bluuebunny/crossref_metadata_2025 huggingface dataset:
Repetitive stereotactics: an inanimate laboratory technique to improve hand–eye coordination in laparoscopy
Authors: Kingston Ashley J. , Broome Jonathan D. , Vancaillie Thierry G.
Published: March 2003

Objective

To assess an inanimate laboratory technique to improve hand–eye coordination in laparoscopy.

Subjects

12 members of the medical staff at the Royal Hospital for Women, Sydney, were stratified into three groups: (1) young with no previous laparoscopic experience, i.e. first‐year resident; (2) young with some previous experience, i.e. registrar, and (3) mature with extensive experience in operative laparoscopy, i.e. established surgeon.

Methods

A planned, sequentially more difficult programme of hand–eye coordination exercises using a pelvi‐trainer was established. Performance was measured by recording the time taken for each subject to successfully and accurately complete each exercise.

Results

All subjects showed an improved performance in completing the described exercises. Group 1, showed the most improvement. Group 3 showed the least improvement but demonstrated the best performance. All groups demonstrated a similar performance by the end of the course.

Conclusion

The pelvi‐trainer in conjunction with a structured series of exercises appears to allow a trainee to improve hand–eye coordination significantly. Considering that the same equipment is used as that in the operating theatre, it is reasonable to expect similar improvement in actual surgery.
Removal of a broken intrauterine curette point
Authors: Oppelt P. , Stähler J. , Scharl A. , Kaufmann M.
Published: March 2003

The established method of surgical hysteroscopy today provides a modern and minimally invasive method of treating intrauterine pathology, which allows simple and unobtrusive therapy for pain, vaginal bleeding, and sterility caused by endometrial ossification, bony structures after abortion, and abruption, as well as for locating occult intrauterine devices. The case study presented here is the first description of hysteroscopic removal of a curette point which had broken off.
Complications of laparoscopy: a tautological audit
Authors: Tsaltas Jim , Healy David L. , Lloyd David
Published: March 2003

Objectives

The purpose of this study was to perform an audit continuing from the first series of 6500 consecutive laparoscopies from one centre. Since that time there have been a further 4448 consecutive laparoscopies at the same centre, making the total number 11 448 laparoscopies. The debate continues to rage concerning entry techniques at laparoscopy. One of the objectives of this study was to look again at the risks involved with the use of Veress needle and closed trocar entry techniques.

Design

All the major complications from laparoscopies performed between 1 April 1995 and 28 February 1999 were documented. This is again the largest series to date from any one centre. Each laparoscopy was registered on computer. A distinction between operative and diagnostic laparoscopy was not made.

Results

A major complication was defined as one which required laparotomy. In this second series, there was only one complication. The incidence of major complications was thus 0.2 per 1000. The incidence in our previous series was 1.23 per 1000. The combined incidence from both series is 0.78 major complications per 1000 cases. In neither series was there a vascular injury as a result of using a Veress needle or closed trocar entry technique.

Conclusion

This ongoing audit, and in particular the combined figures from both our audits, shows that there is currently no evidence to suggest that the Veress needle should be banned in favour of the open Hasson technique.
Recurrent laryngeal nerve paralysis after laparoscopic surgery
Authors: Yamada Takashi , Okamoto Yukiko , Kasamatsu Hajime , Umegaki Hiroshi , Mori Hiroshi
Published: March 2003

To present a case of recurrent laryngeal nerve paralysis after laparoscopic surgery.

A 26‐year‐old nulligravid woman.

The patient underwent laparoscopic left ovarian cystectomy and myomectomy under general anaesthesia. A few hours later, she complained of throat discomfort and hoarseness. Indirect laryngoscopy showed an immobile left vocal cord. The hoarseness continued for 4 weeks.

Recurrent laryngeal nerve paralysis might present as a complication of laparoscopic surgery under general anaesthesia.
A national survey of outpatient hysteroscopy
Authors: Rogerson Lynne , Duffy Sean
Published: March 2003

To look at the current practice in outpatient hysteroscopy, in particular to determine the availability, staffing levels, equipment used, and facilities throughout the UK, and to ascertain why the service is not more widely available for patients.

A postal questionnaire with no follow up for non‐responders.

National survey throughout the UK.

All consultant gynaecologists throughout the UK.

These were: the availability of outpatient hysteroscopy nationally; the reasons why outpatient hysteroscopy is presently not available in some units, and whether this facility was wanted in those units.

1148 questionnaires were mailed with 637 responses (55.5%), representing 80.7% of gynaecology units throughout the UK. Of the respondents, 55.6% had access to outpatient hysteroscopy, and of the respondents without access 77.7% would have liked the facility to be available. The reasons given for the lack of an outpatient hysteroscopy service were: lack of funding (35%); unavailable facilities (35%); alternative investigations employed (21.9%); not clinically appropriate (4.9%), and not cost‐effective (3.2%).

