Pulse-generated runoff: a new method of determining calf vessel patency

A non-invasive method of determining calf vessel patency before femorodistal bypass has been developed. This pulse-generated runoff (PGR) system generates blood flow in patent calf arteries by means of a pulsatile cuff even if the existing Doppler signal is inaudible. PGR was compared with pre-operative arteriography in 95 ischaemic limbs and both were compared with the peripheral resistance measured at operation in 62 limbs. There was a highly significant correlation between the PGR and arteriogram scores (rs = 0.74, P less than 0.001) but PGR tended to detect more patent vessels than arteriography. The peripheral resistance correlated better with PGR than arteriography (rs = -0.71 and -0.54 respectively, P less than 0.001). PGR is a simple, non-invasive method of determining calf and foot vessel patency pre-operatively.     

A phase II study of sulofenur,a novel sulfonylurea,in recurrent epithelial ovarian cancer

Summary A total of 16 patients with recurrent epithelial ovarian cancer were treated with sulofenur (LY 186641), a novel oral sulfonylurea. All subjects had received previous chemotherapy. Anaemia occurred in all 16 patients, 14 of whom required a blood transfusion, and 2/16 patients received methylene blue for breathlessness due to methaemaglobinaemia. Treatment was discontinued in 2/16 cases due to rising liver enzyme values, which reverted to normal on cessation of the drug. There was no nausea or alopecia. Only two minor responses were seen. Plasma drug levels were insufficient to result in antitumour activity as extrapolated from animal data. Further studies that attempt to increase the bioavailability and improve the therapeutic index are warranted.     

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.      

Serological evidence that dry heating of clotting factor concentrates prevents transmission of non-A, non-B hepatitis

A new test for antibodies specific for an agent causing non-A, non-B hepatitis (NANBH) was used to screen 45 children with coagulation disorders who received factor concentrates. It was found that the test results correlated with clinical evidence of NANBH and that heat treatment of concentrates (80 degrees C for 72 hours) appears to have prevented transmission of NANBH.     

Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation

The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase; PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations. These mutations were scattered over the entire length of PTEN , with the exception of the first, fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region. Germline PTEN mutations were identified in four of seven (57%) BZS families studied. Interestingly, none of these mutations was observed in the PTPase core motif. It is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family. Genotype-phenotype studies were not performed on this small group of BZS families. However, genotype-phenotype analysis inthe group of CD families revealed two possible associations worthy of follow-up in independent analyses. The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvement (unaffected versus benign versus malignant). Specifically and more directly, an association was also observed between the presence of a PTEN mutation and malignant breast disease. Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families.      

高效液相色谱法测定小儿磨积片中橙皮苷的含量

目的:建立以高效液相色谱法测定小儿磨积片中橙皮苷含量的方法。方法:色谱柱为SpherisorbC18,流动相为甲醇-冰醋酸-水(25∶4∶71),检测波长为283nm,流速为2·0ml/min,柱温为50℃,灵敏度为0·16AUFS,进样量为20μl。结果:橙皮苷进样量在0·024μg~1·2μg范围内与峰面积积分值呈良好的线性关系(r=0·9999),平均回收率为99·1%(RSD=0·8%)。结论:本方法简便、快捷,灵敏度及准确度高,可为小儿磨积片质量控制提供依据。     

Development and feasibility of a sedentary behavior intervention for stroke: a case series

Background and Objective: High levels of sedentary behavior are prevalent among people with stroke and contribute to elevated risk for recurrent stroke. Few interventions reduce sedentary behavior post-stroke. The ABLE intervention aims to reduce sedentary behavior using activity monitoring, activity scheduling, problem-solving, and self-assessment to promote engagement in meaningful daily activities. The purpose of this study was to assess the feasibility (tolerability, acceptability, reliability, safety) of the ABLE intervention after stroke and describe trends in sedentary behavior at baseline and 4 weeks.

Clinical Presentation: Participants (n = 5) who were 6 months to 2 years post-stroke, ambulatory, and reported ≥6 h of daily sitting time.

Intervention: Twelve ABLE intervention sessions (3x/week for 4 weeks) conducted in participants’ homes. The ABLE intervention includes activity monitoring, activity scheduling, self-assessment, and collaborative problem-solving.

Results: All feasibility benchmarks were met for three participants. Two participants met tolerability and safety benchmarks but did not meet acceptability and reliability benchmarks. Variability in feasibility and sedentary behavior outcomes may be related to baseline levels of sedentary behavior and social support.

Conclusions: The ABLE intervention was tolerable and safe. The intervention protocol was refined to enhance reliability and acceptability. Future studies should estimate the effects of the ABLE intervention.     

A Narrative Review of Common Uses of Ophthalmic Ultrasound in Emergency Medicine

BackgroundThe timely evaluation of ocular conditions in the emergency department (ED) can be difficult due to a general lack of specialized equipment, trained personnel, and the time-sensitive nature of emergent ocular conditions. Recently, the use of ocular point-of-care ultrasound (POCUS) has been shown to be particularly useful in the ED. POCUS can be used to promptly diagnose various ocular pathologies, which include ocular trauma, vitreous hemorrhage, central retinal artery occlusion, and retinal detachment.ObjectivesThis narrative review seeks to inform the reader of current literature regarding the use of POCUS for the assessment of various ocular emergencies in the ED. The goal of this review is to provide the emergency physician with succinct and up-to-date information and instruction regarding the current uses of POCUS for patients presenting with particular ocular emergencies. Ocular pathologies that are common (ocular trauma) or for which ultrasound is particularly useful (such as retinal detachment) are discussed. Other ocular pathologies are also briefly discussed, such as central retinal artery occlusion, which is a promising new application for ultrasound evaluation.DiscussionThere have been many studies that provide evidence for the utility of POCUS in the evaluation of trauma and other ocular pathologies, including vitreous hemorrhage, retinal detachment, and central retinal artery occlusion.ConclusionsOcular POCUS is a useful modality in the evaluation of acute ocular complaints in the ED. Emergency physicians should be aware of these findings and feel confident in the utility of ocular POCUS in the ED.