Advanced magnetic resonance imaging in benign hereditary chorea: Study of two familial cases

No brain abnormalities are usually detected on conventional magnetic resonance imaging (MRI) in benign hereditary chorea (BHC); there are currently no studies with advanced techniques in literature. We investigated whether conventional and advanced MRI techniques could depict regional brain abnormalities in two familial BHC patients and 24 healthy controls. No brain abnormalities on conventional scans were detectable; also, no significant differences in fractional anisotropy of the basal nuclei were observed. Volumetric analysis showed a decreased volume of the striatum bilaterally compared with controls, whereas spectroscopy demonstrated a significant increased myoinositol/creatine ratio bilaterally, a reduction of choline/creatine ratio bilaterally, and of N‐acetyl‐aspartate/creatine in the right putamen. With the limits of the small sample size in the patient group, these data show that, despite the absence of macroscopic changes on conventional MRI, volumetric and metabolic abnormalities are present in the basal nuclei of BHC patients. © 2010 Movement Disorder Society.     

Acute surgical removal of low-grade (Spetzler-Martin I-II) bleeding arteriovenous malformations

Background

Early surgical removal of cerebral AVMs is a relatively infrequent therapeutic option when dealing with a cerebral hemorrhage caused by AVM rupture: even in the case of low-grade AVMs, delayed treatment is, if possible, preferred because it is considered safer for patients and more comfortable for surgeons. To assess whether acute surgery may be a safe and effective management, we conducted a retrospective analysis of our early surgery strategy for ruptured low-grade AVMs.

Methods

We reviewed 27 patients with SM grade I-II AVM treated during 2004 to 2008 in the acute stage of bleeding (within the first 6 days after bleed). All patients showed a cerebral AVM on DSA at admission, and surgical removal was controlled by postoperative angiography. Neurological outcomes were assessed with GOS. The average length of follow-up was 22 months (48-3 months).

Results

Before surgery, 16 (59%) patients showed a GCS of 8 or less, 2 of them presenting an acute rebleeding after first hemorrhage. All patients underwent radical AVM surgical removal and hematoma evacuation in a single-stage procedure. Most patients (78%) were operated within the first day of hemorrhage. A favorable functional outcome (GOS: good recovery or moderate disability) was observed in 23 patients (85%). Mortality was 7.4%. Outcome was not significantly correlated with GCS at presentation and with presence of preoperative anisocoria.

Conclusions

Early surgery for grade I-II AVMs is a safe and definitive treatment, achieving both immediate cerebral decompression and patient protection against rebleeding, reducing time of hospital stay and allowing a more rapid rehabilitative course whenever necessary.     

Prolonged survival of porcine hepatocytes in cynomolgus monkeys

BACKGROUND & AIMS: Management of patients with liver failure can be a significant medical challenge, and transplantation of the liver is the only definitive therapy. Whole liver allotransplantation is limited by a shortage of human donors and the risks of the surgery in those most ill. Transplants consisting of xenogeneic hepatocytes might overcome these problems, and work in rodents indicates that such transplants can correct some metabolic deficiencies and can prevent the complications and mortality associated with hepatic failure. As a prelude to clinical application, we tested the feasibility of hepatocyte xenotransplantation in nonhuman primates. METHODS: One to 2 billion hepatocytes from outbred swine were transplanted into the spleens of cynomolgus monkeys using conventional immunosuppression to control rejection. Duration of graft function was determined based on assay for porcine albumin. RESULTS: Following a single infusion, xenogeneic hepatocytes functioned for more than 80 days and, following re-transplantation, for more than 253 days. Engraftment in the spleen was confirmed 40 days after transplantation by asialoglycoprotein receptor-directed nuclear scanning. The humoral immune response to the transplanted porcine cells had no discernible impact on the survival of the grafts. CONCLUSIONS: Xenotransplantation of hepatocytes should be explored as a readily available, minimally invasive form of therapy for hepatic failure.     

Culprit lesion plaque characterization and thrombus grading by high-definition intravascular ultrasound in patients with ST-segment elevation myocardial infarction

Background

Dedicated prospective studies investigating high-definition intravascular ultrasound (HD-IVUS)-guided primary percutaneous coronary intervention (PCI) are lacking. The aim of this study was to qualify and quantify culprit lesion plaque characteristics and thrombus using HD-IVUS in patients presenting with ST-segment elevation myocardial infarction (STEMI).

Methods

The SPECTRUM study is a prospective, single-center, observational cohort study investigating the impact of HD-IVUS-guided primary PCI in 200 STEMI patients (NCT05007535). The first 100 study patients with a de novo culprit lesion and a per-protocol mandated preintervention pullback directly after vessel wiring were subject to a predefined imaging analysis. Culprit lesion plaque characteristics and different thrombus types were assessed. An IVUS-derived thrombus score, including a 1-point adjudication for a long total thrombus length, long occlusive thrombus length, and large maximum thrombus angle, was developed to differentiate between low (0–1 points) and high (2–3 points) thrombus burden. Optimal cut-off values were obtained using receiver operating characteristic curves.