Outpatient hysteroscopy is available but its extent could be improved. The clinics are generally run once per week, with about six patients per clinic. It appears to be a consultant‐led service, and most of those consultants who do not have access to outpatient hysteroscopy would like the facility to be available but do not have the funding or facilities.
Hysteroscopic septal resection, the treatment of choice in patients with subseptate uterus: postoperative pregnancy rates
Authors: Oppelt Peter , Siebold Julia , Stähler Jan , Plathow Daniela , Kaufmann Manfred , Baumann Rudolf
Published: March 2003

Objective Hysteroscopic septal resection for subseptate uterus is a modern alternative to the classic procedures of Tompkins and Jones. We therefore investigated whether this new operation, which is less stressful for the patient, and can usually be carried out on an outpatient basis, can produce results similar to those of the classic laparotomy methods in patients receiving treatment for infertility.

Design Questionnaires were sent to 14 women who had undergone hysteroscopic surgery for infertility and known subseptate uterus at the University Department of Gynaecology in Frankfurt‐am‐Main.

Results Nine patients responded, six of whom had become pregnant after hysteroscopic resection of the septum. This corresponds to the results achieved with laparotomy methods.

Conclusion These results, like those of the few other studies on the topic in the literature, show that hysteroscopic septal resection in infertile patients offers a low‐stress, fast and outpatient alternative to the elaborate classic techniques of Tompkins and Jones.
Long‐term follow up of patients treated with intermediate FVIII concentrate BPL 8Y
Authors: Brown  , Dasani  , Collins
Published: March 2003

Long‐term surveillance studies of clotting factor concentrates are important to detect infrequent or delayed complications and to provide data against which newer products can be compared. We have assessed the long‐term use of BPL 8Y factor VIII (FVIII) concentrate (Bio Products Limited, Elstree, UK) in a cohort of 33 patients. These patients have been treated for a median of 96 months. They have received between one batch (in total) and 10 batches per year and between 1020 units (in total) and 116 700 units per year of BPL 8Y concentrate. No patient has developed a clinically significant FVIII inhibitor. There has been no evidence of transmission of hepatitis C, hepatitis B or HIV 1 or 2. Parvovirus B19 IgG antibody was present in 100% of the patients screened. Analysis of CD4 and CD8 lymphocyte subsets, using age‐related normal ranges, showed persistently depressed values in five patients, one of whom had a consistently low CD4/CD8 ratio.
Clotting factor concentrates and immune function in haemophilic patients
Authors: Hoots K. , Canty D.
Published: March 2003

Patients with haemophilia often exhibit a variety of disturbances in immune function. Although infections with HIV, hepatitis and other viruses no doubt contribute to these abnormalities, chronic exposure to extraneous proteins in clotting factor concentrates (CFCs) may also play a role. Numerous in vitro and ex vivo studies show that protein contaminants – such as immunoglobulins, fibrinogen and fibronectin – can depress various immune function indicators. Generally, such studies show that intermediate‐purity CFCs are more inhibitory than very high‐purity (e.g. monoclonal‐purified) CFCs. In many, but not all, studies, the degree of immunosuppression correlates with the amount of intermediate‐purity CFC administered over time.  Among various indicators of immune function, CD4+ lymphocyte number is a marker for the progression of HIV infection, and maintenance of CD4+ number is associated with delayed progression. A number of studies suggest that, compared with intermediate‐purity CFCs, use of very high‐purity CFCs is associated with longer preservation of this class of lymphocytes. However, it remains to be seen whether this translates to improved long‐term clinical outcomes.  Further research is needed on the impact of CFCs on the immune system. For the time being, however, evidence to date favours the use of very high‐purity products because they appear to preserve immune function and reduce the risk of infection with hepatitis and other viruses.
Prophylactic treatment in Sweden — overtreatment or optimal model?
Authors: Lee C. A. , Kessler C. M. , Varon D. , Martinowitz U. , Heim M. , LJUNG R. C. R.
Published: March 2003

Summary. At the haemophilia centre in Malmö, Sweden, regular prophylactic treatment is begun at 1–1½ years of age, before the onset of joint bleeds. The dose and dose interval are optimised by means of pharmacokinetic studies to determine the individual patient's FVIII or IX metabolism, the goal of maintaining a level <1% of normal being taken as a guideline which experience has shown to yield satisfactory control of bleeding diathesis. An optimal model for prophylactic treatment needs to be applicable to haemophiliacs and acceptable to health authorities in a majority of the countries in the world. To fulfill these criteria, the Swedish model, which has been shown to yield most satisfactory outcome, can hopefully be further refined in the future. Were continuous infusion, using a recombinate concentrate with a prolonged half‐life, technically feasible and socially acceptable to the child, we would probably have attained the optimal model of prophylactic treatment.
The destructive capabilities of the synovium in the haemophilic joint
Authors: Lee C. A. , Kessler C. M. , Varon D. , Martinowitz U. , Heim M. , RODRIGUEZ‐MERCHAN E. C.
Published: March 2003

Summary. The pathogenesis of chronic haemophilic synovitis and the destructive capabilities of the synovium are multifactorial. As a result of repeated haemarthroses, synovial hyperthrophy occurs, iron and cellular debris are phagocytized, and hydrolitic enzymes synthesized by the proliferating synovium are released into the joint. An inflammatory process develops, and the nutrition of the articular cartilage is affected by the abnormal synovial fluid, immobilization of the joint, and the presence of fibrous adhesions. Chronic hyperthrophic synovitis is a progressive destructive condition in the joint and, unless it is treated, the joint is doomed. With the development of cartilaginous destruction, progressive chondrolisis and eventual osteoarthritis set in.
Efficacy of viral clearance methods used in the manufacture of activated prothrombin complex concentrates: focus on AUTOPLEX® T
Authors: Horwith  , Revie
Published: March 2003

