Pathologic laughter and crying in ALS: a search for their origin

Spells of laughter and crying are well known in patients with amyotrophic lateral sclerosis (ALS). Since ALS occurs mostly in older age groups, this brings up the possibility that aging changes in the brain could play a causative role in the origin of such spells. To rule out or at least reduce the complicating factor of aging, a study was made of the incidence of pathologic laughter and crying in patients whose motor neuron disease had started before the age of 45 years. The data were collected from 73 such individuals, all with confirmed ALS. All told, 36 had experienced episodes of pathologic laughter and/or crying. Of these, 20 had bouts of both laughter and crying. 9 bouts of crying alone and 7 spells of laughter alone. Nearly all with such emotional spells had developed bulbar involvement with the illness. The youngest patient with spells was 31 when his illness began and 35 when he started to have bouts of crying.     

Delayed pain response after lumbar discography

Summary The delayed onset of symptomatic pain following lumbar discography (with no immediate pain response) is described in six patients, five with a minimum 2-year follow-up. It is usually seen in patients with nearly normal disc morphology who have incomplete or discrete annular tears that are not filled at the time of injection. Later (2–12 h in this study), dye leakage occurs through these lesions, thereby precipitating the discogenic pain This phenomenon may be missed and is probably more common than previously believed due to early discharge from the hospital, the patient expecting discomfort after the invasive study (hence no complaint is made), and the clinician being unaware of this delayed symptom, thereby not asking about it in follow-up. Close patient questioning regarding a delayed onset of symptomatic pain after discography is, therefore, an essential element in diagnostic information following this study.     

Trehalose protects against ocular surface disorders in experimental murine dry eye through suppression of apoptosis

The disaccharide trehalose is a key element involved in anhydrobiosis (the capability of surviving almost complete dehydration) in many organisms. Its presence also confers resistance to desiccation and high osmolarity in bacterial and human cells by protecting proteins and membranes from denaturation. The present study used a novel murine dry eye model induced by controlled low-humidity air velocity to determine whether topically applied trehalose could heal ocular surface epithelial disorders caused by ocular surface desiccation. In addition, the efficacy of 87.6 mM trehalose eyedrops was compared with that of 20% serum, the efficacy of which has been well documented. Mice ocular surface epithelial disorders were induced by exposure of murine eyes to continuous controlled low-humidity air velocity in an intelligently controlled environmental system (ICES) for 21 days, which accelerated the tear evaporation. The mice were then randomized into three groups: the control group received PBS (0.01M) treatment; a second group received 87.6 mM trehalose eyedrops treatment; and the third group received mice serum eyedrops treatment. Each treatment was administered as a 10 μl dose every 6 h for 14 days. The resultant changes in corneal barrier function and histopathologic examination of cornea and conjunctiva were analyzed and the level of apoptosis on the ocular surface was assessed using active caspase-3. After 14 days of treatment, the corneal fluorescein staining area, the ruffling and desquamating cells on the apical corneal epithelium, as well as the apoptotic cells on ocular surface epithelium had significantly reduced in eyes treated with trehalose compared with those treated with serum and PBS. In contrast, after 14 days of treatment, improvements in the thickness of the corneal epithelium, the squamous metaplasia in conjunctival epithelium and the number of goblet cells of the conjunctiva were less marked in eyes treated with trehalose compared with serum. These results demonstrated that trehalose could improve the appearance of ocular surface epithelial disorders due to desiccation through suppression of apoptosis. Trehalose produces some of the same responses as serum upon topical application and can maintain corneal health.     

Intimal hyperplasia and hemodynamic factors in arterial bypass and arteriovenous grafts: a review

Stenosis at the graft–vein junction caused by intimal hyperplasia (IH) is the major cause of failure of vascular access grafts used for hemodialysis. There is a strong relationship between hemodynamic factors and formation of IH. The hemodynamic pattern and the location of IH are different in arterial bypass grafts (ABGs) compared with arteriovenous grafts (AVGs). In an ABG, end-to-side anastomosis of the expanded polytetrafluoroethylene graft and artery produces hemodynamic changes around the junction. IH develops at the arterial floor and the toe and heel of the distal anastomosis. Low shear stress and oscillating shear forces at the arterial floor and the heel plus a high wall sheer stress (WSS) gradient at the toe probably promote IH development. Compliance mismatch between the graft and artery causes turbulence that may contribute to IH formation. The blood flow rate in AVGs is 5–10 times greater than that in ABGs. High flow causes turbulence that injures endothelial cells and eventually results in IH. The peak WSS in AVGs is about 6N/m², much higher than that in ABGs. Excessively high WSS may effect IH formation in AVGs. Several venous cuff or patch anastomotic designs have been used in attempts to regulate hemodynamic factors in grafts. In ABGs, these designs appear to help decrease IH formation. In AVGs, however, they generally have not improved patency rates. In a high-flow system such as an AVG, more drastic changes in anastomotic design may be required.     

