bluuebunny/crossref_metadata_2025 huggingface dataset:
Laparoscopic ultrasonography in the management of ectopic pregnancy: is there a possible role?
Authors: Ahmed Ahmed A. , Lumb Michael R. , Williamson John G.
Published: March 2003

Objective 

Ectopic pregnancy is a potentially serious condition. The standard methods of diagnosis include estimation of the beta subunit of human chorionic gonadotrophin (β‐hCG), transvaginal ultrasonography (TVUS), and laparoscopy. Diagnostic laparoscopy yields up to 2% false‐positive and 4.5% false‐negative results with potentially serious consequences. Two cases where the technique of laparoscopic ultrasonography was used in the diagnosis of unruptured ectopic pregnancies are described.

Subjects 

Laparoscopic ultrasonography was used in cases of suspected ectopic pregnancy to confirm the diagnosis. A 60° convex array probe with multifrequency (5, 6.5 and 7.5 MHz) and a radius of curvature of 20 mm was used. The probe was introduced through a 10‐mm port.

Results 

The laparoscopic ultrasound probe could clearly detect early ectopic pregnancy. This technique is also superior to transvaginal ultrasonography in identifying an early intrauterine pregnancy.

Conclusion 

Our results suggest that laparoscopic ultrasonography may assist in the diagnosis of ectopic pregnancy when the findings at laparoscopy are uncertain.
The importance of histological diagnosis in patients with chronic pelvic pain and laparoscopic evidence of endometriosis
Authors: Shafik Amina , Ratcliffe Norman , Wright Jeremy T.
Published: March 2003

Objective 

To assess the accuracy of laparoscopic diagnosis of pelvic endometriosis by histological evaluation of biopsies excised from pelvic peritoneal lesions suspicious for endometriosis in patients with chronic pelvic pain.

Setting 

Centre for Endometriosis and Pelvic Pain, St Peter's Hospital, Chertsey, UK, between October 1997 and October 1998.

Subjects 

62 patients with the presenting complaint of chronic pelvic pain. These patients were included in the study irrespective of previous pelvic surgery or the earlier diagnosis of pelvic endometriosis.

Intervention 

Laparoscopic assessment and excision of peritoneal lesions suspicious for endometriosis. Excision biopsy of all suspected endometriotic lesions was laparoscopically performed using a sculpted tip Nd: YAG laser fibre. All procedures were undertaken under the direct supervision of the same senior laparoscopic surgeon. No major complication was encountered. The biopsies obtained were labelled according to the anatomical site and histologically examined by light microscopy for the presence of endometriosis.

Results 

We took 1–6 biopsies per patient and the total number of biopsies obtained was 150. Biopsies from three patients among the 62 were unsuitable for histological evaluation and were excluded from the study. In 43 patients (73%) there was histological confirmation of endometriosis in all or some of their biopsies. In all the biopsies from 14 patients (24%) there was no evidence of endometriosis, their biopsies comprising other tissues such as fibro‐fatty, fibrovascular and fibromuscular tissues. In two patients (3%) all their biopsies showed endosalpingiosis only. The commonest anatomical sites of pelvic peritoneal endometriotic lesions were the uterosacral ligaments, the pouch of Douglas, the medial broad ligaments, the intestinal serosa, and the ovarian fossae, respectively.

Conclusions 

The diagnosis of pelvic endometriosis in patients with chronic pelvic pain should be supported by excision biopsy and histological assessment, as the laparoscopic diagnosis is not always accurate. This would direct the clinician to the possible aetiology of the chronic pelvic pain and is of great value in counselling and planning future management for the patients.
Hysterectomy techniques and their effect on the blood markers of thrombogenicity
Authors: Singer Iain O. , Pringle Stewart , Tait R. Campbell , Moore Karen , Alexander Claire , Hawthorn Robert
Published: March 2003

Objective

The use of laparoscopic surgery appears to reduce patient trauma and permits earlier discharge. However, the operation may be longer and the overall effect on coagulation and the risk of thrombosis is not clear.

Design

We compared the effect on coagulation activation markers (thrombin–antithrombin, prothrombin fragments 1+2 and d‐dimers) and factors (protein C, antithrombin, fibrinogen and activated protein C resistance) of laparoscopic and open abdominal hysterectomy in 39 women for the week following surgery. Some of these are well‐recognised markers of thrombotic risk.

Results

We found no evidence to suggest that laparoscopic hysterectomy has a more favourable prothrombotic profile. There were no major differences between the surgical options.

Conclusions

Laparoscopic hysterectomy should be subject to the same rigour of thromboprophylaxis as open abdominal hysterectomy. We did find evidence of a prolonged prothrombotic state beyond the normal period of thromboprophylaxis in both groups.
Laparoscopic‐assisted vaginal hysterectomy for benign uterine pathologies: could this be the first‐line treatment?
Authors: Şimşek Tayup , Karakuş Cemil , Karaveli Şeyda , Trak Bilal
Published: March 2003

Hysterectomy is traditionally performed by the abdominal route, and is frequently done for benign uterine pathologies. Laparoscopic procedures have been used widely because of advances in technological development and increased laparoscopic experience. We therefore wished to evaluate the role of laparoscopic hysterectomy in comparison with traditional abdominal hysterectomy.

 A prospective study.

Department of Obstetrics and Gynaecology, Akdeniz University School of Medicine, Turkey.

