bluuebunny/crossref_metadata_2025 huggingface dataset:
Interannual variability in net CO2 exchange of a native tallgrass prairie
Authors: Suyker Andrew E. , Verma Shashi B. , Burba George G.
Published: March 2003

Year‐round eddy covariance flux measurements were made in a native tallgrass prairie in north‐central Oklahoma, USA during 1997–2000 to quantify carbon exchange and its interannual variability. This prairie is dominated by warm season C4 grasses. The soil is a relatively shallow silty clay loam underlined with a heavy clay layer and a limestone bedrock. During the study period, the prairie was burned in the spring of each year, and was not grazed. In 1997 there was adequate soil moisture through the growing season, but 1998 had two extended periods of substantially low soil moisture (with concurrent high air temperatures and vapor pressure deficits), one early and one later in the growing season. There was also moisture stress in 1999, but it was less severe and occurred later in the season. The annual net ecosystem CO2 exchange, NEE (before including carbon loss during the burn) was 274, 46 and 124 g C m−2 yr−1 in 1997, 1998, and 1999, respectively (flux toward the surface is positive), and the associated variation seemed to mirror the severity of moisture stress. We also examined integrated values of NEE during different periods (e.g. day/night; growing season/senescence). Annually integrated carbon dioxide uptake during the daytime showed the greatest variability from year to year, and was primarily linked to the severity of moisture stress. Carbon loss during nighttime was a significant part of the annual daytime NEE, and was fairly stable from year to year. When carbon loss during the burn (estimated from pre‐ and post‐burn biomass samples) was incorporated in the annual NEE, the prairie was found to be approximately carbon neutral (i.e. net carbon uptake/release was near zero) in years with no moisture stress (1997) or with some stress late in the season (1999). During a year with severe moisture stress early in the season (1998), the prairie was a net source of carbon. It appears that moisture stress (severity as well as timing of occurrence) was a dominating factor regulating the annual carbon exchange of the prairie.
Temperate intercropping of cereals for forage: a review of the potential for growth and utilization with particular reference to the UK
Authors: Anil  , Park  , Phipps  , Miller
Published: March 2003

Cereals grown for forage are increasing in importance in the rations of ruminants in the UK and have the potential to supply high proportions of energy‐rich forage in their diets. However, such diets usually require some degree of protein supplementation. Crop mixtures, generally referred to as intercrops, have the potential to boost the forage protein content of diets as well as having a number of agronomic benefits. In this paper, the growth and utilization of annual intercrops is reviewed with particular reference, where feasible, to temperate regions. General agronomic and feeding issues associated with cereal intercrops are outlined together with the practicalities of field‐scale management of intercrops in highly mechanized systems. A number of cereal‐based intercrop combinations are also considered, concentrating specifically on their value for forage production. The future potential for different combinations is discussed and research recommendations made.
Chloris gayana cultivars: RAPD polymorphism and field performance under salinity
Authors: Pérez  , Bravo  , Ongaro  , Castagnaro  , Seffino L. García , Taleisnik
Published: March 2003

Variability in the response to salinity within Chloris gayana (Rhodes grass) germplasm was evaluated under field conditions, and random amplified polymorphic DNA (RAPD) markers were used to assess genetic relatedness among cultivars/accessions. RAPD analysis showed a clustering of cultivars of known relatedness: cv. Pioneer and accessions Local and Trancas (derived from an old Pioneer pasture established in saline soil) belonged to the same cluster, Katambora to another and tetraploid Boma and Callide could be further separated, Boma belonging to a fourth, distant cluster. Field experiments were laid out in two types of plots: control [with electrical conductivity of the saturation extract (EC) = 3·64 dS m−1] and saline (EC=13·10 dS m−1) and two experiments were carried out: one to evaluate the effects of salinity on emergence and establishment, and the other, with a uniform number of plants per plot, to evaluate yield under saline conditions. All cultivars/accessions had salinity‐associated decreases in dry‐matter (DM) production during the establishment phase. After this stage, 1‐year DM yield was similar in all cultivars within each salinity level and production in the saline plots was significantly lower than in controls only in cv. Callide and accession Trancas. Second‐year production in the non‐saline plots increased by 30% on average over the previous year, whereas an average 40% reduction was observed in the saline plots. Thus, salinity had a negative effect on Rhodes grass establishment and persistence. The cultivars could not be ranked unequivocally by production under saline conditions, but tetraploids Boma and Callide may be said to be less tolerant than the rest on the basis of an increased proportion of dead leaves and decreased number of stolons observed in the saline plot.
Chemical composition and nutritive value of leaves and stems of tropical weed Chromolaena odorata
Authors: Apori  , Long  , Castro  , Ørskov
Published: March 2003

