Arterial stenosis in antiphospholipid syndrome: Update on the unrevealed mechanisms of an endothelial disease

First described in 1983, antiphospholipid syndrome (APS) is an autoimmune condition characterized by the occurrence of recurrent arterial and/or venous thrombosis, and/or pregnancy morbidity, in the setting of persistent presence of antiphospholipid antibodies (aPL). While thrombosis is the most well-known pathogenic mechanism in this disorder, the relevance of some other mechanisms such as arterial stenosis is being increasingly recognized. Arterial stenosis has been first described in the renal arteries in patients with APS, however intracranial and coeliac arteries can also be involved with various and treatable clinical manifestations. The underlying pathophysiology of this stenotic arterial vasculopathy is not fully understood but some recent studies revealed new insights into the molecular mechanism behind this endothelial cell activation in APS. In this review, we discuss these newly discovered mechanisms and highlight the diagnostic and therapeutic modalities of the APS related arterial stenosis.     

The treatment of antiphospholipid syndrome: a harmonic contrast

The antiphospholipid syndrome (APS) is characterized by a wide variability in clinical manifestations. Recommendations for therapy are conditioned by the lack of appropriate studies, due either to methodological limitations or excessive selection of patients. There is consensus in treating patients with APS and first venous thrombosis with warfarin to a target international normalized ratio (INR) of 2.3-3.0. However, a recent systematic review including observational studies found patients with APS and stroke to be at a high risk of recurrent events. We thus recommend a target INR>3.0 in this group. Likewise, the optimal approach for women with obstetric manifestations of APS is not completely defined; some authors recommend universal aspirin plus heparin whereas others consider aspirin in monotherapy useful for women with recurrent early miscarriage only. Correction of vascular risk factors and a high-risk management of pregnancy, including Doppler studies of the uterine and umbilical vessels, are warranted. Hydroxychloroquine and statins are likely to become important in the future.     

Partial volume tolerance of the spinal cord and complications of single-dose radiosurgery

BACKGROUND: Spine radiosurgery causes a rapid dose fall-off within the spinal cord. The tolerance of partial volume of the spinal cord may determine the extent of clinical application. The study analyzed the partial volume tolerance of the human spinal cord to single fraction radiosurgery. METHODS: A total of 230 lesions with spine metastases in 177 patients were treated with radiosurgery with single fraction of 8 to 18 Gy, prescribed to the 90% isodose line that encompassed the target volume. Spinal cord volume was defined as 6 mm above and below the radiosurgery target volume. Spinal cord dose was calculated from the radiation dose/spinal cord volume histogram and correlated with clinical/neurological status and radiographic studies. Median follow-up was 6.4 months (range, 0.5-49 months). The 1-year survival rate was 49%. RESULTS: The average spinal cord volume defined at the treated spinal segment was 5.9 +/- 2.2 mL. The average dose to the 10% spinal cord volume was 9.8 +/- 1.5 Gy, calculated from the dose-volume histogram in the group of 18 Gy prescribed dose. The spinal cord volume that received higher than 80% of the prescribed dose was 0.07 +/- 0.10 mL, which represented 1.3 +/- 1.8% of the cord volume. Among the 86 patients who survived longer than 1 year there was 1 case of radiation-induced cord injury after 13 months of radiosurgery. There were no other cases of spinal cord sequelae. CONCLUSIONS: Whereas the maximum spinal cord tolerance to single-dose radiation is not known, partial volume tolerance of the human spinal cord is at least 10 Gy to 10% of the spinal cord volume defined as 6 mm above and below the radiosurgery target.     

Combined Radiofrequency Ablation-Cooling Catheter for Reversible Cryothermal Mapping and Ablation

Reversible cryothermal mapping of cardiac arrhythmias has beenperformed intraoperatively. However, a steerable cooling catheter forreversible mapping has not yet been developed. We therefore developed andtested a cooling system consisting of a +15°C hypertonic salinereservoir and a 7F steerable catheter also capable of radiofrequency (RF)ablation. Using excised ovine hearts placed in a 37°C circulating salinebath, we measured the temperatures at depths of 0 mm, 1 mm, and 2 mm. Thetemperature after 90 seconds of cooling was 16.5 ± 2.1°C at 0 mmcompared to 23.9 ± 4.1°C at 1 mm and 31.1 ± 3.9°C at 2mm depth (p < 0.01). These data suggest that a 7F steerable combined RFablation–cooling catheter may achieve temperatures suitable formapping arrhythmias such as atrial tachycardias and right ventricularoutflow tract tachycardias. Further enhancements to achieve lowertemperatures at depth may be needed to reversibly map other arrhythmiassuch as left ventricular tachycardias.     