We recorded details from all patients between 1998 and 2000 with indications for hysterectomy on account of benign uterine pathologies. Both types of hysterectomy were performed throughout this period. The operating times, complications and analgesia dosage were compared.

In all 84 patients underwent hysterectomy. Of these patients, 38 (45.2%) had laparoscopic‐assisted vaginal hysterectomy, 34 (40.4%) had total abdominal and 12 (14.2%) had vaginal hysterectomy. Laparoscopic hysterectomy showed the advantages of shorter hospital stay, less analgesic medication and earlier postoperative recovery.

 Laparoscopic hysterectomy, with the advantages of laparoscopic surgery, was the preferable approach to hysterectomy for benign uterine pathology in this series. It can replace traditional hysterectomy in patients who are suitable for laparoscopic surgery.
Long‐term success after open and laparoscopic colposuspension: a case–control study
Authors: Dietz Hans P. , Wilson Peter D.
Published: March 2003

Objective A decade after its development, laparoscopic colposuspension remains a controversial alternative to open colposuspension in the treatment of female genuine stress incontinence. Results from the few published randomized controlled trials vary considerably. The authors therefore intended to define long‐term subjective and objective results in their own patient population.

Design Clinical retrospective case–control trial.

Setting Urogynaecology service of a tertiary hospital.

Subjects 50 patients seen on average 3.3 years after laparoscopic colposuspension, matched with 50 women who had been followed up on average 3.4 years after open colposuspension.

Intervention Standardized interview, translabial ultrasound imaging.

Main outcome measures Incidence of urinary tract symptoms, bladder neck elevation and mobility, trigonal deformation, funnelling.

Results Stress and urge incontinence were non‐significantly more common after open colposuspension, with significantly less frequency and nocturia in the laparoscopic group (P = 0.02). Significantly more patients were completely asymptomatic after laparoscopic colposuspension (P = 0.03). On ultrasound imaging, open colposuspension appeared to more commonly result in permanent distortion of the trigone (P = 0.02), with significantly less bladder neck descent on Valsalva manoeuvre (P = 0.005). These parameters were independent of follow‐up time.

Conclusion It appears that, in the population assessed here, laparoscopic colposuspension seems to offer at least equivalent results when compared with open colposuspension.
Safe entry during laparoscopy: a prospective audit in a district general hospital
Authors: Jones Kevin D. , Fan Alfred , Sutton Christopher
Published: March 2003

Objectives To audit the implementation of a consensus guideline on safe entry during laparoscopy.

Design A prospective clinical study in a district general hospital, with a special interest in laparoscopic surgery for endometriosis.

Subjects and setting All patients undergoing a gynaecological laparoscopy at The Royal Surrey County Hospital between 1 February 2000 and 31 January 2001. Surgeons completed a standard form at the time of the procedure, and these were cross‐checked with patient discharge summaries, case notes and the hospital automated records.

Results At 12 months, the database included 470 patients. The Veress needle was inserted at the umbilicus in 458 (97.4%) of patients (343 at the base of the umbilicus and 115 subumbilically), and at Palmer's point in nine (1.9%), and in one patient access was gained through an open method. A suprapubic insertion was used in two patients. A gas pressure of 25 mmHg was used to establish a pneumoperitoneum in 299 patients (63.6%), and a volume technique was used in 167 patients (35.5%). All laparoscopies performed on the professional unit (C.S.) complied with the Middlesbrough guidelines. There were 23 (4.5%) complications related to the laparoscopy. Extraperitoneal insufflation occurred in 14 patients, and omental emphysema in four patients. A bowel injury occurred in two patients (0.42%), and uterine perforation in another two patients (0.42%). One procedure (0.21%) was converted to a laparotomy because of bleeding during treatment of an ectopic pregnancy. There were no vascular injuries, and no injuries occurred as a result of operative laparoscopic surgery.

Conclusion Apart from laparoscopies performed on the professional unit (C.S.), a large number of procedures did not comply with the recommendations of the Middlesbrough consensus, following implementation of the consensus guidelines.
Female adnexal tumour of probable Wolffian origin
Authors: Kim Kyong Jin , Jeong Dong Ki , Jang Byeung Woo , Lee Sung Ki , Kim Yoon Mi , Min Seong Ki , Nam Sang Lyun
Published: March 2003

Objective  Case report of unusual clinical and histological consequence of a female adnexal tumour of probable Wolffian origin (FATWO).

Subject  A 31‐year‐old woman with a 6 cm diameter adnexal tumour.

Interventions  The tumour was located within the leaves of the Fallopian tube. Excision was done using two atraumatic grasping forceps and bipolar coagulation.

Result  The duration of the operation was 70 min. Histological examination confirmed a FATWO.