Chromolaena odorata (Siam weed) has been classified as a weed plant in West Africa. Data from C. odorata foliage after 4, 6, 8, 10 and 12 weeks of regrowth showed that the leaf fraction had a crude protein content above 194 g kg–1 dry matter (DM) and an average leaf to stem ratio of 2·1:1. Chemical analysis of the leaf fraction of an 8‐week‐old regrowth indicated a high crude protein content (258 g kg–1 DM) and a high degradable nitrogen content (60·7 g N kg–1 digestible organic matter), but low neutral‐detergent fibre (331 g kg–1 DM), acid‐detergent lignin (53·1 g kg–1 DM), total extractable phenolic (37·1 g kg–1 DM), extractable tannin (0·72 absorbance at 550 nm) and extractable condensed tannin (1·4 g kg–1 DM) contents. In sacco degradability analysis of the 8‐week‐old regrowth leaf sample showed a high 48 h organic matter (935 g kg–1 DM) and crude protein (953 g kg–1 DM) degradability. The leaf sample had an organic matter degradability of 670 g kg–1 DM as estimated by cumulative gas production in vitro after 24 h incubation. There was little or no phenolic‐related antinutritive factors in C. odorata. Additionally, leaf samples had no effect on rumen protozoa activity estimated as the rate of [14C]leucine Selenomonas ruminantum bacterial protein breakdown. Data from this study suggest that C. odorata leaves are of high nutritive value and might have the potential to be used as a protein supplement to ruminants. There is need for further investigation to test whether C. odorata leaves may have any deleterious effect on the host animal.
Introduction of seasonal and spatial specification to grass production and grassland use in a dairy farm model
Authors: Berentsen  , Giesen  , Renkema
Published: March 2003

A linear programming model of a dairy farm, in which grass production and grassland use was originally modelled using one growing period and one area of land, is extended. To include seasonal and spatial elements of variation not allowed for in the original model, the model was modified to reflect three growing periods in the season and then to reflect management of two separate areas of land. The resulting three models were used to assess farm physical planning, economic results and nutrient balances for an average Dutch dairy farm in a situation without and with levies on nutrient surpluses. It is concluded that incorporating seasonal and spatial elements provides greater insight into grassland management. Seasonal model specification does not result in significant changes in farm physical planning, income and nutrient surpluses. Spatial specification has a larger impact if one of the two areas cannot be grazed by dairy cattle.
Post‐flowering tillering in contrasting light environments of two New Zealand perennial ryegrass cultivars with different perennation strategies
Authors: Bahmani I. , Varlet‐Grancher C. , Hazard L. , Matthew C. , Betin M. , Langlais A. , Lemaire G. , Thom E. R.
Published: March 2003