Clinical, Endoscopic, Immunologic, and Therapeutic Aspects of Oropharyngeal and Esophageal Candidiasis in HIV-Infected Patients: A Survey of 114 Cases

The medical records of 114 consecutive HIV-infected patients with oropharyngeal and esophageal candidiasis, in whom esophagoscopy was performed, were reviewed. Esophageal candidiasis and isolated oral candidiasis were found in 75% and 25% of patients, respectively. Esophageal candidiasis was the AIDS-defining illness in 65 patients and dysphagia was the commonest symptom, but asymptomatic Candida esophagitis was observed in 43% of them. Symptoms were present in six patients with oropharyngeal candidiasis; three of them had a normal esophagoscopy and the other three had acute nonfungal esophagitis. Invasive fungal esophagitis was confirmed by biopsy in 47/74 patients (64%). The patients with esophageal candidiasis had lower CD4+ cell counts (129/microliter) and CD4:CD8 ratios (0.23) than those with oropharyngeal candidiasis (CD4 179/microliter; CD4:CD8 0.35). Thirty-six patients with esophageal candidiasis were treated with fluconazole, 100 mg/daily, for 28 days, and another 34 patients received the same dose for 10 days. A similar efficacy was seen in both regimens, but a higher incidence of oropharyngeal fungal colonization and liver dysfunction was observed in the longer therapy (p < 0.001). We conclude that asymptomatic C. esophagitis is common in HIV-infected patients. Patients with oropharyngeal candidiasis may complain of esophageal symptoms; it could be due to superficial C. infection or another not-identified opportunistic infection. More severe immunologic impairment was required to develop esophageal candidiasis than oropharyngeal candidiasis. A short course of 10 days of fluconazole therapy could be the standard regimen for the treatment of C. esophagitis in AIDS.     

Anti-52 kDa Ro, anti-60 kDa Ro, and anti-La antibody profiles in neonatal lupus

OBJECTIVE: Studies suggest that anti-52 kDa Ro antibodies are more sensitive and specific than anti-60 kDa Ro antibodies for neonatal lupus. However, these studies mainly used immunoblot or ELISA using recombinant protein, which have poor sensitivity for anti-60 kDa Ro antibodies. In addition, the control patients were not disease matched. We reassessed the sensitivity and specificity of anti-52 kDa Ro, anti-60 kDa Ro, and anti-La, addressing these limitations. METHODS AND RESULTS: To assess sensitivity, 125 mothers of children with neonatal lupus (NLM) were recruited. All maternal sera were assessed using a commercial line immunoassay that uses natural 60 kDa Ro protein (Inno-Lia ANA Update, Innogenetics NV, Gent, Belgium). By this method, 96% of the sera had antibodies to 60 kDa Ro, 86% to 52 kDa Ro, and 78% to 48 kDa La. Immunoblot of 65 NLM showed significantly fewer positive results for anti-60 kDa Ro (p < 0.001) and anti-52 kDa Ro (p < 0.05). Sensitivity of the 3 antibodies was assessed in the symptomatic mothers of children with congenital heart block (CHB) (78 women) and disease matched controls with unaffected children (65 women) using Inno-Lia ANA Update. The sensitivity of each antibody was compared by multiple logistic regression to adjust for maternal disease. There was no significant difference between the groups for 60 kDa Ro or for anti-52 kDa Ro antibody. However, there was a significant difference for the anti-La antibody (p = 0.001), with an odds ratio of 3.59. This translates to an increase in risk from a published 2% for CHB in an anti-Ro-positive mother to 3.1% if the woman is also anti-La antibody-positive, and to a decrease in risk to 0.9% if anti-La-negative. CONCLUSION: Contrary to previous reports, 52 kDa Ro as detected by Inno-Lia ANA Update is not more specific for or frequent in CHB than 60 kDa Ro. However, the presence of anti-La antibodies significantly increases the risk for CHB.     

Modulation of segmental mechanisms by activation of a dorsal column brainstem spinal loop

In decerebrate-decerebellate cats, dorsal column stimulation (DCst) rostral to selective dorsal funicular cuts, to prevent antidromic activation of afferent DC fibers, produced primary afferent depolarization and modulated reflexes at the lower spinal level. These findings indicate the importance of a DC-brainstem-spinal loop in explaining the effects of DC stimulation in man and experimental animals.