Conclusion  FATWO may be low‐grade malignancies. The patient should be followed up regularly.
Menorrhagia in von Willebrand disease successfully treated with single daily dose tranexamic acid
Authors: Ong  , Hull  , Mayne
Published: March 2003

Four cases of menorrhagia in von Willebrand disease were successfully treated with tranexamic acid given in a single daily dose of 4 g for the first 3–5 days of the menstrual cycle. The pathophysiology and pharmacokinetics are discussed. The apparent improved efficacy and acceptability of this new dosing regime have been highlighted.
Two consecutive pregnancies and deliveries in a patient with von Willebrand's disease type 3
Authors: Caliezi  , Tsakiris  , Behringer  , KÜhne  , Marbet
Published: March 2003

Pregnancy and delivery are critical events in women with von Willebrand's disease type 3. Prophylactic treatment for delivery and early postpartum period is recommended. Vaginal delivery is considered safe. However, experience is based on rare case reports. We report the management of two pregnancies and successful deliveries in a woman with von Willebrand's disease type 3.
Evaluation of recombinant factor VIII (Kogenate®) stability for continuous infusion using a minipump infusion device
Authors: Hurst  , Zabor  , Malianni  , Miller
Published: March 2003

Continuous infusion of recombinant factor VIII (rFVIII) is desirable in clinical settings in order to maintain haemostatic levels in a cost‐effective manner. This study was designed to determine rFVIII stability over time using a minipump set‐up, which has been employed by clinicians for continuous infusion of rFVIII. Vials from three lots of Kogenate® (Bayer Corporation) were reconstituted in sterile water for injection, pooled and transferred to minipump infusion sets composed of either polyvinylchloride (Medex # IPR86/tube volume 0.5 mL) or polyethylene (McGraw S5904‐52, tube and adapter volume 2.1 mL), and held in temperature‐controlled rooms at 5 °C, 25 °C and 30 °C. Additional bags of rFVIII were prepared with heparin (4 U mL−1), and maintained at 30 °C. rFVIII was infused at a rate of 1.0 mL h−1. Samples were analysed for rFVIII activity over a 7‐day period at 0, 1, 15, 24, 78 and 168 h. Prior to the start of the timed study, rFVIII activity was measured in the lot pools and in the polyvinylchloride or polyethylene bags, and in the first flush volumes through the tubing. There was no difference in rFVIII activity measured in the pools compared to the bags. rFVIII levels in the initial 3‐mL infusion through the tubing showed a slight decrease in activity compared to the initial level which amounted to an insignificant loss of activity for the polyvinylchloride tubing but a significant loss in the polyethylene tubing (approximately 10 IU absolute loss in polyvinylchloride vs. 100 IU loss in polyethylene). After an initial flush of 1.0 mL for polyvinylchloride and 5.0 mL for polyethylene, activity returned to baseline and subsequently remained stable for all time points and temperatures from 5–30 °C over the 7‐day period. We conclude that the standard polyvinylchloride in polyethylene minipump bags and tubing provide excellent delivery and stability of rFVIII for continuous infusion with or without heparin, and can be used in hospital and ambulatory settings.
Clinical picture and treatment strategies in factor VII deficiency
Authors: Lee C. A. , Kessler C. M. , Varon D. , Martinowitz U. , Heim M. , INGERSLEV J. , KRISTENSEN H. L.
Published: March 2003

Summary. Factor VII is a trace protein required for normal haemostasis. Deficiency of factor VII comprises a highly heterogeneous disease group. Factor VII deficiency can cause bleeding, in particular if factor VII is extremely low, but a few cases lacking factor VII function entirely or subtotally may not present with a history of bleeding. Bleeding problems are not often reported in patients having a factor VII:C level at 10–15% of normal or more. Bleeding is frequently of mucocutaneous type, but the whole array of haemophilic bleeding may also occur. To control bleeding, during surgery in particular, substitution is required in the severe case of factor VII deficiency, but clinical studies documenting which correctional levels of factor VII:C to aim are lacking. It appears that a critical low level (trough) value at 10–15% may be anticipated, but clear documentation does not exist. Substitution programmes may include plasma or plasma derived factor IX concentrates of lower degrees of purity, so‐called prothrombin complex concentrates that also are relatively impure, and pure factor VII concentrates. An alternative is a recombinant factor VIIa molecule. However, this concentrate has not received license in a number of countries. Thrombotic manifestations appear to occur more often than expected in the factor VII deficient patients, some have been linked to the use of impure concentrates, others to preexisting thrombophilic risk factors, but some are unexplained and may bear a relationship to the deficiency state of factor VII itself. Controlled clinical trials are highly warranted in this rare bleeding condition.
Joint replacement for a spontaneously ankylosed hip in a haemophilic patient
Authors: RODRIGUEZ‐MERCHAN  , BLANCO  , SANJURJO  , MAGALLON
Published: March 2003

A cemented Charnley total hip prosthesis was implanted in a 48‐year‐old man with mild haemophilia (factor VIII 4 IU dL−1) in his right spontaneously ankylosed hip. At the time of surgery he was anti‐HCV positive, anti‐HIV negative, and no circulating inhibitors were encountered. The indication for surgery was long‐lasting intractable low back and ipsilateral knee pain. At 4‐month follow‐up, relief of pain was achieved as well as correction of limb‐length discrepancy, with a good result according to the Mayo Clinic hip score. Doses of 50 IU kg−1 body weight of recombinant factor VIII (Recombinate; Baxter, Glendale, California, USA) was used during the 2 weeks of admittance to the hospital. The dosage was adjusted according to the recoveries of factor VIII, with an overall factor consumption of 68 000 IU. As far as we know this is the first case reported in the literature of a person with haemophilia in whom a spontaneous hip ankylosis has been satisfactorily converted in a total hip arthroplasty with a short‐term follow‐up. However, a much longer follow‐up is still needed to ascertain the efficacy of this surgical procedure in haemophilia.
Orthotopic liver transplantation in a patient with severe haemophilia A and with advanced liver cirrhosis
Authors: Baudo  , Caimi  , Redaelli  , De Cataldo  , Somaini  , Rondinara  , Degasperi  , Bellati  , Belli  , Ideo  , Morfini  , Longo
Published: March 2003