Post‐flowering tillering responses of ‘Ellett’ and ‘Grasslands Ruanui’ perennial ryegrass (Lolium perenne L.) cultivars after inflorescence production were studied at INRA, Lusignan in France, at near ambient light (absence of light competition, control treatment) and under shading (low‐light intensity and low red–far red ratio). A dense sward containing inflorescence bearing plants of both perennial ryegrass cultivars at ambient light was cut to a height of 50 mm above ground level after which the light treatments were imposed. Forty‐five days later, data were collected on the number of tillers per plant, the number of new tillers per original tiller and the dry weight of vegetative and reproductive tillers. Regardless of light treatment, cv. ‘Ellett’ had fewer tillers per plant, higher weight per tiller and a higher proportion of reproductive tillers than did cv. ‘Grasslands Ruanui’. Number of tillers per plant and number of new tillers per tiller were consistently reduced under shade compared with the control treatment for both cultivars. When shaded, weight of reproductive tillers of cvs ‘Ellett’ and ‘Grasslands Ruanui’ were 40% and 43%, respectively, less than the control, whereas vegetative tiller weight did not change. In addition, differences between cultivars in the tillering strategy after flowering seem to be unaffected by the light environment. Thus, field observations regarding tillering of cvs ‘Ellett’ and ‘Grasslands Ruanui’ were consistent with current results suggesting different grazing managements are needed after flowering to optimize the replacement of tillers for both cultivars.
Seasonal changes in the crude protein concentration of mixed swards of white clover/perennial ryegrass grown without fertilizer N in an organic farming system in the United Kingdom
Authors: Weller R. F. , Cooper A.
Published: March 2003

Changes in the crude protein (CP) concentration of white clover and perennial ryegrass herbage from a mixed sward were determined on six sampling dates from May to October in each of 2 years. The swards were grown without fertilizer N in an organic farming system and continuously grazed by dairy cows during the grazing season. The annual mean contents of white clover in the dry matter (DM) of the sward were 272·3 and 307·0 g kg−1 in Years 1 and 2. The mean CP concentrations of the white clover and perennial ryegrass herbage were 251·6 and 151·9 g kg−1 DM in Year 1 and 271·9 and 174·0 g kg−1 DM in Year 2 respectively. The CP concentration of the white clover increased significantly during the grazing season from 220·0 to 284·1 g kg−1 DM in Year 1 and from 269·0 to 315·5 g kg−1 DM in Year 2. In the perennial ryegrass herbage the CP concentration increased from 112·2 to 172·6 g kg−1 DM in Year 1 and from 142·7 to 239·5 g kg−1 DM in Year 2. The rate of increase during the season in the CP concentration of the perennial ryegrass herbage was similar to the rate of increase recorded in the white clover herbage.
Effect of early turnout to grass in spring on dairy cow performance
Authors: Sayers H. J. , Mayne C. S.
Published: March 2003

This experiment examined the effects of grazing severity and degree of silage restriction during early turnout of dairy cows to pasture in spring on animal performance. Forty late‐winter‐calving Holstein Friesian dairy cows were allocated to one of five treatments between 7 March and 17 April 1997. The treatments involved early turnout of cows to grass for 2 h per day at two residual sward heights and two silage allowances, plus a control treatment, in a randomized block design. Dairy cows on the control treatment remained indoors throughout the experiment and were offered grass silage ad libitum. Dairy cows on all treatments were also offered 6 kg d–1 of a concentrate on a flat‐rate basis, split equally between the morning and afternoon milkings. Offering cows access to pasture in early spring for 2 h per day resulted in increases in both milk (P < 0·001) and protein yield (P < 0·01). On average, over all grazing treatments, cows produced an additional 2·6 kg milk per day compared with the control treatment (28·5 vs. 25·9 kg d–1, s.e.m. 0·43). Furthermore, these increases in milk yield were obtained even when silage was restricted indoors (28·4 vs. 25·9 kg d–1) and cows grazed down to a residual sward height of 40 mm (28·1 vs. 25·9 kg d–1). Protein yield was higher (P < 0·01) with dairy cows grazing pasture compared with cows indoors (848 vs. 707 g d–1, s.e.m. 28·9). Silage intake was significantly (P < 0·001) reduced when cows were turned out to pasture. In conclusion, early turnout of dairy cows to pasture in spring for 2 h per day reduced silage intake and increased milk yield and protein yield relative to those fully housed and offered grass silage with a low level of concentrates.
The effect of stage of perennial ryegrass maturity at harvesting, fermentation characteristics and concentrate supplementation, on the quality and intake of grass silage by beef cattle
Authors: Dawson L. E. R. , Kirkland R. M. , Ferris C. P. , Steen R. W. J. , Kilpatrick D. J. , Gordon F. J.
Published: March 2003