Results

The mean age was 63.5 (±12.1) years and 69 (69.0%) patients were male. The median culprit lesion length was 33.5 (22.8–38.9) mm. Plaque rupture and convex calcium were appreciated in 48 (48.0%) and 10 (10.0%) patients, respectively. Thrombus was observed in 91 (91.0%) patients (acute thrombus 3.3%; subacute thrombus 100.0%; organized thrombus 22.0%). High IVUS-derived thrombus burden was present in 37/91 (40.7%) patients and was associated with higher rates of impaired final thrombolysis in myocardial infarction flow (grade 0–2) (27.0% vs. 1.9%, p < 0.001).

Conclusions

HD-IVUS in patients presenting with STEMI allows detailed culprit lesion plaque characterization and thrombus grading that may guide tailored PCI.     

Allogeneic melanoma vaccine expressing alphaGal epitopes induces antitumor immunity to autologous antigens in mice without signs of toxicity

Owing to the absence of alphaGal epitopes in human cells and constant stimulation of the immune system by the symbiotic bacterial flora, humans develop high titers of natural antibodies against these epitopes. It has been demonstrated that syngeneic whole cell vaccines modified to express alphaGal epitopes could be used to generate a potent anticancer vaccine. In this study, we tested whether allogeneic whole cell cancer vaccines modified to express alphaGal epitopes would be effective for the treatment of murine melanoma. The alpha(1,3)galactosyltransferase (alphaGT) knockout mice (H-2) with preexisting subcutaneous and pulmonary tumors [alphaGal B16, H-2] received therapeutic vaccinations with S91M3alphaGal (H-2) whole cell allogeneic vaccines. These mice had better survival and reduced pulmonary metastasis burden compared with control mice treated with S91M3 vaccine cells. Vaccination with S91M3alphaGal-induced cytotoxic CD8 T cells recognizing the syngeneic alphaGal B16 tumors measured by adoptive transfer to recipients bearing pulmonary metastases. The presence of allo-antigens did not dominate the induction of immunity to "cryptic" tumor antigens and had helped in the generation of a more efficient vaccine to treat preexisting tumors when compared with classic autologous vaccines. Vaccination with allogeneic alphaGal vaccines did not induce signs of toxicity including changes in weight, hematology, chemistry, and histopathology of major perfused organs or autoimmunity in long-term murine models for breast, lung, and melanoma. This study established the safety and efficacy data of allogeneic alphaGal whole cell vaccines and constituted the basis for the initiation of human clinical trials to treat human malignancies.     

Periacetabular osteotomy and total hip arthroplasty in patients older than 40 years

The objective of this study was to investigate quality of life (QOL) in patients with dysplasia who were older than 40 years and who underwent Bernese periacetabular osteotomy (PAO). Quality of life was compared among 28 patients who underwent PAO and 33 patients of the same age who underwent total hip arthroplasty (THA). Outcome tools included the Western Ontario McMasters Universities (WOMAC) Osteoarthritis Index and the 12-Item Short-Form Health Survey. Seventy-three percent of PAO patients achieved a "very good" (75-100) outcome or a "good" (65-75) QOL score in pain dimension and 64% in function dimension at 4 years after operation. WOMAC pain (89 vs 71, P < .005) and function (90 vs 74, P < .005) scores were significantly better among THA patients (THA vs PAO). Although THA resulted in better QOL, osteotomy still provided excellent QOL outcome in a high percentage of patients older than 40 years. However, given the results of this study, in patients older than 40 years, periacetabular osteotomy should only be done in highly selected cases.     

Vascular compression of the oculomotor nerve disclosed by thin-slice magnetic resonance imaging

Purpose: To describe the thin-slice magnetic resonance imaging features of vascular compressive oculomotor nerve paresis.Methods: We performed thin-slice (2 mm thick) magnetic resonance imaging of the brainstem in a 74-year-old woman with right partial oculomotor nerve paresis using spoiled gradient recalled acquisition in the steady state.Results: Thin-slice magnetic resonance images disclosed that the right oculomotor nerve was compressed and dislocated superiorly and laterally by the tortuous basilar artery. No other abnormalities were observed.Conclusion: This is the first case report of vascular compressive oculomotor nerve paresis disclosed by thin-slice magnetic resonance imaging.     

Characterization of the p67phox gene: genomic organization and restriction fragment length polymorphism analysis for prenatal diagnosis in chronic granulomatous disease

The genetic defect in the p67phox-deficient form of chronic granulomatous disease (CGD) follows an autosomal recessive pattern of inheritance. When genomic DNA from normal individuals is digested with HindIII and probed with p67phox cDNA an allelic restriction fragment length polymorphism (RFLP) of 4.0 kb or 2.3 kb is detected. We cloned and characterized the p67phox gene using the cDNA and sequenced the exon/intron boundaries, mapping 16 exons on the 40-kb gene. The polymorphic region was then sequenced to identify the inheritance pattern of amniocentesis-derived fetal cells by genomic amplification. The proband, a 9-year-old female patient with p67phox-deficient CGD, and her phenotypically normal mother are homozygous for the RFLP marker, whereas the father and two brothers are heterozygous. The fetus was shown to be heterozygous as well, showing it had inherited at least one normal p67phox gene from the father and that it was predicted to have a normal phenotype. Cord blood samples at birth showed normal oxidative function. Amplification allows rapid detection of the inheritance pattern for fetal diagnosis in informative families. We report the genomic structure of p67phox and an amplification-based method for detection of the marker on chromosome 1q25, used here for prenatal diagnosis of CGD.