A patient with severe haemophilia A underwent orthotopic liver transplantation because of changes correlated to end‐stage liver cirrhosis due to hepatitis B, C and D infection. Replacement therapy was carried out for 4 days and the clinical course was uneventful. At the time of reporting the patient has a normal working life. FVIII plasma concentration is normal. The indirect hyperbilirubinaemia may be related to the Gilbert’s anomaly of the donor.
Bleeding episodes in HIV‐positive patients taking HIV protease inhibitors: a case series
Authors: Racoosin  , Kessler
Published: March 2003

In July 1996 the Food and Drug Administration (FDA) alerted healthcare providers about 15 case reports of spontaneous bleeding episodes in HIV‐positive haemophiliacs taking HIV protease inhibitors. In order to characterize the bleeding associated with HIV protease inhibitor therapy, the FDA’s spontaneous adverse event reporting system was searched through 28 February 1997. The bleeding episode reporting rate for persons with haemophilia was compared for HIV protease inhibitors and zidovudine, and the characteristics of haemorrhagic events were compared between individuals with and without haemophilia. There was a substantial predominance of bleeding episodes for haemophiliacs taking HIV protease inhibitors (39 of 67; 58%) as compared with zidovudine (two of 63; 3.2%). A comparison of 39 reports of bleeding in haemophiliacs with 28 in non‐haemophiliacs revealed similarities in time to event and type of HIV protease inhibitor implicated, but differences were present concerning location of bleeding and outcome. A greater proportion of haemophiliacs had resolution of their bleeding following discontinuation of their HIV protease inhibitor and recurrence of bleeding following rechallenge, as compared with non‐haemophiliacs. HIV‐positive haemophiliacs appear to be at an elevated risk of bleeding while taking HIV protease inhibitors, but these medications may predispose all individuals to such complications.
Correction of fixed contractures during total knee arthroplasty in haemophiliacs
Authors: Rodriguez‐Merchan E.C.
Published: March 2003

Encouraging clinical experience has increased the indications for prosthetic knee arthroplasty in haemophiliacs. The medical status, physical disability, age and projected activity levels are the major factors in determining treatment for the patient with unilateral or bilateral haemophilic arthropathy of the knee. In more severely involved knees of patients with haemophilia, flexion contracture is a common deformity. In addition, valgus, external rotation deformity and posterior subluxation of the tibia may exist. The surgeon must have the expertise and experience to correct these deformities sufficiently when performing a total knee arthroplasty. A properly performed soft‐tissue release which achieves balance between the medial and lateral ligamentous structures and posterior capsule can provide stability to the knee with a semiconstrained prosthesis. In cases with severe deformity requiring resection of the posterior cruciate ligament a posterior cruciate substituting prosthesis may be necessary.
von Willebrand disease: an update in the Åland islandsSummary of a Nordic Symposium on von Willebrand disease, 24–25 September 1998, Mariehamn, Åland
Authors: Berntorp E. , Ingerslev J. , Schulman S.
Published: March 2003

In the past decades von Willebrand disease (vWD) has, in several respects, fallen into the shadow of classical haemophilia due to all problems that have faced those dealing with congenital bleeding disorders, not least regarding blood‐borne diseases. The time has come to revisit and refocus on vWD, probably the most common bleeding disorder. Accordingly, a number of Nordic physicians and scientists working in this field organized a meeting on the ferry boat from Stockholm to Mariehamn, in the Åland islands, the home of the index families with this disease, as described by Erik von Willebrand in 1926. The objective of the meeting was to make a comprehensive survey of vWD as seen from the situation in the Nordic countries. In order to achieve all goals some scientists of note from countries outside the Nordic area were invited as well.

This paper gives a summary of the symposium, mainly based on the separate papers published in this issue.
Severe factor V deficiency and neonatal intracranial haemorrhage: a case report
Authors: Salooja  , Martin  , Khair  , Liesner  , Hann
Published: March 2003

We report a case of severe factor V (FV) deficiency (<1%) associated with multiple episodes of intracranial bleeding which presented at birth. The clinical course was further complicated by the development of an inhibitor, episodes of sepsis and cardiac failure. The management using virally inactivated FFP and platelets is discussed.
Optimising local therapy during oral surgery in patients with von Willebrand disease: effective results from a retrospective analysis of 63 cases
Authors: Federici  , Sacco  , Stabile  , Carpenedo  , Zingaro  , Mannucci
Published: March 2003

