The importance of determining the viability of the myocardium prior to revascularisation in patients with ischaemic cardiomyopathy and left ventricular systolic dysfunction

Chronic heart failure is a worldwide clinical syndrome with substantial socio-economical impact. The aim of this overview is the summary of contemporary knowledge in epidemiology, elementary pathophysiological implications and some possibilities of treatment of ischemic cardiomyopathy, which represents the most frequent cause of heart failure in developed countries. Emphasis is on the right indication for myocardial revascularization as a causal option of therapy of ischemic cardiomyopathy, timing and risk of revascularization and especially on importance of assessment of viability of myocardium using presently available imaging methods.     

Successful usage of tacrolimus (FK506) in resistant/relapsed rheumatic diseases

Aim: This study reports the first successful usage of tacrolimus in various resistant or relapsed rheumatic diseases in Asian patients Methods: This is an open prospective study of the efficacy of tacrolimus for patients with various relapsed/resistant rheumatic diseases who were intolerant of or failed conventional therapy. Patients were enrolled in the study from the period November 2001 to September 2002. Results: A total of 20 patients were included in the study. Their disease conditions were as follows: SLE with relapsed lupus nephritis (six patients); SLE with antiphospholipid syndrome (APS) (two patients); rheumatoid arthritis (five patients); psoriatic arthritis (three patients); scleroderma (two patients); anti–Jo?1 syndrome (two patients). Improvement in their conditions were noted in all but one patient who was intolerant to tacrolimus. Conclusions: Tacrolimus (FK506) is a new armamentarium that can be added to the choice of immunosuppressive agents for rheumatologists, especially for those patients with severe or resistant diseases.     

Exploring the utility of whole‐exome sequencing as a diagnostic tool in a child with atypical episodic muscle weakness

The advent of whole‐exome next‐generation sequencing (WES) has been pivotal for the molecular characterization of Mendelian disease; however, the clinical applicability of WES has remained relatively unexplored. We describe our exploration of WES as a diagnostic tool in a 3½‐year old female patient with a 2‐year history of episodic muscle weakness and paroxysmal dystonia who presented following a previous extensive but unrevealing diagnostic work‐up. WES was performed on the proband and her two parents. Parental exome data was used to filter potential de novo genomic events in the proband and suspected variants were confirmed using di‐deoxy sequencing. WES revealed a de novo non‐synonymous mutation in exon 21 of the calcium channel gene CACNA1S that has been previously reported in a single patient as a rare cause of atypical hypokalemic periodic paralysis. This was unexpected, as the proband's original differential diagnosis had included hypokalemic periodic paralysis, but clinical and laboratory features were equivocal, and standard clinical molecular testing for hypokalemic periodic paralysis and related disorders was negative. This report highlights the potential diagnostic utility of WES in clinical practice, with implications for the approach to similar diagnostic dilemmas in the future.     

Aetiology of acute febrile illness in children in a high malaria transmission area in West Africa

ObjectivesAreas with declining malaria transmission in sub-Saharan Africa have recently witnessed important changes in the aetiology of childhood acute febrile illness (AFI). We describe the aetiology of AFI in a high malaria transmission area in rural Burkina Faso.MethodsIn a prospective hospital-based diagnostic study, children aged 3 months to 15 years with AFI were recruited and assessed using a systematic diagnostic protocol, including blood cultures, whole blood PCR on a selection of bacterial pathogens, malaria diagnostics and a multiplex PCR on nasopharyngeal swabs targeting 21 viral and 4 bacterial respiratory pathogens.ResultsA total of 589 children with AFI were enrolled from whom an infectious disease was considered in 575 cases. Acute respiratory tract infections, malaria and invasive bacterial infections (IBI) accounted for 179 (31.1%), 175 (30.4%) and 75 (13%) of AFI cases respectively; 16 (21.3%) of IBI cases also had malarial parasitaemia. A viral pathogen was demonstrated from the nasopharynx in 157 children (90.7%) with respiratory tract symptoms. Of all children with viral respiratory tract infections, 154 (92.4% received antibiotics, whereas no antibiotic was provided in 13 (17%) of IBI cases.ConclusionsViral respiratory infections are a common cause of childhood AFI in high malaria transmission areas, next to malaria and IBI. These findings highlight the importance of interventions to improve targeted treatment with antimicrobials. Most patients with viral infections received antibiotics unnecessarily, while a considerable number with IBI did not receive antibiotics.     