Various methods are described for the elimination of infectious viruses from activated prothrombin complex concentrates (aPCCs) and for the analysis of the final products (AUTOPLEX® T and FEIBA® VH). Viruses of concern in human plasma‐derived products are enveloped (hepatitis B and C, cytomegalovirus, Epstein–Barr virus, and human immunodeficiency virus [HIV]) and nonenveloped (hepatitis A and parvovirus B19). Donated blood used for AUTOPLEX® T is screened for antihepatitis C, HBsAg, anti‐HIV types 1 and 2, and p24 antigen. Plasma pools utilized for raw materials are also tested by PCR for HIV and hepatitis C virus. Partial virus inactivation and partitioning are achieved by purification of the aPCC. Further reduction of virus infectivity is accomplished by lyophilization and dry‐heat treatment. Each step undergoes virus elimination validation studies in which a relevant sample is ‘spiked’ with the appropriate virus or model virus. The total reduction in virus from raw material to final product can then be calculated. For AUTOPLEX® T the cumulative log10 reduction factors for several viruses vary from 4.2 to 14.3. This ensures an exceptionally high margin of safety. Definitive evidence for product safety was obtained by clinical observation of treated patients. The viral inactivation process of AUTOPLEX® T involves a four‐tier viral safety program, including Cohn alcohol fractionation and dry‐heat treatment, in place of the two‐stage vapour‐heating process for FEIBA®.
Factor VIII gene inversions and an XbaI polymorphism: nonradioactive detection and clinical usage
Authors: LIU  , THOMPSON
Published: March 2003

To simplify molecular diagnosis among families with severe haemophilia A, digoxigenin probe‐labelling and chemiluminescent detection was introduced. Sensitivity was the same as with 32P; background was lower. Of 33 previously untested families with severe haemophilia A, 15 have a factor VIII gene inversion (14 distal, one proximal). In three of the 13 families with isolated occurrence, de novo origin of the mutation was assigned to the maternal grandfather (two by XbaI linkage). Within the Seattle series, 64 (45% of 143) families with severe haemophilia A have an inversion; 15 are proximal. Fifteen patients from 12 families have had inhibitors; nine of these were > 10 Bethesda units per millilitre. All 36 mothers examined from the 43 families with isolated occurrence and nearly half (30 of 63) the daughters of an inversion carrier were carriers. Of 24 families where XbaI polymorphic analysis was performed for carrier assignment, 14 were informative. In families with severe haemophilia A, a nonradioactive, digoxygenin‐labelling system facilitates both factor VIII gene inversion and XbaI polymorphism analyses by Southern blots of digested, genomic DNA samples.
In vivo evaluation of a novel epitope‐tagged human factor VIII‐encoding adenoviral vector
Authors: Roy  , Shirley  , Connelly  , Andrews  , Kayda  , Gardner  , Kaleko
Published: March 2003

Haemophilia A is caused by a deficiency in coagulation factor VIII (FVIII) and is an attractive target for gene therapy. Adenoviral vectors encoding a human B‐domain deleted (BDD) FVIII cDNA have been shown previously to mediate expression of high levels of human FVIII and correct the bleeding defect in haemophiliac mice and dogs. While vector assessment in a non‐human primate model would have a significant preclinical benefit, a haemophiliac non‐human primate model is not available, and assays that distinguish human FVIII from monkey FVIII have not been developed successfully. As a first step to enable vector evaluation in non‐human primates, we have constructed an epitope‐tagged FVIII molecule by the addition of 16 amino‐acids to the carboxy terminus of the BDD protein (BDD‐E). Following vector administration to normal mice, therapeutic levels of BDD‐E FVIII were expressed for at least 20 weeks. Treatment of haemophiliac mice revealed that the BDD‐E protein was biologically active in vivo. To distinguish the BDD‐E protein from non‐human primate FVIII, a sensitive immunoprecipitation/Western assay was developed that reproducibly detected 1 ng mL–1 of the epitope‐tagged human FVIII in the presence of monkey plasma. These data demonstrate that the addition of an epitope tag had no effect on FVIII function or immunogenicity, and suggest that the BDD‐E vector will be an effective reagent for non‐human primate studies.
The impact of inhibitors on the cost of clotting factor replacement therapy in haemophilia A in Canada
Authors: Chang  , Sher  , Blanchette  , Teitel
Published: March 2003