Abstract Two experiments were carried out in consecutive years to examine the influence of cutting date and restricting fermentation by carboxylic acid treatment on the nutrient intake from grass silage by beef cattle. In year 1, four cutting dates during July and August after a primary growth harvest and, in year 2, five cutting dates of primary growth between mid‐May and early July were examined. Herbage was ensiled either untreated or treated with high levels of acid additive (‘Maxgrass’, mean 8·6 l t−1). Ninety‐six (year 1) or forty‐eight (year 2) continental cross steers were used in partially balanced changeover design experiments with each silage type either unsupplemented or supplemented with 4·5 (year 1) or 5·5 (year 2) kg concentrates head−1 d−1. Silage digestibility declined significantly between initial and final harvest dates (P < 0·001), whereas silage dry‐matter (DM) and digestible energy (DE) intakes were significantly higher in the initial compared with final harvest dates in both years of the study (P < 0·01). Similarly, silage DM and DE intakes, and total DM intakes, of acid‐treated and unsupplemented silages were greater than those of untreated and concentrate supplemented silages, respectively (P < 0·001). The results indicate that earlier cutting dates, and addition of acid to herbage before ensiling, can increase silage DM intake by beef cattle.
Laparoscopic management of an unsuspected unusual ovarian malignancy
Authors: Bevan  , Farthing
Published: March 2003

Design

Case report.

Method

A 32‐year‐old lady with a large complex ovarian cyst was treated by laparoscopic oöphorectomy. The cyst was removed intact, utilizing an impermeable bag retrieval system. The cyst proved to be malignant and laparoscopic surgical staging was performed as a second procedure.

Conclusion

The majority of ovarian cysts in younger women will be benign and should be removed laparoscopically to reduce morbidity. The routine use of an impermeable bag retrieval system reduces the risk of tumour spillage into the peritoneal cavity when unexpected malignancy occurs. We report the first instance of laparoscopic management of a malignant granulosa cell tumour found coincidentally in a dermoid cyst.
The incidence of entry‐related laparoscopic injuries in Finland
Authors: Härkki‐Sirén Päivi
Published: March 2003

Objective

To analyse entry‐related laparoscopic complications in Finland.

Subjects

Data from the Finnish Hospital Discharge Register and the National Patient Insurance Association were used.

Results

51 entry‐related laparoscopic injuries were reported from 1990 through 1996, accounting for 22% of all major laparoscopic complications, the incidence being 0.5/1000 procedures. Of the entry injuries, 57% were bowel injuries, 15% incisional hernias, 12% large‐vessel injuries, 10% small‐vessel injuries and 6% bladder injuries. Altogether, 92% of the complications were treated by laparotomy.

Conclusions

Laparoscopic procedures are associated with complications related to laparoscopic access and the operation itself. Safety guidelines should be followed during laparoscopic procedures to reduce the complication risk.
Scottish audit of ectopic pregnancy
Authors:   Scottish Laparoscopic Surgery Audit Group, Brechin Susan , Farquharson David M. , Hawthorn Robert , Davis Jonathon , Fisher Peter , Philips William , Lumsden Mary A.
Published: March 2003

Objective

To evaluate the use of laparoscopic procedures in the treatment of ectopic pregnancies by a cross‐section of gynaecologists in Scotland

Design

A prospective registration of cases of laparoscopically treated ectopic pregnancy by gynaecologists. Case‐note review was also performed in selected hospitals.