Activated natural killer cells and interleukin-2 promote granulocytic and megakaryocytic reconstitution after syngeneic bone marrow transplantation in mice

Purified populations of natural killer (NK) cells were obtained from mice with severe combined immune deficiency (SCID). SCID spleen cells were cultured and activated with recombinant human interleukin-2 (rhIL- 2) in vitro. The activated NK cells were then transferred with syngeneic BALB/c bone marrow cells (BMC) and rhIL-2 into lethally irradiated syngeneic recipients to determine their effect on long-term hematopoietic reconstitution. On analysis, the transfer of rhIL-2- activated NK cells along with BMC resulted in significant increases in splenic and BM hematopoietic progenitor cells when compared with those for mice not receiving NK cells. Histologic and flow cytometric analysis showed a marked increase in granulocytic and megakaryocytic lineage cells present in the spleens of the mice receiving activated NK cells. Analysis of the peripheral blood indicated that the transfer of activated NK cells with BMC also significantly improved platelet and total white blood cell counts, with increases in segmented neutrophils. Erythroid recovery was not affected. Finally, lethally irradiated mice receiving activated NK cells and rhIL-2 along with limiting numbers of syngeneic BMC showed a marked increase in survival rate. These results show that the use of populations enriched for activated NK cells after syngeneic BM transplantation (BMT) has a profound enhancing effect on engraftment primarily affecting megakaryocytic and granulocytic cell reconstitution. Therefore, the transfer of activated NK cells and rhIL- 2 may be of clinical use to promote hematopoietic reconstitution after BMT.     

Effectiveness of methyl-GAG (methylglyoxal-bis[guanylhydrazone]) in patients with advanced malignant lymphoma

We treated 51 patients with advanced malignant lymphoma refractory to conventional therapy with methyl-glyoxal-bis(guanylhydrazone) (methyl- GAG) at doses ranging from 400 to 800 mg/sq m. Therapy was started on a weekly schedule and was switched to every other week in responding patients at the onset of toxicity. Partial responses were observed in 6 of 13 evaluable patients with Hodgkin's disease (46%), 5 of 10 patients with diffuse poorly differentiated lymphocytic lymphoma (50%), 2 of 4 patients with nodular poorly differentiated lymphocytic lymphoma (50%), and 3 of 13 patients with diffuse histiocytic lymphoma (23%). Two of six patients with mycosis fungoides showed objective improvement in cutaneous disease. Toxicity was generally mild and included muscular weakness, myalgia, mucositis, and diarrhea; two patients developed bronchospasm following drug infusions. We conclude that methyl-GAG has major antitumor activity when administered on this schedule to patients with advanced malignant lymphoma. The low degree of toxicity, unique mechanism of action, and minimal myelosuppressive effects suggest that methyl-GAG will prove useful in future trials of combination chemotherapy regimens for the treatment of lymphoma.     

射频消融房室结改良消融前后心脏电生理变化的探讨

目的比较房室结双径路伴房室结内折返性心动过速(AVNRT)患者,射频消融(RFCA)慢径路改良术,消融前、后心脏各部分腔内电生理改变。方法在相同条件下,于消融前、后分别进行腔内电生理检查。记录消融前、后:希氏束电图(HIS),心房有效不应期(A—ERP),功能不应期(A—FRP),心室有效不应期(V—ERP),功能不应期(V—FRP),房室结前传有效不应期(AVN—ERP),前传文氏点(AVN—WKB),房室结逆传有效不应期(VAN—ERP),逆传文氏点(VAN—WKB),将消融前、后心脏各部分电生理参数进行配对,经SPSS统计分析软件进行T检验分析。结果消融前、后:HIS电图,A—ERP,A—FRP,V—ERP,V—FRP,AVN—ERP,及VAN—WKB均无显著差异(P>0.05)。AVN—WKB,VAN—ERP有显著差异(P<0.05)。讨论射频消融房结改良对房室结双径路AVNRT疗效肯定。在消融前、后(急性期)房室结前、逆传电生理均有一定改变。这与消融改变了房室结的部分结构,如大部分病列慢径路消失有关。不同消融部位对房室结传导电理改变产生不同的结果。没有证据表明消融后,45岁以上年龄组房室结传导改变大于45岁以下年龄组。男女不同性别组之间亦无差异。