A retrospective case controlled study was performed to determine the comparative costs of clotting factor concentrate therapy for haemophilia A patients with and without inhibitors. We examined treatment records for a 3.5‐year period for nine patients with factor VIII inhibitors and nine noninhibitor control patients matched for age and severity of disease. Inhibitor patients used FEIBA, porcine factor VIII, recombinant factor VIIa, and recombinant factor VIII over the study period. Controls used recombinant factor VIII and small amounts of monoclonal antibody purified plasma‐derived factor VIII and DDAVP. The total and mean cost for treating the nine inhibitor patients was 2.25‐fold greater than the cost for treating the controls. However, in six of the nine pairs the replacement product costs were actually less for the control patient than for the inhibitor patient, and the median cost of concentrates was comparable in the two groups (CDN$150 686 and $133 342 for inhibitor and control patients, respectively). This discrepancy was largely accounted for by a single inhibitor patient who required frequent hospitalizations for severe bleeding episodes. This individual, who did not receive an immune tolerance protocol, accounted for 62% of the total costs for the entire inhibitor group. In summary, over the study period the cost of haemostatic therapy for most inhibitor patients did not exceed that of control patients. However, due to the high per‐unit cost of the products used to treat inhibitor patients, the effect of individual outliers greatly magnifies the overall costs of treating patients with this complication.
Therapeutic embolization and surgical excision of haemophilic pseudotumour
Authors: Sevilla  , Alvarez  , Hernández  , Canales  , De Bustos  , Magallón  , Garzón  , Hernández‐Navarro
Published: March 2003

Haemophilic pseudotumour is a rare complication of haemophilia. Few cases of iliac haemophilic pseudotumour have been reported in the literature. These tumours can act as a focus for infection and cause cutaneous fistulas. When they present perforations and infections of endogenous origin their course is usually fatal.

Suitable treatment has been investigated on numerous occasions, most of the literature agreeing that the only curative treatment is surgical resection.

We present a case of haemophilic pseudotumour of the iliac and caecum with cutaneous fistulas, with a septic process of endogenous origin. It was treated with surgical resection after performing arterial embolization to reduce the vascularization of the pseudotumour, thereby reducing its size and the risk of bleeding complications during surgery.
Classification of von Willebrand disease: emerging issues
Authors: Holmberg L. , Lethagen S.
Published: March 2003

Among the three principal types of vWD, type 2 includes all qualitative abnormalities of vWF, and type 3 is the recessive form with total or near total absence. Type 1 with a purely quantitative reduction of vWF is considered to be the most common. As opposed to types 2 and 3, the molecular genetic background of type 1 has not been detected except in a few cases. We found that almost 25% of our patients diagnosed as type 1 vWD several years ago had the substitutions R611C och R552C recently labelled as type 2 mutations based on in vitro and/or clinical studies. The laboratory characteristics and the good response to DDVP, however, make them difficult to distinguish from type 1. Obviously, these substitutions confer only a minor and clinically insignificant functional deficiency of the vWF when present in heterozygous form. Based on this experience we question the clinical usefulness of the present vWD classification.
von Willebrand disease in Sweden: demography and treatment
Authors: Tengborn L.
Published: March 2003

Registration of patient with von Willebrand disease in Sweden is ongoing but far from completed. Forty‐seven patients with type 3 are diagnosed with coagulation assays. DNA studies performed at Karolinska Institute have shown that 21 type 3 probands were homozygous with the same mutation on the 2 alleles. If considering von Willebrand disease inherited as an autosomal dominant trait the number of heterozygous is calculated to 27 000. However, the mode of inheritance is not yet settled. Treatment with desmopressin+tranexamic acid in type 1 is highly efficient, as is the blood factor concentrate Haemate® (Centeon) in patients with type 3. Treatment in patients with type 2 must be individualized and is dependent on the response to desmopressin.
Controlling acute bleeding episodes with recombinant factor VIIa in Haemophiliacs with inhibitor: continuous infusion and bolus injection
Authors: Chuansumrit  , Isarangkura  , Angchaisuksiri  , Sriudomporn  , Tanpowpong  , Hathirat  , Jorgensen
Published: March 2003

The efficacy of recombinant activated factor VII (rFVIIa, NovoSeven) in five Haemophiliacs (four Haemophilia A, one Haemophilia B), with high inhibitors ranging from 70 to 1900 Bethesda units, was evaluated. The treatment regimen was divided into two groups: group I, continuous infusion of 16.5 μg h–1 kg–1 body weight (bw) after the initial bolus of 90 μg kg–1 bw in three episodes of severe bleeding and group II, bolus injection 80–150 μg kg–1 bw every 3 hours for a maximum of four doses in six haemarthroses. The bleeding was effectively controlled within 1 to 48 h in five of nine bleeding episodes. One patient in group I, who had active arterial bleeding requiring sutures, had an ineffective response and three patients in group II had partially effective responses because the rFVIIa was given after the onset of bleeding at 36, 44 and 72 h, respectively. The prothrombin time was shortened and the FVII:C levels were successfully achieved at approximately 10 U mL–1. The continuous infusion reduced the total dose of rFVIIa by 50%. Recurrent bleeding episodes were found in three patients; two occurred at the same site after ceasing rFVIIa for 51 h and while receiving rFVIIa at 144 h and one occurred at a new site after ceasing rFVIIa for 12 h.