Setting

13 hospitals in seven Scottish Health Board areas.

Subjects

Women having laparoscopic treatment of ectopic pregnancy.

Results

Between April 1994 and March 1996, 85 ectopic pregnancies were treated laparoscopically. Contraindications for laparoscopic surgery were most commonly size of the ectopic gestation (53%), presence of intraperitoneal bleeding (42%) and tubal rupture (44%). Salpingotomy was performed in 16% overall with only 86% of consultants monitoring serial human chorionic gonadotrophin levels.

Conclusions

Laparoscopic treatment of ectopic pregnancies in Scotland is infrequent. Lack of availability of adequate equipment and trained staff was often quoted as the reason preventing surgeons from developing their skills in these techniques. Complication rates were low and patient satisfaction high.
Microwave endometrial ablation (MEATM): a safe technique? Complication data from a prospective series of 1400 cases
Authors: Parkin David E. ,   MEA Users' Group
Published: March 2003

Objective

To determine the safety of microwave endometrial ablation when used for the treatment of excessive menstrual loss.

Design

Prospective observational study of all microwave endometrial ablations, describing all the complications associated with this method.

Setting

A total of 13 gynaecological units in both teaching and general hospitals in the United Kingdom and Canada.

Results

In 1433 cases there was only one major complication, a small bowel burn, giving an incidence of 0.7/1000. There were few minor complications.

Conclusion

Microwave endometrial ablation appears to be safer than hysteroscopic methods of endometrial ablation.
Complications of laparoscopic hysterectomy: comparison of the first 250 cases with the second 250
Authors: Jones Robert A.
Published: March 2003

Objective

A comparison of the complications of the first and second halves of a series of 500 laparoscopic hysterectomies using a constant stapling technique.

Design

A prospective study of a series of patients followed by retrospective data analysis by the author and an independent audit.

Setting

Specialist gynaecological practice at two private hospitals.

Subjects

Patients presented randomly and were offered the procedure, unless preoperative assessment precluded the use of the technique because of anticipated technical difficulty. This would have been for example, on account of excessive uterine size, coincidental abdominoplasty, patient preference or invasive pelvic cancer. In these cases conventional abdominal hysterectomy was offered instead.

Results

The complication rates were reduced with the passage of time and increasing experience. This was despite more difficult procedures being undertaken and the inclusion of other procedures, such as bladder neck suspension, appendicectomy and laparoscopic repair of prolapse. My rates compared favourably with those in other published reports on laparoscopic hysterectomy.

Conclusion

A single operator has used a constant surgical stapling technique for laparoscopic hysterectomy over 7 years. There is demonstrated in the series a steady improvement in complication rates.
Accuracy of hysterosalpingography and hysteroscopy for diagnosis of intrauterine lesions in infertile patients in an assisted fertilization programme
Authors: Cunha‐Filho João S.L. , De Souza Carlos A. B. , Salazar Cristiano C. , Facin Andréa C. , Freitas Fernando M. , Passos Eduardo P.
Published: March 2003

Objective 

To determine the accuracy of hysterosalpingography compared with hysteroscopy for detection of intrauterine abnormalities in infertile patients.

Design 

Cross‐sectional study.

Setting 

University hospital.

Subjects 

296 women undergoing an assisted fertilization programme.

Intervention 

Patients Underwent to hysteroscopy and hysterosalpingography prior to intrauterine insemination or in vitro fertilization.

Main outcome measures 

Hysterosalpingographic and hysteroscopic findings.

Results 

Hysteroscopy proved satisfactory in 90.5% of cases. Of the patients, 121 (40.9%) had an abnormal hysteroscopic evaluation. The most prevalent hysteroscopic findings were: cervical stenosis (n = 28); chronic endometritis (n = 17); synechiae (n = 16); suspected endometrial hyperplasia (n = 14); polyps (n = 11); and myomas (n = 7). The comparison of hysteroscopic and hysterosalpingographic findings revealed a sensitivity of 75.21% and a specificity of 41.14% for hysterosalpingography; the positive and negative predictive values were 47% and 70.60%, respectively.

