Differences in T cell subsets between men and women with idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder, occurring predominantly in women. We studied by flow cytofluorimetry the T cell subsets in men and women with ITP and compared them with healthy sex-matched volunteers. In healthy controls, women were found to have higher proportions of T helper/inducer (Th/i) and lower T suppressor/cytotoxic (Ts/c) lymphocytes and consequently higher Th/i:Ts/c ratios than men. Accordingly, in clinical surveys, patients and controls should be matched for sex for proper comparisons. In patients with ITP in its active phase, an imbalance in T cell subsets was found in both sexes. The perturbation was more severe in women who had a marked decrease in number and proportion of Th/i lymphocytes and an increase in the proportion of Ts/c lymphocytes, whereas in men only, the proportion of Th/i lymphocytes was decreased. When patients with active disease were compared to those with ITP in remission, the decrease in Th/i subsets still persisted in both sexes but the Ts/c subset in women had returned to normal proportions. Therefore, the immune imbalance in ITP is more marked in women than men; imbalances in both Th/i and Ts/c are present in women while Ts/c appears not to be involved in men.     

Defective platelet-fibrinogen interaction in hereditary canine thrombopathia

A unique, intrinsic, hereditary canine platelet disorder attributable to abnormal fibrinogen receptor availability is described. Thrombopathic platelets from 13 severely affected basset hounds failed to aggregate in response to all agonists tested except thrombin. Normal platelet interaction with the various stimuli was inferred on the basis of their ability to elicit unimpaired shape change in thrombopathic platelets. No quantitative differences in major platelet membrane glycoproteins, intraplatelet fibrinogen, adenine nucleotides, or serotonin uptake were detected. Dense granule secretion was impaired. The ultrastructural appearance of thrombopathic platelets was normal. Fibrinogen-platelet interaction was evaluated by reacting platelet-rich plasma (PRP) with fibrinogen coupled to polymeric acrylonitrile beads and scoring the extent of stimulus-induced agglutination. The aggregatory responses of normal and thrombopathic platelets were closely correlated with fibrinogen receptor availability. In contrast to human platelets, epinephrine-stimulated canine platelets did not interact with immobilized fibrinogen, and arachidonate generally induced only weak agglutination. Thrombopathic platelets agglutinated fibrinogen beads at reduced rates when stimulated with physiologic doses of thrombin and high-dose calcium ionophore, A23187. Our data suggest that thrombin-mediated induction of canine platelet fibrinogen receptors may proceed by pathway(s) alternate to those shared by other platelet agonists, and/or that secreted granule constituents may act synergistically with thrombin to overcome inhibition of signal-response- coupled reactions mediating the interaction of fibrinogen with its receptor. This congenital platelet defect provides further evidence, in a species other than human, for the pivotal role of fibrinogen receptor induction in platelet aggregation.     

Molecular genetic rearrangements distinguish pre- and post-bone marrow transplantation lymphoproliferative processes

Chronic myelocytic leukemia (CML) may display a lymphoproliferative phase (lymphoid blast crisis) that is generally of B cell phenotype. Since lymphoproliferative disorders may occur following bone marrow transplantation (BMT), it may be difficult to distinguish posttransplant relapse of CML lymphoid blast crisis from de novo lymphoproliferation. Lymphoid blast crisis cells from a patient with CML displayed immunoglobulin heavy chain gene (C mu) rearrangement before BMT. Following BMT the patient developed a lymphoproliferative disorder involving multiple organs. Clonal rearrangement of C mu was demonstrated in several involved tissues. The rearranged C mu restriction fragment was distinct from that displayed before BMT. Additionally, rearrangement of the breakpoint cluster region (bcr) was demonstrated in the pretransplant blast crisis sample, but not in the posttransplant lymphoproliferation samples, thus confirming that these lymphoproliferative disorders were distinct. Molecular genetic techniques offer powerful diagnostic tools for monitoring the course of patients with CML undergoing BMT.     

Establishing a children's orthopaedic hospital for Malawi: A review after 10 years

Background

BEIT CURE International Hospital (BCIH) opened in 2002 providing orthopaedic surgical services to children in Malawi. This study reviews the hospital''s progress 10 years after establishment of operational services. In addition we assess the impact of the hospital''s Malawi national clubfoot programme (MNCP) and influence on orthopaedic training.

Methods

All operative paediatric procedures performed by BCIH services in the 10th operative year were included. Data on clubfoot clinic locations and number of patients treated were obtained from the MNCP. BCIH records were reviewed to identify the number of healthcare professionals who have received training at the BCIH.