Our experience would suggest that rFVIIa is effective in controlling acute bleeding episodes in Haemophiliacs with high inhibitors either by continuous infusion or bolus injection.
Influence of factor VIII:C and factor IX activity in plasmas of haemophilic dogs on the activated partial thromboplastin time measured with two commercial reagents
Authors: Mischke R.
Published: March 2003

The present study is based on 145 plasma samples with a reduced activity of factor VIII:C (range: 0.009–0.62 IU mL−1) and 28 samples with a reduced factor IX activity (range: 0.035–0.55 IU mL−1). The samples were collected from dogs with haemophilia A (n=22) or haemophilia B (n=3), some of these during substitution therapy. For all samples the activated partial thromboplastin time (APTT) was measured with two commercial reagents containing kaolin as a contact activator. In each case, the deficiency of factor VIII:C or IX was reflected in abnormal results of the APTT. This was true for both reagents. A significant correlation (P < 0.001) was found between factor VIII:C activity and APTT (reagent 1, Pathromtin®; Spearman’s rank correlation coefficient, rS=–0.731, reagent 2, PTT‐Reagenz; rS=−0.875) as well as between factor IX activity and APTT (reagent 1, rS=−0.819; reagent 2, rS=−0.955]. In each case, the relationship between coagulation factor activity and APTT could be proven most precisely by geometric regression. The results of this study illustrate the applicability of commercial APTT test kits as a sensitive screening test of factor VIII:C and IX deficiencies in canine plasma.
Mutation causing exon 15 skipping and partial exon 16 deletion in factor VIII transcript, and a method for direct mutation detection
Authors: Yenchitsomanus P. , Thanootarakul P. , Akkarapatumwong V. , Oranwiroon S. , Pung‐Amritt P. , Veerakul G. , Mahasandana C.
Published: March 2003

A splicing defect with 201 nucleotide deletion in the factor VIII transcript due to IVS15 + 1G > T mutation inactivating this donor splice site and activating a cryptic acceptor splice site in exon 16 was identified in a severe haemophilia A patient. Allele specific amplification (ASA) method was successfully developed for direct detection of this mutation.
Factor VIII concentrate inhibits T helper type 2 cytokine production in vitro: relevance to inhibitor antibody formation
Authors: Hodge G. , Han P.
Published: March 2003

Inhibitor antibody formation in patients with haemophilia receiving factor VIII (FVIII) concentrate is a serious problem. T helper type 2 (Th2) cytokines are necessary for antibody production by B cells and have been shown to be produced predominantly by CD30+/CD45RO+/CD3+ cells. We have previously shown that the Th2 cytokine, interleukin (IL)‐6, is inhibited but IL‐10 is upregulated, in the presence of plasma‐derived FVIII (pdFVIII). To clarify further the overall effect of FVIII on Th2 cytokine production, the percentage of T cells expressing the CD30+/CD45RO+/CD3+ Th2 phenotype was studied over 72 h and the production of the Th2 cytokines, IL‐4 and IL‐5, determined at 24 h in the presence of FVIII following whole‐blood stimulation using multiparameter flow cytometry. The production of IL‐4 and IL‐5 by T cells was significantly inhibited in the presence of pdFVIII. The percentage of CD30+/CD45RO+/CD3+ increased with stimulation of whole blood cultures over 72 h but was significantly inhibited by the presence of pdFVIII or TGF‐β at 72 h. The combined inhibitory effect of prednisolone (a commonly used immunosuppressive agent used to treat patients with inhibitors) with pdFVIII on T‐cell CD30+/CD45RO+ upregulation, was additive. There was no significant alteration in Th2 cytokine production or phenotype noted in the presence of recombinant FVIII (rFVIII) concentrate. Neutralizing antibody to TGF‐β significantly abrogated the inhibitory effects of pdFVIII on Th2 upregulation, indicating TGF‐β to be a major inhibitory component of pdFVIII on Th2 cytokine production. We now provide evidence that pdFVIII, by inhibiting Th2 cytokine production, may result in decreased antibody formation and may be more appropriate than rFVIII at reducing inhibitor formation. A clinical study needs to be undertaken to determine the significance of these in vitro findings.
The role of porcine factor VIII in the management of unexpected bleeding episodes
Authors: Aledort L.M.
Published: March 2003

The introduction of porcine factor VIII (pFVIII) has been an important addition to our armamentarium in the management of patients with inhibitors to FVIII. Case studies will be presented that offer important differential diagnoses. The prevalence and indications for the use of this biological replacement therapy will be discussed.
Haemophilia Utilization Group Study: assessment of functional health status in haemophilia
Authors: GLOBE D. R. , CUNNINGHAM W. E. , ANDERSEN R. , DIETRICH S. L. , CURTIS R. G. , PARISH K. L. , MILLER R. T. , SANDERS N. L. , KOMINSKI G.
Published: March 2003