Bleeding after dental extractions is very frequent in patients with von Willebrand disease (vWD) and in the past often necessitated transfusions with factor VIII/von Willebrand factor concentrates (vWFc). To evaluate the benefits of a standard local therapy on bleeding complications during oral surgery, 63 consecutive patients with vWD were analysed retrospectively. All types of vWD were included: type 1 (n=31), type 2 (n=22) and type 3 (n=10). All the patients had dental extractions or periodontal surgery at the same hospital by the same oral surgeons. All cases had been given tranexamic acid (TA) before and for 7 days after surgery. As additional local therapy fibrin glue (FG) was used during surgery in several patients. Additional systemic therapies were: desmopressin (DDAVP, 0.3 μg kg–1) and fVIII/vWF concentrates (vWFc, 40 U kg–1) given as a single dose before surgery. The 29 subjects (46%) treated locally did not bleed. Among the remaining cases, 24 (38%) were given DDAVP as additional systemic therapy and 6 (9.5%) received vWFc. There was bleeding after surgery in only two cases who had been given local FG (type 2 B) or systemic vWFc (type 3), but bleeding was stopped with an additional local application of FG. Our data suggest that a standard local therapy with TA and FG with DDAVP can prevent bleeding complications during oral surgery in the majority of patients (84%) with vWD and reduce the need for concentrates, with all their possible complications and high costs.
Synovectomy with rifampicine in haemophilic haemarthrosis
Authors: Fernandez‐Palazzi  , Rivas  , Viso  , De Bosch  , De Saez  , Boadas
Published: March 2003

The purpose of this paper was to assess the effectiveness of intra‐articular injected rifampicine® in haemophilic patients in order to achieve synovectomy by preventing repeated intra‐articular bleeding. We have used this technique in haemophilic patients previously and reported our results on 13 cases [
1]. Two hundred and fifty milligrams of rifampicine was injected into the elbow and ankle joints and 500 mg was injected into knee joints with 3–10 mL of lidocaine, depending on the joint size. The injections were repeated once a week for 7 weeks. Patients were only covered with antihaemophilic factor on the day of the injection at 30% above their coagulation level. We evaluated the results using two measures: subjective reports from the patient and objective assessment by the examiner. In the subjective reports the patient graded the results from their own perspective from 1 (poor) to 10 (excellent): 1–3, poor; 4–6, fair; 7–8, good; and 9–10, excellent. In the objective reports the grading was: excellent (‘dry joint’, full function, no haemarthrosis, no synovitis); good (clinical improvement, synovitis, reduction of haemarthroses, full function); fair synovitis (reduction of haemarthroses, no change in function); poor synovitis (persistent haemarthroses). This paper reports on the results of 38 patients with 39 joints with more that 3 years follow up, mean 1.8 years. There were 22 knees, nine elbows and eight ankles. Subjectively, there were excellent results in 21 joints (11 knees, six elbows and four ankles) good results in 15 joints (eight knees, three elbows and four ankles), fair results in two knees and a poor result in one knee. Objectively, results obtained were excellent in 20 joints (11 knees, six elbows and three ankles); good in 17 (nine knees, three elbows and five ankles); fair in one knee and poor in one knee.
Joint evaluation instruments for children and adults with haemophilia
Authors: Manco‐Johnson M. J. , Nuss R. , Funk Sharon , Murphy J.
Published: March 2003

With the heightened interest in protocols to prevent or treat complications of haemophilia related to recurrent haemarthroses, there is a need for sensitive joint‐evaluation tools. The World Federation of Haemophilia (WFH) Physical Joint Examination instrument, which was developed for persons with haemophilia worldwide, is not sensitive enough to detect early structural or functional abnormalities. Therefore, we have expanded the WFH instrument to detect more subtle abnormalities of joint structure and function, and in addition, developed a new scale specifically tailored to the dynamic growth and gait development of children. We compared the original and three new instruments in 43 children with haemophilia. The three new scales all showed better correlation with the WFH pain instrument than did the original WFH physical examination instrument (P < 0.01 for each of the new instruments vs. P > 0.05 for the WFH instrument). In addition, results of the new child physical examination instrument best conformed to a normal distribution (P=0.35) and this instrument had better overall statistical performance. This instrument should be studied further in prospective, longitudinal clinical trials of young children.
Sustained and therapeutic delivery of factor IX in nude haemophilia B mice by encapsulated C2C12 myoblasts: concurrent tumourigenesis
Authors: Hortelano G. , Wang L. , Xu N. , Ofosu F. A.
Published: March 2003

This study reports the generation of an immunodeficient murine model for haemophilia B, obtained by breeding factor IX‐deficient mice with an immunodeficient mouse strain, and use of this mouse model to evaluate the long‐term efficacy and safety of a gene therapy strategy for treating haemophilia B. Nude haemophilic mice were implanted with biocompatible microcapsules enclosing recombinant myoblasts secreting human factor IX. The activated partial thromboplastin time (APTT) of plasma of mice thus treated was invariably shortened 3 weeks after microcapsule implantation, and remained shortened for at least 77 days. Shortening of the APTT of the haemophilia mice coincided with the appearance of human factor IX in mice plasmas (up to 600 ng mL−1 on day 77), and normalization of the tail‐bleeding time. Thus, the microencapsulated myoblasts reversed the clinical phenotype of haemophilia B. In contrast, plasmas of immunocompetent haemophilic mice similarly implanted with microcapsules only showed a transient shortening of APTT, and coincident transient delivery of human factor IX antigen. Rapid disappearance of human factor IX from plasmas of immunocompetent mice also coincided with production of antibodies to the human transgene. Significantly, 86% of the nude haemophilia mice developed tumours of myoblast origin. Thus, while this study revealed the feasibility of this gene therapy approach to treat severe haemophilia B, it also highlights the importance of using safer cell lines to prevent tumour development.
Cost–utility analysis of recombinant factor VIIa (NovoSeven®) in six children with long‐standing inhibitors to factor VIII or IX
Authors: Ekert H. , Brewin T. , Boey W. , Davey P. , Tilden D.
Published: March 2003