Results

609 new patients were operated on in the 10th year of hospital service. Patients were treated from all regions; however 60% came from Southern regions compared with the 48% in the 5th year. Clubfoot, burn contracture and angular lower limb deformities were the three most common pathologies treated surgically. In total BCIH managed 9,842 patients surgically over a 10-year period. BCIH helped to establish and co-ordinate the MNCP since 2007. At present the program has a total of 29 clinics, which have treated 5748 patients. Furthermore, BCIH has overseen the full or partial training of 5 orthopaedic surgeons and 82 orthopaedic clinical officers in Malawi.

Conclusion

The BCIH has improved the care of paediatric patients in a country that prior to its establishment had no dedicated paediatric orthopaedic service, treating almost 10,000 patients surgically and 6,000 patients in the MNCP. This service has remained consistent over a 10-year period despite times of global austerity. Whilst the type of training placement offered at BCIH has changed in the last 10 years, the priority placed on training has remained paramount. The strategic impact of long-term training commitments are now being realised, in particular by the addition of Orthopaedic surgeons serving the nation.     

假细锥香茶菜新二萜成分——假细锥甲素的结构

从假细锥香茶菜(Rabdosia coetsoides C.Y.Wu)叶分离得到新二萜成分,根据紫外光谱、红外光谱、质谱、核磁共振氢谱及碳谱等分析,推定了化学结构,并经X-射线衍射确证,命名为假细锥甲素。     

Side effects of ergotamine

Ergotamine has been used for many years in the treatment of migraine, although there is little formal clinical evidence that it is significantly more efficacious than placebo. A number of side effects associated with ergotamine have been reported in the literature, including myocardial infarction, ischaemia of limb extremities, and fibrotic changes. Long-term use has led to reported cases of ergotamine-induced headache, vascular reactivity, and subclinical ergotism. When the safety profile of this drug is considered, coupled with its debatable efficacy from a clinical review previously published, the resulting poor risk: benefit ratio brings into question the continued use of ergotamine as a migraine treatment and calls for better controlled trials of its efficacy, or lack of, in the acute treatment of migraine.     

Visibility of gallstone fragments at US and fluoroscopy: implications for monitoring gallstone lithotripsy

To assess the value of ultrasound (US), fluoroscopy, and spot radiography in the detection, counting, and measurement of gallstone fragments during lithotripsy, in vitro visibility studies were conducted on fragments from 20 stones. Fluoroscopic visibility was evaluated during and after lithotripsy on 185 fragments placed in an anthropomorphic phantom. Three US experiments were performed on the fragments to study the visibility of fragments as a function of size, the accuracy of the count with large numbers of fragments, and the ability of observers to detect and count fragments larger than both 4 mm and 5 mm. With fluoroscopy, fragment detection rates ranged from 20% (fragments larger than 2.5 mm) to 80% (fragments larger than 4.5 mm). With US, all fragments larger than 1.5 mm were detected, and US was significantly better than fluoroscopy and spot radiography for detection of fragments 2.5 mm or smaller. US was also more accurate than fluoroscopy (11% vs 59% error) in the assessment of the number of fragments. When fragments larger than 4 mm or 5 mm were being counted with US, 92% of the fragments were visualized. The results suggest that US is more accurate for monitoring gallstone lithotripsy than fluoroscopy or spot radiography.     

Role of radiology in the treatment of malignant hilar biliary strictures 1: Review of the literature

Malignant strictures of the biliary tree are an uncommon cause of obstructive jaundice. There are a number of pathological subtypes, but tumours in this region tend to have similar clinical and diagnostic features and therapeutic and prognostic implications. We review the published literature on this topic discussing diagnostic modalities and treatment options with a focus on radiological intervention. Diagnosis currently is best achieved using a range of procedures. Direct cholangiography remains the gold standard in delineating anatomy, but the invasiveness of this procedure limits its use as a purely diagnostic tool. Magnetic resonance technology, in particular magnetic resonance cholangiopancreatography, has an increasing role as accessibility is improved. Treatment of these tumours is difficult. Surgical resection and palliative biliary enteric bypass are the most common methods used with endoscopic and percutaneous therapies reserved for palliating patients not fit for surgery. There is little firm evidence to suggest that any one palliative modality is superior. Interventional radiology is particularly suitable for palliative management of difficult and expansive lesions as the anatomy can preclude easy access by surgical or endoscopic techniques. Good palliative results with minimal mortality and morbidity can be achieved with percutaneous stenting .