The purpose of this study was to assess the relationship between health care and utilization of that health care, and to provide a base measurement of health status in patients with haemophilia. Provider interview and retrospective chart review of 336 patients with haemophilia treated during 1995 at one of five comprehensive haemophilia treatment centres was conducted to measure patient health status characteristics and utilization of health care. Two health status scales were included. The first, the Self‐Care Measure, was a four‐point single item scale measuring the patient's ability for basic self‐care, which was scored by a chart review and an interview with the health‐care provider. The second, the Haemophilia Utilization Group Study (HUGS) Functional Status Measure, is a four‐item, 10‐point scale developed specifically for patients with haemophilia. Our sample represents 27% of actively treated patients in region IX. The mean score on the HUGS Functional Status Measure was 8.7 (SD=2.4). The HUGS scale exhibited a ceiling effect across all four scales: attitude (n=269, 80.1%), overall wellbeing (n=263, 78.3%), working (n=254, 75.6%) and orthopaedic status (n=195, 58.0%). Both higher total health‐care costs and factor VIII annual costs were significantly associated with lower scores on the HUGS Functional Status Measure. Health status is a critical component in the assessment of the utilization and outcomes of care. In the absence of the availability of a patient interview, the HUGS Functional Status Measure can be used as one characteristic that explains the variation in the utilization of health care by patients with haemophilia.
Reproductive choices for couples with haemophilia
Authors: O. Oyesiku J. O. , Turner C. F.
Published: March 2003

Summary. The impact of having a child with an inherited bleeding disorder such as haemophilia can have a far‐reaching effect on the individual as well as other close family members. This situation is further complicated in the case of human immunodeficiency (HIV) serodiscordant couples, where the haemophilic man is affected with HIV through infected blood products whilst his partner is seronegative and wanting to have children.

It is essential that information on the effects of haemophilia, its inheritance, the possibilities of antenatal diagnosis, the consideration of selective abortion and the new reproductive opportunities available to these couples are made accessible so that an informed decision about proceeding with having a family can be made.

Couples may wish to have a family through nonreproductive methods such as fostering or adoption. Alternatively, they may wish to remain childless. In this paper, the terms ‘having children’ and ‘having a family’ will refer to conception through biological reproduction.

Pre‐implantation genetic diagnosis (PGD) offers families at risk of having a child with certain inherited genetic disorders the opportunity to give birth to an unaffected child. It may be considered as an option for couples who would not wish to have prenatal diagnosis leading to possible termination of a pregnancy.

Assisted conception techniques, such as ‘sperm washing’ or the use of ‘donor sperm’, offer serodiscordant couples affected by HIV a risk‐reduced or risk‐free opportunity, respectively, to have a child without infecting the mother, who could in turn infect the fetus by vertical transmission.

This article, in addition to outlining the inheritance of haemophilia and the more common prenatal screening and diagnostic tests, discusses in more detail the latest reproductive opportunities available for families affected by haemophilia and considering having a family.
Haemophilia in the developing world: the Brazilian experience
Authors: Antunes S. V.
Published: March 2003

Summary.  The success of haemophilia treatment is based on well‐established criteria, and the use of clotting factor concentrates is fundamental. These strategies are seen in the developed world when measures of quality of life are studied or when disabilities are evaluated among haemophilic patients. At the same time, countries in the developing world, with almost 80% of the haemophilia population, are making tremendous efforts to change their diagnosis and treatment methods, in order to improve their healthcare and therefore be able to promote better life for haemophiliacs. However, these goals are threatened when there are many social needs and few economic resources. There is wide variation in conditions in these countries, depending on what has already been done, how many patients the country has, how the blood banking services are planned and obviously, what are the interested parties. Even with so many difficulties, there are ways to work towards and reach the most important goal, which is to prepare the haemophiliacs to be citizens that are as productive and capable of working as are the nonhaemophiliacs. Each country has to take its part; the commitment of the community, physicians and government will be needed to design a model that is compatible with all the necessities and possibilities, and is understood by all the persons involved.
The impacts of people and livestock on topographically diverse open wood‐ and shrub‐lands in arid north‐west Namibia
Authors: Sullivan Sian
Published: March 2003

1. It is generally considered that the open woodlands of north‐west Namibia are experiencing widespread degradation due to over‐use of resources by local herders.

2. Data are presented regarding community floristics, diversity, density, cover and population structure for woody vegetation. These are analysed in relation to abiotic factors of topography and substrate, and to settlement impacts represented indirectly by distance from settlement and directly by measures of branch cutting and browsing.

3. None of the vegetation indices upheld predicted patterns of degradation except on a small scale, confined to within settlements. Moreover, in nearly all cases, local settlement effects were within the range of variability observed at larger scales.

4. It is concluded that continuing perceptions and fears of degradation in this area relate more to ideology than evidence. In particular, it is argued that factors conferring resilience and persistence on both the environment and the regional herding economy are obscured by: (1) disregard for the implications of spatial and temporal scale in interpretations of ecological data; (2) a conceptual adherence to equilibrium dynamics that stresses density‐dependent impacts of people and livestock over and above the role of abiotic factors in constraining and driving primary productivity; and (3) remnants of a colonial ideology, which tends to view ‘traditional communal farming’ practices as environmentally degrading.
Implications of land use change for the production of plant biomass in densely populated Sahelo‐Sudanian shrub‐grasslands in north‐east Nigeria
Authors: Mortimore Michael , Harris Frances M. A. , Turner Beryl
Published: March 2003

The production of plant biomass on small farms and in woodland in densely populated locations in the Nigerian Sahelo‐Sudan is estimated in order to test the hypothesis that conversion of land from natural vegetation to cultivation entails a loss in plant productivity. Estimates are given for reserved forest, woodland, shrubland and farmland at two sites varying in mean annual rainfall and population density. The results fail to support the hypothesis. The role of farmers in causing degradation through loss of plant productivity, and appropriate conservation strategies, may require re‐evaluation.
Macroecology and consilience
Authors: Maurer Brian A.
Published: March 2003

