced expression of transcriptional regulators Atf3 and Cebpd. Induction of Atf3 was transient and lasted only for several days at the beginning of degeneration whereas levels of Cebpd remained elevated throughout the period of photoreceptor loss. Several protective genes such as Lif, Edn2 and Fgf2 which are implicated in a potent endogenous survival pathway, and Mt1 and Mt2 were strongly upregulated in the rd10 retina. In addition, increased expression of Casp1 and Il1b suggested an inflammatory response

Repeated β irradiation for failed intracoronary radiation therapy in patients with in-stent restenosis

Vascular brachytherapy (VBT) is the only proven treatment option for patients with in-stent restenosis. In seven randomised trials with almost 1500 patients that evaluated {gamma} (five studies) and ß (two trials) irradiation, target vessel failure reduction ranged from 73% to 34% by VBT compared with conventional angioplasty.1 However, the reported restenosis rates with the active treatment still varied between 17% and 32%.1 We therefore postulated that repeat VBT is safe and efficacious for preventing refractory in-stent restenosis in high risk patients with failed VBT. METHODS Beginning in January 1999, VBT was applied for all patients with in-stent restenosis. VBT was systematically performed with intravascular ultrasound (IVUS) guidance. The repeat procedure was performed with a strontium/yttrium-90 source train (BetaCath, Novoste, Norcross, Georgia, USA). The design and application of this catheter have been described previously.2 The dosimetry was based on the manufacturer’s recommendations but taking into account not the angiographic vessel reference diameter but the external elastic membrane diameter (as determined by IVUS). The mean dose delivered at 2 mm from the source centre was 23.3 (2.2) Gy during the index procedure and 25.3 (2.2) Gy during the repeat intervention. Percutaneous coronary intervention (PCI) was performed according to standard clinical practice. Failed VBT was defined as angina recurrence combined with target vessel failure (as documented by any repeat angiography: premature depending on early symptom recurrence or at the planned six month control). Repeat VBT was considered for patients estimated to be at high risk for refractory in-stent restenosis or if they had a prognostic risk—that is, diffuse or ostial in-stent restenosis or total occlusion, or proximal left anterior descending artery stenosis. Focal edge effect stenoses and non-prognostic lesion locations in symptomatic patients were treated by conventional PCI. Written informed consent was obtained from all patients before intervention. The study was approved by the hospital ethics committee. All VBT patients were prospectively entered in a dedicated database by a person not taking part in the interventions. A combined antiplatelet treatment (aspirin 100 mg and clopidogrel 75 mg daily) was prescribed for at least six months after the index procedure and for one year after the second VBT. Control angiography was mandatory at six months in all VBT patients and systematic long term clinical follow up was carried out. RESULTS Between July 1998 and March 2003, 251 VBT interventions were performed at our institution: 22 patients were treated for primary restenosis prevention and 229 patients for in-stent restenosis. VBT failed in 34 patients (14.8%): 23 underwent conventional PCI and 11 underwent repeat VBT. The baseline clinical and angiographic demographics were comparable for both groups. Concerning the repeat VBT group, mean (SD) age was 60 (7) years, nine patients were men, and two had diabetes. All patients who underwent a repeat procedure had incapacitating angina pectoris. Angina recurred at 7 (2) months (range 4–10) after the first, failed VBT. The restenosis pattern (table 1Go) was diffuse in the majority of patients at the first presentation and remained diffuse with exacerbation to total occlusion in two patients. In the focal restenosis group, two patients had ostial in-stent restenosis. The cause of recurrent in-stent restenosis was an evident geographical miss in two patients (a focal and a diffuse pattern case). IVUS and angioplasty were successful before irradiation therapy in all patients. During repeat VBT, a 40 mm source train was used in seven patients and a pullback technique was required in two because of the length of the restenotic segment. No additional stents were implanted and no evidence of geographical miss was seen at repeat intervention. Table 1Go shows quantitative coronary angiography and IVUS data. During the index procedure, the minimum in-stent luminal area increased from mean (SD) 5.8 (1.8) to 7.5 (1.4) mm2. This area was maintained at the repeat intervention at 7.8 (2.1) mm2 and further expanded to 8.9 (1.8) mm2. All repeat interventions were technically successful and there were no adverse clinical events during the in-hospital phase

Elective ostial left main stenting: a tailored approach

Elective left main (LM) stenting is increasingly performed as a valuable alternative to coronary artery bypass grafting. Nevertheless, clinical data are limited to registries, and randomized trials have not been published. Intravascular ultrasound (IVUS) has been recognized as an accurate tool for assessing optimal stent deployment. We hereby report the usefulness of IVUS in defining the interventional strategy in four consecutive patients presenting with severe, symptomatic ostial LM disease, and this in the era of drug-eluting stents. The first two patients were treated by a short drug-eluting stent for a critical LM stenosis as IVUS demonstrated a reference diameter < 3.7 mm. The third patient had a larger reference diameter and was treated with conventional stenting with optimization of the result by IVUS. IVUS was particularly helpful in all patients to confirm accurate stent placement in relation to the LM ostium and bifurcation. In another patient, based on IVUS findings, surgery was preferred. This patient with diabetes as a risk factor presented with comparable angiographic features. IVUS, however, showed diffuse disease without any healthy reference segment in the LM. All stented patients are asymptomatic at 15 +/- 7 months follow-up with negative stress testing. The present observation indicates that IVUS is an essential tool for strategic selection and to optimize percutaneous coronary intervention for LM disease

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