Conclusions 

Hysterosalpingography is not sufficiently accurate, with regard to specificity or sensitivity, for screening pathologies of the endometrial cavity in infertile patients. Hysteroscopy should be performed in all patients before IVF and artificial insemination.
Laparoscopic appearance of pelvic miliary schistosomiasis
Authors: Al‐Harbi Obaid , Rohilly Sami Al , Hashim Ibtihaj , Turkistani Adnan F. M. , Baez‐Giangreco Atilio , Al Tweijry Afaf
Published: March 2003

We report the laparoscopic finding of a pelvic schitosomiasis in a 29‐year‐old Saudi woman who had a diagnostic laparoscopy for primary infertility. We believe that this is the first report to show the natural nodular appearance of this disease, and may help in the differentiation from other pelvic lesions such as tuberculosis and malignancy. Histological examination of the biopsy of these nodules confirmed the diagnosis of schistosoma haematobium. Hence she referred to an assisted reproduction unit.
Comparing vaginal and coelioscopic total or subtotal hysterectomies: prospective multicentre study including 82 patients
Authors: Jugnet Nathalie , Cosson Michel , Wattiez Armand , Donnez Jacques , Buick Valerie , Mage Gerard , Querleu Demis
Published: March 2003

Three surgical units were involved in a prospective comparative study: the Pavillon Paul Gellé in Roubaix, France for vaginal hysterectomies; the Hôtel Dieu Polyclinic in Clermont‐Ferrand, France for total percoelioscopic hysterectomies; and the Saint‐Luc Clinic in Brussels, Belgium for subtotal percoelioscopic hysterectomies.

The inclusion criteria were age (38–55 years old), the patients were either not menopausal or else they had received alternative therapies for menopause, and had mild uterine pathology with or without castration signs, but without pelvic pain. The vaginal or coelioscopic approach had to be practicable. Those patients with psychiatric histories, or with prolapses or stress incontinence which demanded surgery were excluded. Contraindications to any of the approaches (uterine volume larger than umbilicus, major previous pelvic surgery, severe endometriosis and virginity) were also considered to be exclusion criteria. A total of 82 patients who had undergone 31 vaginal hysterectomies, 31 total coelioscopic hysterectomies and 20 subtotal coelioscopic hysterectomies were followed up 1 year after the operation.

The population characteristics in the three groups were similar. Operating times were 70.8 min for vaginal hysterectomies (VH), 67.6 min for total percoelioscopic hysterectomies (TPCH) and 111.5 min for subtotal percoelioscopic hysterectomies (SPCH). The mean hospital stay was comparable in the three groups. The mean uterine weight was 225 g for the VH group, 281 g for the TPCH and 206.5 g for the SPCH group (P was not significant). The pain evaluation scales used by the patients during their hospital stay did not show any significant difference between the three groups. The mean times before patients could walk, return to work or resume sexual intercourse showed no significant differences between the groups. Mild urinary signs were reported in the mid‐term without any significant difference. Physical activity improved in 38.7% of the patients who had undergone VH, in 46.6% who had undergone TPCH and in 60% who had undergone SPCH (P not significant). Those patients who had undergone SPCH resumed satisfactory sexual intercourse significantly earlier (P = 0.0002). Intercourse was not significantly modified in the three groups. Quality of life was generally and significantly improved for 80.6%, 96.5% and 70%, respectively, of the patients in the VH, TPCH and SPCH groups.

Although some surgical teams are still reluctant to practise coelioscopic hysterectomies, all three hysterectomy types were finally demonstrated to be equivalent in this study. They were proved to be feasible even in patients with a large uterus. Operating times are no longer unfavourable factors when coelioscopies are performed by highly skilled surgeons.
Mesh erosion into the bladder following laparoscopic colposuspension
Authors: Paley Judith , Doyle Mark , Parr Nigel
Published: March 2003

A previously unreported finding of polypropylene mesh erosion into the bladder two years after laparoscopic colposuspension.