Consilience means that all fields of human knowledge should be internally consistent. Within the broad span of the ecological and evolutionary sciences, there are many fields that seem only remotely related conceptually. Macroecology has emerged as a research programme that focuses on statistical patterns of ecological and biogeographically relevant traits among different species within a taxon. The concepts needed to understand these patterns require the interface of disciplines as different as systematics, ecosystem ecology, palaeontology and community ecology. By building conceptual links among a wide range of disciplines, macroecology is contributing, and will continue to contribute, to the growing realization that all of biology is indeed consilient.
Airways hyper‐responsiveness to bradykinin and methacholine: effects of inhaled fluticasone
Authors: Reynolds C. J. , Togias A. , Proud D.
Published: March 2003

Background Although inhaled corticosteroids are the most effective anti‐inflammatory agents available for the treatment of asthma, they have, at best, only modest effects on airways responsiveness to methacholine. Thus, hyper‐responsiveness to methacholine is a relatively insensitive monitor of the effectiveness of glucocorticoids in asthmatic subjects.

Objective The study aimed to determine if airways hyper‐responsiveness to bradykinin provides a more sensitive index of glucocorticoid responsiveness in asthmatic subjects than does hyper‐responsiveness to methacholine.

Methods A double‐blind, placebo‐controlled, parallel group study comparing the effects of inhaled fluticasone (220 µg twice daily) on responsiveness to the two stimuli in asthmatic subjects who had never previously received corticosteroid therapy. Drug (n = 13) or placebo (n = 12) were administered for 16 weeks. Responsiveness to bradykinin and methacholine was determined at baseline and at 4 week intervals.

Results Placebo did not alter responsiveness to either stimulus compared to baseline. Fluticasone treatment significantly reduced responsiveness to bradykinin (P < 0.001 by Friedman anova) and methacholine (P = 0.02), but changes in responsiveness to bradykinin were significantly greater than those in methacholine responsiveness (P = 0.002). Bradykinin responsiveness was decreased at all treatment times compared to baseline, while methacholine responsiveness was not decreased until 8 weeks of therapy. When data were analyzed as changes from baseline (ΔLog PD20), ΔLog PD20 for methacholine was not different at any time‐point between the two treatment groups. By contrast, ΔLog PD20 for bradykinin was significantly greater in patients receiving fluticasone compared to those on placebo at all but the 16‐week treatment time. Ten of 13 subjects receiving fluticasone failed, on at least one post‐treatment visit, to show a 20% fall in forced expiratory volume (FEV1), even at the highest dose of bradykinin.

Conclusions Airways responsiveness to bradykinin is more profoundly, and more rapidly, reduced by inhaled glucocorticoids than is responsiveness to methacholine. Airways hyper‐responsiveness to bradykinin provides a convenient and sensitive monitor of glucocorticoid responsiveness in asthma.
Analysis of association and linkage for the interleukin‐4 and interleukin‐4 receptor balpha; regions in Swedish atopic dermatitis families
Authors: Söderhäll C. , Bradley M. , Kockum I. , Luthman H. , Wahlgren C.‐F. , Nordenskjöld M.
Published: March 2003

Background Atopic dermatitis (AD) is caused by genetic and environmental factors that interact to determine disease susceptibility and severity. Several lines of evidence suggest that the IL‐4 gene and the IL‐4‐receptor alpha (IL‐4Rα) gene are involved in the development of atopic diseases.

Objective The objective of this study was to evaluate the possible involvement of the chromosomal regions 5q31 and 16p12, which include the genes coding for the IL‐4 and the IL‐4Rα in AD.

Methods We conducted linkage analysis and association studies using the microsatellite markers D16S298 and D16S403 and a single nucleotide polymorphism in the promoter region of the IL‐4 gene (− 590C/T) in 406 Swedish families with at least two siblings affected with AD, in total 1514 individuals.

Results and Conclusion We report linkage (P < 0.005) to the − 590C/T polymorphism in the promoter of the IL‐4 gene for the semiquantitative trait severity score of AD. Neither linkage nor association was found to the IL‐4Rα chromosomal region.
The skin fungus‐induced Th1‐ and Th2‐related cytokine, chemokine and prostaglandin E2 production in peripheral blood mononuclear cells from patients with atopic dermatitis and psoriasis vulgaris
Authors: Kanda N. , Tani K. , Enomoto U. , Nakai K. , Watanabe S.
Published: March 2003

Background It is suggested that skin fungi may be involved in the development of atopic dermatitis (AD) and psoriasis vulgaris (PV).

Objective We studied skin fungus‐induced Th1‐ or Th2‐related cytokine, chemokine and prostaglandin E2 (PGE2) secretion in peripheral blood mononuclear cells (PBMC) from patients with AD and PV and normal subjects.

Methods PBMC were cultured with the extracts of Malassezia furfur (MF), Candida albicans (CA) and Trichophyton rubrum (TR). The cytokine, chemokine and PGE2 amounts in the supernatants were measured by enzyme‐linked immunosorbent assays.