The high cost of treating patients with inhibitors in an environment of restricted budgets warrants consideration of cost‐effectiveness. We determined the clinical response, effect on quality of life and the cost‐effectiveness of treatment with rFVIIa in six boys with long‐standing inhibitors to factors VIII or IX, compared with other treatment regimes previously used in these patients. The study used a longitudinal before‐and‐after design and was conducted in three phases. Phase 1 was 6 months preceding the introduction of rFVIIa, during which patients received on‐demand ‘usual care’ with other treatment regimes; phase 2 was 6 months treatment on rFVIIa assessed retrospectively; and phase 3 was 6 months on rfVIIa treatment assessed prospectively. Treatment with rFVIIa was reserved for intrarticular, compartment, psoas, mucosal and suspected intracranial bleeding. Treatment outcomes were obtained by interview using structured questionnaires, the quality‐of‐life instruments CHQ CF‐80 and CHQ PF‐50, patient self‐reporting diary, interrogation of hospital records, and the EuroQoL EQ‐5D for utility valuations. Our results confirm that rFVIIa is clinically effective and resulted in 63–92% reductions in the number of re‐treatments, duration of painful episodes, delay to initiation of treatment, days requiring wheelchair or crutches, emergency room visits and lost carer time compared with the patients’ other therapies. Quality‐of‐life improvements were observed in several important areas as perceived by both patients and their families, at an incremental cost per QALY of A$51 533.
Haemophilic pseudotumour of the paranasal sinuses: management with radiotherapy and factor replacement therapy
Authors: Gupta S. , Mohapatra B. B. , Ghai S. , Seith A. , Kashyap R. , Sharma R. , Choudhry V. P.
Published: March 2003

A case of pseudotumour of the paranasal sinuses occurring in a patient with haemophilia A is reported. There was a favourable response to combined treatment with radiation therapy and factor VIII replacement.
Total thrombin‐activatable fibrinolysis inhibitor (TAFI) antigen and pro‐TAFI in patients with haemophilia A
Authors: Antovic J. , Schulman S. , Eelde A. , Blombäck M.
Published: March 2003

Pro‐thrombin‐activatable fibrinolysis inhibitor (pro‐TAFI), also known as TAFI, procarboxypeptidase U, or procarboxypeptidase B, is a relatively recently described plasma glycoprotein synthesized in the liver. It can be catalysed into its active form, TAFI (TAFIa, carboxypeptidase U or B) by a complex of thrombin/thrombomodulin. TAFI can potentially inhibit fibrinolysis by removing carboxyterminal lysine residues from partially degraded fibrin, decreasing plasminogen binding on the surface of fibrin, which thereby results in a decrease of the fibrinolytic activity. As TAFI represents a connection between coagulation and fibrinolysis, it can be expected that TAFI levels are altered in different thrombotic and haemorrhagic diseases, such as haemophilia A. Total TAFI antigen (including pro‐TAFI, TAFI and the inactive form of TAFI [TAFIi]) and pro‐TAFI were determined in 17 patients with haemophilia A. Thirteen healthy age‐matched volunteers served as controls. No significant difference in levels of total TAFI antigen was observed between controls and patients with haemophilia, although it was slightly decreased in patients with haemophilia. Pro‐TAFI was significantly reduced in haemophilia patients compared to controls (P=0.0113). TAFI antigen levels similar to controls have already been described in different clinical conditions, including haemophilia A. Decrease of pro‐TAFI in haemophilia A can be an additional factor, together with decrease in thrombin generation, which induces impaired activation of pro‐TAFI to TAFI, and could cause accelerated fibrinolysis. This supports the validity of usage of antifibrinolytics in the treatment of haemophilia A. In this paper we use new nomenclature for TAFI, and we believe that this recommended terminology for different forms of TAFI can simplify further standardization in TAFI investigation.
Evolving perspectives in product safety for haemophilia
Authors: FARRUGIA A.
Published: March 2003

The past decade has seen a consolidation of the safety measures built into the manufacture of coagulation factor concentrates for people with haemophilia. The scientific developments of the 1980s have been fully reflected in the manufacturing principles and the regulatory control of concentrate production, so that the safety of concentrate therapy now exceeds the safety of normal blood transfusion. A clear understanding of the epidemiology of the transfusion‐transmitted viruses allows the selection of donors with a satisfactory safety profile. Source material for plasma‐derived concentrates is now screened with sensitive tests that detect viral infection in donors at a very early phase in the viral life cycle. This decreases the potential viral load to levels that are easily eliminated by well‐accredited viral inactivation procedures. These measures have ensured a high level of assurance regarding the safety of products from the traditional transfusion‐transmitted infections. However, testing for some transfusion‐transmitted viruses does not yet form part of mainstream blood screening; alternative strategies based upon the particular needs of pooled plasma product recipients may be more feasible. Whereas the risk of emerging pathogens has to be kept constantly under review, four such viruses identified over the 1990s have proven to be of little relevance to plasma product recipients and the need for measures specifically directed against them is debatable. The risk of variant Creuzfeldt–Jakob Disease (vCJD) is a special case of an emerging infection that is insufficiently well characterized to allow a conclusive assessment of its role in the safety of concentrates; however, data regarding the capacity of concentrate manufacturing methods to clear the putative agent are encouraging. The relative uncertainty surrounding vCJD has caused the influential regulatory authorities of North America to take a precautionary approach regarding the selection of blood donors. This is having an effect on the supply of factor VIII concentrates and has possibly affected the rate at which developed countries have switched to recombinant products. The safety of recombinant products continues to be supported through patient monitoring, and the new generation of plasma protein‐free products will further enhance the role of these products as the treatment of choice with people with haemophilia. However, their cost‐effectiveness relative to the current generation of plasma‐derived products makes it unlikely that they will be accessible by developing countries. The dependence of most of the world's population of people with haemophilia on a safe and sufficient blood supply will therefore continue into the foreseeable future, and with it the need to maintain constant vigilance on blood safety matters.
Modifier genes in haemophilia: their expansion in the human genome
Authors: TIZZANO E. F. , CORNET M. , DOMÈNECH M. , BAIGET M.
Published: March 2003

