Isolation and characterization of an acquired antithrombin antibody

A 68-year-old man, following mitral valve replacement, presented with a low-grade chronic consumptive coagulopathy. Laboratory analysis showed mild fibrinolysis, minimal effect of coumadin therapy, and a prolonged thrombin time (greater than 150 seconds using bovine IIa). When purified human IIa was used the thrombin time normalized to within 17 seconds of controls, suggesting a possible inhibitor of bovine IIa. An anti-IIa antibody was isolated by protein A-Sepharose (Sigma, St Louis, MO) chromatography followed by affinity chromatography using a bovine IIa-Sepharose column. The effects of this purified anti-IIa antibody on both bovine and human IIa procoagulant and anticoagulant functions were studied. The isolated immunoglobulin G (IgG) was observed to inhibit bovine IIa in all assays tested. This IgG was also able to slightly prolong fibrinogen clotting by human IIa. Using an enzyme-linked immunosorbent assay it was observed that the IgG bound to bovine IIa, bovine II, human IIa, but not to human II. Further, binding was detectable at approximately 50-fold lower concentrations to bovine IIa (1 nmol/L IgG concentration) than to human IIa (50 nmol/L IgG concentration). The effect of the antibody on the reaction between IIa and AT III/heparin was investigated. Human IIa was found to be protected from AT III/heparin neutralization in the presence of this antibody. These results suggest that this patient developed an antibody that strongly binds to and inhibits the bovine IIa in all assays tested. However, the antibody only significantly affects human IIa neutralization by AT III/heparin, and has little effect on the human IIa procoagulant activity. These data suggest that the decreased effect of AT III/heparin on this patient's IIa may have been a contributing factor in his coagulopathy. The exact cause of this antibody development is unclear, but the role of bovine topical thrombin used during cardiac valve replacement surgery is suspect.     

Topical steroids for chronic wounds displaying abnormal inflammation

Introduction

Chronic, non-healing wounds are often characterised by an excessive, and detrimental, inflammatory response. We review our experience of using a combined topical steroid, antibiotic and antifungal preparation in the treatment of chronic wounds displaying abnormal and excessive inflammation.

Methods

A retrospective review was undertaken of all patients being treated with a topical preparation containing a steroid (clobetasone butyrate 0.05%), antibiotic and antifungal at a tertiary wound healing centre over a ten-year period. Patients were selected as the primary treating physician felt the wounds were displaying excessive inflammation. Healing rates were calculated for before and during this treatment period for each patient. Changes in symptom burden (pain, odour and exudate levels) following topical application were also calculated.

Results

Overall, 34 ulcers were identified from 25 individual patients (mean age: 65 years, range: 37–97 years) and 331 clinic visits were analysed, spanning a total time of 14,670 days (7,721 days ‘before treatment’ time, 6,949 days ‘during treatment’ time). Following treatment, 24 ulcers demonstrated faster rates of healing, 3 ulcers showed no significant change in healing rates and 7 were healing more slowly (p=0.0006). Treatment generally reduced the burden of pain and exudate, without affecting odour.

Conclusions

In normal wound healing, inflammation represents a transient but essential phase of tissue repair. In selected cases, direct application of a steroid containing agent has been shown to improve healing rates, presumably by curtailing this phase. Further evaluation is required to establish the role of preparations containing topical steroids without antimicrobials in the management of chronic wounds.     

Mesenchymal hamartoma of the liver: radiologic-pathologic correlation

Mesenchymal hamartoma of the liver (MHL) is an uncommon cystic mass of infancy that is a developmental anomaly rather than a neoplasm. Fourteen cases of MHL were retrospectively reviewed. Grossly, MHL is a solitary mass with cystic spaces of variable size. Patients are seen initially with painless progressive abdominal enlargement. On plain films, MHL appears as a large, noncalcified mass in the right upper quadrant. Scintigraphy is helpful in confirming its hepatic origin. Ultrasonography and computed tomography demonstrate a large multiloculated mass with considerable variation in the size of septa and cystic spaces. Angiographically, MHL is avascular or hypovascular. Recognition of these radiographic findings allows a correct diagnosis to be made in many cases. With resection, the prognosis is excellent.     