Results MF induced IL‐4 and macrophage‐derived chemokine (MDC) secretion in AD patients, while induced IFN‐γ and interferon‐inducible protein of 10 kDa (IP‐10) secretion in PV patients, however, did not induce either secretion in normal subjects. CA induced IL‐4, MDC, IFN‐γ and IP‐10 secretion in AD and PV patients and normal subjects. In AD patients, the magnitude of IL‐4 and MDC responses to CA was higher than that to MF. Compared with PV patients and normal subjects, the magnitude of IL‐4 and MDC responses to CA was higher while that of IFN‐γ and IP‐10 responses to CA was lower in AD patients. TR induced moderate IL‐4 and MDC secretion only in AD patients. The three fungi induced higher levels of PGE2 secretion in AD patients than in PV patients and normal subjects. Cyclooxygenase‐2 inhibitor NS‐398 suppressed PGE2 responses to MF, CA and TR, and partially suppressed IL‐4 and MDC responses to MF, CA and TR, while enhanced IFN‐γ and IP‐10 responses to CA in AD patients, and these effects of NS‐398 were reversed by cyclic AMP analogue.

Conclusion AD patients manifest Th2‐skewed responses to MF, CA and TR, which may be partially attributable to the enhanced PGE2 responses to these fungi. PV patients manifest Th1‐skewed responses to MF.
MacroCAIC: revealing correlates of species richness by comparative analysis
Authors: Agapow Paul‐Michael , Isaac Nick J. B.
Published: March 2003

Abstract.Studies of species richness have been hampered by the use of methods that fail to account for phylogenetic non‐independence of character states. MacroCAIC is a computer program that extends the method of phylogenetically independent contrasts to encompass species‐richness data. It examines user‐selected characters for correlation with species richness, thus allowing clearer identification of the factors driving large‐scale patterns of diversity.
A survey of women's preferences regarding alternative surgical treatments for menorrhagia
Authors: Sculpher Mark J , Dwyer Nuala , Browning James , Horsley Sue , Cullimore John
Published: March 2003

Background

Menorrhagia represents a major health burden to a large number of women in the UK. A range of medical and surgical treatments is now available for the condition, but each has its own advantages and limitations.

Methods

A postal survey was undertaken of women with apparently uncomplicated menorrhagia referred to one of two NHS hospitals. The aim was to elicit women's preferences for the characteristics of surgical treatment and, specifically, to assess how they traded‐off the characteristics of hysterectomy and minimal access surgery.

Results

A total of 221 women returned their questionnaire and were included in the study (59% of those sent out). The characteristics most frequently rated as `very important' were getting back to usual activities as soon as possible (57%), experiencing the least pain and discomfort (46%), spending a short time in hospital (46%) and stopping periods for good (43%). The single characteristic most frequently rated as the most important by women was stopping periods for good (28%). Similar proportions of women preferred abdominal hysterectomy (43%) and endometrial resection (41%) when these were described to them. When asked to think about specific treatments of which they were aware, strong positive (43%) and negative (42%) preferences were indicated. Women's main information source was their general practitioner (70%), but only 44% considered themselves well‐informed about menorrhagia and its treatment.

Conclusions

Many women referred to hospital with menorrhagia have conflicting objectives for treatment, feel under‐informed about therapies and have not formed treatment preferences. It is important to develop well‐structured and accessible sources of information for women and methods to elicit their treatment preferences, and to evaluate the impact of such tools on treatment selection and outcomes.
Attitudes to randomized clinical trials amongst out‐patients attending a medical oncology clinic
Authors: Ellis Peter M. , Dowsett Sharon M. , Butow Phyllis N. , Tattersall Martin H.N.
Published: March 2003

Objective To assess the understanding of and attitudes towards randomized clinical trials amongst patients attending oncology out‐patient clinics.

Design Cross‐sectional survey.

Subjects Patients attending medical oncology out‐patient clinics at a Sydney teaching hospital.

Main outcome Patients' willingness to participate in a randomized clinical trial.

Results Sixty consecutive patients were surveyed. The mean age was 55.2 (SD 14) years. Eighty‐eight per cent of respondents thought that patients should be asked to participate in trials testing new treatments, however, only a third would consider participating in a randomized trial themselves. If a trial was endorsed by an independent cancer information service such as the NSW Cancer Council, 72% of respondents would be more likely to participate. Knowledge about randomized trials was not high. Respondents scored a median of 3 out of 7 (interquartile range, 2–4) correct answers to a series of questions about randomized trials. Patients willing to participate in a randomized trial were more likely to perceive the doctor favourably (P = 0.05), less likely to perceive trials as experimental (P = 0.05) and less likely to perceive trials as representing an inconvenience or loss of control (P = 0.09).

Conclusions Understanding amongst patients of the need for and mechanisms of randomized clinical trials is not good. This may contribute to the difficulties investigators face in seeking consent for clinical trials. Evaluation of new strategies to educate the public and patients about randomized trials is needed. Involvement of consumers in the design and conduct of clinical trials and evaluation of strategies to improve doctors' communication of clinical trial information is also required.