Mutations in factor VIII and IX genes have a determinant effect on the severity of haemophilia. Modulation of clinical manifestations depends on other genetic factors, including modifier genes. In the context of haemophilia, such genes could be the ones involved in thrombophilia. Factor V Leiden and prothrombin 20210A were studied as possible phenotypic modifiers. Inhibitor development after therapeutic factor replacement depends on the type of mutation and on the genetic factors related to the immune response of each patient. The study of all these variants in haemophiliacs constitutes an important step in prevention, prognosis and therapeutic alternatives of the disease.
Distribution of haemophilia in the French Basque country
Authors: Bauduer F. , Degioanni A. , Ducout L. , Scribans C. , Dutour O.
Published: March 2003

Summary. Because peculiar profiles for some genetic haematological diseases have been described among Basques, we aimed to investigate the distribution of haemophilia among this specific population. Hence, we retrospectively assessed all the cases of factor (F) VIII and FIX deficiencies seen in the French Basque country during a 16‐year period. Data on 41 patients with haemophilia (FVIII or FIX = 25%) were compiled. Incidence and prevalence for the whole population ranged within the classical limits (but with an unusually high A : B ratio) and tended to be slightly lower in autochthonous Basques (P = n.s.). Our data did not support significant differences in the distribution of this disease among French Basques.
Inherited coagulation disorders in southern Iran
Authors: Karimi M. , Yarmohammadi Hirad , Ardeshiri R. , Yarmohammadi Hooman
Published: March 2003

Summary.  A comprehensive survey concerning the Shiraz Hemophilia Society and the associated haemophilia treatment centre was undertaken in April 2002 to collect data on demographics, signs and symptoms in the southern Iranian population with haemophilia and allied disorders. The total number of patients with coagulation disorders was 367. Haemophilia A (factor [F] VIII deficiency) was found in 271, 39 had haemophilia B (FIX deficiency) and 24 had von Willebrand disease. The rare coagulation disorders (n = 33) included 11 patients with FX deficiency; 10 with FVII; six with FXIII; two with afibrinogenaemia; two with FXI; one with combined FVIII and FV; and one with combined FVII, FVIII and FIX deficiency. The prevalence was 6.64 per 100 000 inhabitants. The most common symptoms were haemarthrosis, haematomas and epistaxis. None of the patients were human immunodeficiency virus positive but 47 (15%) were hepatitis C virus positive and two (0.7%) were hepatitis B positive, so that the rate of transfusion‐transmitted infections was lower compared with other populations.
Efficacy of NovoSeven® during surgery on a haemophiliac with previous history of inhibitors
Authors: Saba H. I. , Morelli G. A. , Azam R. R. , Klein C. J. , Letson G. D.
Published: March 2003

Summary. Management of bleeding in haemophiliacs with a history of inhibitor remains problematic. With infusion of factor VIII (FVIII), development of an anamnestic response and possible appearance of high‐titre inhibitor remains a valid concern. We report a case of a haemophiliac with a history of moderately high‐titre FVIII inhibitor that had become undetectable. He had not received FVIII since 1997, when he became inhibitor negative. He had been managed during his bleeding episodes with prothrombin complex factor concentrates, which became less effective in controlling his bleeding. The patient had a history of recurrent, spontaneous shoulder joint dislocations with bleeding, pain and significant disability. Shoulder joint replacement surgery was suggested. Replacement therapy was discussed with the patient, who refused treatment with human FVIII because of his concern for possible anamnestic response and inhibitor rebound. Porcine FVIII was not acceptable due to his poor response when used once in the past, and his history of moderate allergic reaction. Therefore, recombinant factor VIIa (NovoSeven®, Novo Nordisk, Princeton, NJ) was considered to be an acceptable option for the contemplated shoulder surgery. The patient underwent 2.5 h of surgery with NovoSeven® infusion. The surgeons were impressed with the lack of bleeding in this traumatic surgery. Despite the continuously prolonged activated partial thromboplastin time and low FVIII levels, the patient maintained a remarkably dry surgical field. Effective haemostasis was achieved during and after this procedure. This case illustrates the usage of NovoSeven® as an effective treatment modality in a haemophilia A patient with past history of inhibitor undergoing joint surgery.
Experience with a new percutaneous port system, Percuseal®, for intravenous injection in patients with haemophilia, von Willebrand disease and severe alpha1‐antitrypsin deficiency
Authors: Berntorp E. , Piitulainen E. , Lethagen S. , Mattson E. , Tengborn L. , Mätzsch T.
Published: March 2003