Eosinophil cationic protein in tears of normal subjects and patients affected by vernal keratoconjunctivitis

The objectives of this study were to determine: 1) levels of tear eosinophil cationic protein (ECP) in patients with vernal keratoconjunctivitis (VKC); 2) the effect of pharmacologic therapy on ECP release; and 3) the correlation of this mediator with the severity of the disease. Tears were collected from 10 controls and 20 VKC patients before and after therapy for cytologic analysis and ECP measurement by radioimmunoassay. Ocular signs and symptoms were evaluated before tear collection. Mean ECP levels in controls were 7.5 ± 0.4 μg/l, and in VKC patients, 988.3 ± 128 μg/l before therapy ( P <0.001) and 566.3 ± 121 μg/l after therapy ( P <0.005). In dexamethasone (Dex) 0.1%, or cyclosporin A (CsA) 2%, patients (five per group), tear ECP decreased significantly after 7–14 days of treatment. Disodium cromoglycate (DSCG) 4% (five patients) for 14 days did not significantly affect ECP levels. ECP levels were significantly correlated with allergic signs ( P <0.001), symptoms ( P <0.001), and the number of eosinophils in tears (P<0.005). The results of this study suggest that tear ECP levels accurately reflect the clinical status of VKC patients. The measurement of ECP may prove useful not only in the diagnosis and monitoring of allergic disease, but also as an objective parameter for the evaluation of new antiallergic therapies.     

Fluid and solid mechanical implications of vascular stenting

Vascular stents have emerged as an effective treatment for occlusive vascular disease. Despite their success and widespread use, outcomes for patients receiving stents are still hampered by thrombosis and restensosis. As arteries attempt to adapt to the mechanical changes created by stents, they may in fact create a new flow-limiting situation similar to that which they were intended to correct. In vitro fluid mechanics and solid mechanics studies of stented vessels have revealed important information about how stents alter the mechanical environment in the arteries into which they are placed. Adverse nonlaminar flow patterns have been demonstrated as well as remarkably high stress concentrations in the vessel wall. In vivo studies of stented vessels have also shown a strong relationship between stent design and their dynamic performance within arteries. Alterations in pressure and flow pulses distal to the stent have been observed, as well as regional changes in vascular compliance. Considering the influence of flow and stress on the vascular response and the suboptimal clinical outcomes associated with stenting, knowledge gained from stent/artery mechanics studies should play an increasingly important role in improving the long-term patency of these devices. © 2002 Biomedical Engineering Society. PAC2002: 8719Rr, 8780-y, 8719Uv     

Long-term inhibition of intimal hyperplasia using vascular photodynamic therapy in balloon-injured carotid arteries

Flexible treatments for intimal hyperplasia after angioplasty are still needed. The aim of this study was to demonstrate the long-term effects of vascular photodynamic therapy with talaporfin sodium on intimal hyperplasia following interventional injury. Intimal hyperplasia was induced by balloon distension injury to the carotid artery in 31 rabbits. Talaporfin, 5.0 mg/kg, was delivered systemically immediately after balloon injury. The injury site was irradiated with a diode laser light of wavelength 664 nm using a fluence of 50 J/cm² after 30 min. At day 3 and weeks 3, 6, 9, 15, and 25 after photodynamic therapy, the treated artery of each rabbit was excised and examined immunohistochemically. Thirty minutes after talaporfin administration, drug fluorescence was found only in the balloon-injured carotid artery wall. At 3 days, no smooth muscle cells were seen in the media of the photodynamic therapy-treated arterial segments. Intimal hyperplasia developed progressively in the balloon-injured and untreated segments; however, in the segments treated with photodynamic therapy, intimal hyperplasia was markedly suppressed until 25 weeks and the media was repopulated by smooth muscle cells without macrophages. Vascular photodynamic therapy with talaporfin may be used to inhibit restenosis after vascular intervention. An erratum to this article is available at .