THE PSYCHOLOGICAL EFFECTS OF BREAST SCREENING IN TERMS OF PATIENTS' PERCEIVED HEALTH ANXIETIES

SUMMARY This study aimed to assess and compare the impact of letter of invitation, initial breast screening mammography, and subsequent recall procedures on the level of anxiety over breast problems. The survey of females undergoing routine breast screening procedures in a primary care setting is part of the first wave of a national breast screening programme in the UK. Women aged 50-64 registered with six general practices (n=2618) were invited by letter to attend for screening. Their self-perceived impact of receipt of invitation letter, attendance at initial screening, and recall, in terms of anxiety and concern about breast problems, was measured by a self-report questionnaire and the physical, emotional and social dysfunction subscales of the Psychological Consequences of Screening Mammography Questionnaire (PCQ). Overall, subjects' anxiety levels diminished between the receipt of their invitation letter and the completion of their screening examination. Subjects did not, however, respond to the letter of invitation and screening procedure in a homogeneous manner. In a sample of 1253, the letter of invitation reduced anxiety about breast problems in 39.7%, increased anxiety in 24.6%, and had no appreciable effect in 35.7%. In the 1280 who attended for breast screening, the examination procedure reduced anxiety about breast problems in 55.9%, increased anxiety in 12.8%, and had no appreciable effect in 31.3%. In a smaller sample (n=33) who completed questionnaires at recall, there were significant increases in PCQ-measured anxiety. Throughout the study, the PCQ was sensitive to change in anxiety over breast problems. We conclude that screening procedures can either increase or reduce anxiety about breast problems, or have no appreciable effect. Subjects' perception of the impact of receiving the letter of invitation and undergoing the screening examination procedure is related to previous levels of concern over breast problems. Conclusions about the psychological effect of breast screening cannot be drawn without consideration of the time and place of the baseline assessment. Participants in breast screening programmes therefore cannot be considered a homogeneous entity. Caution should be exercised when assessing the impact of screening procedures on entire populations as this approach might mask an important diversity of response.     

JunB as a potential mediator of PTHrP actions: new gene targets Ephrin B1 and VCAM‐1

Parathyroid hormone‐related protein (PTHrP) is an integral mediator of physiologic and pathologic processes and has demonstrated actions in the periodontium. PTHrP functions via AP‐1, and specifically through JunB. This study identified JunB‐dependent downstream mediators of PTHrP using OCCM cementoblastic transfectants with JunB over‐ or reduced expression. Over‐expressing cells showed an increase in proliferation, while the opposite was seen in siRNA transfected cells. Microarray analysis of over‐expressing cells revealed more than 1000 regulated genes. Three genes were investigated in more detail. The PTH/PTHrP receptor (PTHR1) and ephrin B1 (EfnB1) were down‐regulated, and vascular cell adhesion molecule‐1 (VCAM‐1) was up‐regulated with JunB over‐expression. JunB siRNA transfectants had increased PTHR1, but reduced ephrin B1 and unaltered VCAM‐1 in vitro. To validate these targets, parental OCCM cells and primary osteoblasts were treated with PTHrP, resulting in reduced PTHR1 and ephrin B1, and increased VCAM‐1. Cell transfectants were implanted subcutaneously in vivo, and microarray analysis and RT‐PCR performed. Over‐expression of JunB down‐regulated PTHR1 and ephrin B1, and increased VCAM‐1. JunB siRNA transfectant implants had increased PTHR1 and ephrin B1, but no altered VCAM‐1. These data highlight new gene targets for PTHrP and indicate JunB is a critical mediator of PTHrP actions.     

Muscular dystrophy misdiagnosed as hepatic disease in a child with coeliac disease

A 13-month-old boy presented with elevated serum aminotransferases and a flat small bowel mucosa indicating coeliac disease. He improved clinically on a gluten-free diet but serum aminotransferases continued to increase. This was found to be caused by an occult Duchenne muscular dystrophy. The case illustrates the fact that the finding of elevated serum aminotransferases in a coeliac child on a gluten-free diet should indicate that further investigations are needed to exclude coexisting disease.     

Intracervical versus vaginal misoprostol for cervical dilatation prior to operative hysteroscopy—a comparative study

Background

Hysteroscopic surgery requires pre-operative cervical ripening to facilitate adequate dilatation of the cervix for insertion of operative hysteroscope. This study was conducted to compare the efficacy of intracervical misoprostol with vaginal misoprostol in achieving cervical ripening before operative hysteroscopy.

Methods

In this randomised comparative study conducted at a tertiary care teaching hospital, 56 patients needing operative hysteroscopy were divided into two groups of 28 patients, one for intracervical misoprostol and the other for vaginal misoprostol. Four hundred microgram of misoprostol was inserted on the night before and in the morning of operative hysteroscopy intracervically in group I and vaginally in group II.

Results

Primary outcome measure was number of patients achieving 7 mm preoperative dilatation of cervix. Largest Hegar dilator that could be passed into the uterine cavity past the internal optic sheath without resistance was noted in each case. Mean cervical dilatation prior to operative hysteroscopy was calculated. In addition, incidence of slipping of vulsellum and cervical laceration was also noted. Time to achieve full cervical dilatation was recorded. In 23/28 cases of group I and 5/28 in group II, size 7 Hegar dilator could be passed without effort. Mean cervical dilatation was 7.5 mm in group I and 5.7 mm in group II. Slipping of the vulsellum and cervical lacerations were seen in significantly less patients in group I. Mean time to achieve cervical dilatation to 10 mm was 43.39 seconds in group I and 103.96 seconds in group II (P<0.0001).

Conclusion

Intracervical administration of misoprostol is an effective method of achieving cervical ripening for easy cervical dilatation up to 10 mm prior to operative hysteroscopy.