Summary.  We have implanted a new port system (Percuseal®) in altogether 13 patients with haemophilia A, B, von Willebrand disease and alpha1‐antitrypsin deficiency in order to facilitate venous access. The Percuseal system differs from subcutaneous ports, such as Port‐a‐Cath, in that the upper part of the device protrudes above the skin. In this way, the patient can easily puncture the port membrane under the guidance of his eyes without penetrating the skin. In the present study cohort, a number of complications occurred. These were mainly caused by repeated local infections (in five patients), which made it necessary to replace the ports in three of the patients and to permanently remove the ports as the first option in two of the patients. In one patient, the port was removed because of inconvenience when doing physical exercise. In one additional patient, a severe systemic infection occurred, causing spondylitis. Despite the high infection rate, most patients considered the device very convenient to use. Because of the side‐effects seen in our study, the Percuseal port in its present form is not to be recommended for regular use. A reconstruction of the port, making it smaller and giving it an antibacteriostatic cap, may possibly make this kind of port system a feasible alternative to use in order to improve pharmacoeconomics in the prophylactic treatment of haemophilia and patients with alpha1‐antitrypsin deficiency.
The extracellular matrix can regulate vascular cell migration, proliferation, and survival: relationships to vascular disease
Authors: Raines Elaine W.
Published: March 2003

The extra
cellular
matrix (ECM) of the normal artery wall is a collection of fibrous proteins and associated glycoproteins embedded in a hydrated ground substance of glycosaminoglycans and proteoglycans. These distinct molecules are organized into a highly ordered network that are closely associated with the vascular cells that produce them. In addition to providing the architectural framework for the artery wall that imparts mechanical support and viscoelasticity, the ECM can regulate the behaviour of vascular cells, including their ability to migrate, proliferate and survive injury. The composition of the ECM is different within intimal lesions of atherosclerosis, which are composed of monocytes and lymphocytes from the circulation and
smooth
muscle
cells (SMC) that migrate from the media to the intima ( Ross 1993, 1999), and these differences may contribute to the altered phenotype of vascular cells within lesions. This review will briefly outline the ECM changes observed in atherosclerosis and restenosis and the potential relationship of these changes to altered vascular cell functions.
Hidden on the ward: the abuse of children in hospitals
Authors: Kendrick Andrew , Taylor Julie
Published: March 2003

Hidden on the ward: the abuse of children in hospitals

While there have been a small number of high profile cases of the abuse of children by hospital staff, there has been relatively little attention paid to the child protection issues for children staying in hospitals. Drawing on a conceptual framework from work on institutional abuse, we identify three types of abuse: physical and sexual abuse; programme abuse; and system abuse. Physical and sexual abuse can be perpetrated by medical professionals and hospital workers, it can be perpetrated by other children, or it can be perpetrated by the child’s own parent(s). Research evidence from the United States of America (USA) suggests that the rate of abuse in hospitals is higher than in the family home. Programme abuse occurs when treatment and care falls below normally accepted standards. Recently, a tragic case of programme abuse concerned the unacceptably high death rate of babies undergoing heart surgery at Bristol Royal Infirmary. System abuse is the most difficult to define but concerns the way in which child health services fail to meet the needs of children. Recent reports have highlighted inadequate services for children and young people, lack of priority given to children’s services, and geographical inequalities in the provision of services. Three crucial aspects in safeguarding children from abuse are highlighted: listening to children; the selection support and training of staff; and external systems of inspection, monitoring and standards. The recent British government agenda which has placed quality at the centre of National Health Service (NHS) developments are discussed. Only by addressing the abuse of children in hospital openly and honestly will effective child protection be possible.
Factors associated with students’ orientations to nursing
Authors: Vanhanen Liisa , Janhonen Sirpa
Published: March 2003

Factors associated with students’ orientations to nursing

This paper presents the results of a study focusing on the factors associated with orientations to nursing. Students’ orientations to nursing have not as yet been a focus of nursing research. In some other professions, however, professional orientation has been associated with learning motivation and study performance, and has been seen as a predictor of work satisfaction. In this study, students’ orientations to nursing were defined in terms of caring, nursing expertise and life orientation. The hypothesis of whether students’ pre‐educational experiences of nursing, gender, choice of nursing specialty, problems with nursing studies and intention to stay in nursing were associated with different orientations was tested. The extent to which students were orientated to caring, nursing expertise and their own life was also examined. The orientation to nursing measurement tool, which has been developed on the basis of a qualitative study, was used to collect the data. Nurse teachers collected the data from nursing students (n=184) who were studying in three different nursing programmes in Finland. Non‐parametric assessments (Mann–Whitney U‐test and Kruskal–Wallis test) of the differences between the students’ orientations were carried out. A majority of the students were highly life‐orientated, and two‐thirds had average nursing expertise or caring orientation scores. The results supported the study hypothesis of an association between students’ orientations and their gender, choice of nursing speciality, problems with nursing studies and intention to stay in nursing. However, the hypothesis of an association between students’ pre‐educational nursing experiences and orientation to nursing was not supported. The contradictions between students’ orientation to nursing and the philosophy of nursing underlying the study programme may be a source of motivational problems and dissatisfaction with nursing education. Therefore, nurse educators are challenged to discuss curriculum matters and student supervision in order to promote flexibility in planning personal study programmes.