As with the vagina, synthetic mesh can erode into the bladder following urogynaecological sling procedures. Previous surgery may be a risk factor. Recurrent urinary tract infection or persistent haematuria following such a procedure should raise suspicion of mesh erosion.
Transcervical endometrial resection in 197 women. Hysterectomy rate and associated risk factors after a 5–8‐year follow‐up period
Authors: Panoskaltsis Theodore A. , Bassett Paul A. , Frappell Jonathan M.
Published: March 2003

Objective To identify the hysterectomy rate and associated factors following transcervical resection of the endometrium (TCRE).

Design Prospective observational study over an 8‐year period.

Setting Endoscopic Unit and Medical Audit Department, Derriford Hospital, Plymouth, UK.

Sample The first 197 women to undergo TCRE for menstrual disorders under the care of the senior author (J.M.F.).

Interventions Hysteroscopic endometrial resection and rollerball ablation.

Main outcome measure Hysterectomy rate.

Results All women were followed up from a minimum of 5 to a maximum of 8 years. The mean age was 41 years (range 24–56). The procedure was abandoned in three cases. There were no deaths. Immediate complications occurred in 5% of patients (including five uterine perforations and one case of deep venous thrombosis). No serious fluid overload sequelae occurred. There was one case of atypical endometrial hyperplasia, but no cancer was found. At the end of the study (median follow up of 72 months), survival analysis showed that the hysterectomy rate because of persistent menstrual complaints was 25%. Five hysterectomies were done because of uterine perforation at the time of TCRE and four for unrelated reasons. Multivariate analysis identified only blood loss at TCRE as an independent risk factor for hysterectomy. Other operative variables (age, surgeon, size of uterus, presence of fibroids, volume of glycine used, operating time, synchronous laparoscopic sterilization, and repeat TCRE) had no effect on the hysterectomy risk.

Conclusions Our results indicate that women who are offered a TCRE should be warned that they have a one‐in‐four risk of subsequently having a hysterectomy for persistent menstrual complaints. However, TCRE is a quick, safe operation with minimal operative morbidity. A repeat TCRE and the presence of fibroids did not increase the risk of hysterectomy in this group of women.
Low‐dose intermittent factor replacement for post‐operative haemostasis in haemophilia
Authors: Srivastava  , Chandy  , Sunderaj  , Lee  , Daniel  , Dennison  , Nair  , Mathews  , Anderson  , Nair  , Moses  , Sudarsanam
Published: March 2003

Recommendations for factor replacement therapy for postoperative haemostasis in haemophilia are often empirical and based on the physiological understanding of haemostatic requirements. This report describes the haemostatic management of patients with severe haemophilia undergoing major surgery using lower than usually recommended levels of factor replacement therapy. Eighteen adults (11 with FVIII and seven with FIX deficiency) with an average weight of 52 kg (range: 27–69) underwent 20 major surgical procedures. Factor concentrates were administered by intermittent bolus infusions. The dose of FVIII infused before surgery was 76 u kg−1 (range: 51–113) and that of FIX was 77 u kg−1 (range: 50–104). The preoperative levels achieved were 107% (range: 80–180) and 73% (range: 60–90), respectively. Between days 1 and 3 after surgery, an average of 29 u kg−1 day−1 (range: 20–46) of FVIII and 23 u kg−1 day−1 (range: 12–42) of FIX was used resulting in mean trough levels of 36% (range: 12–62) and 34% (range: 11–52), respectively. After day 4, an average of 19 u kg−1 day−1 (range: 15–25) of FVIII and 18 u kg−1 day−1 (range: 10–37) of FIX was administered until wound healing. The average duration of factor replacement was 11 days (range: 8–16). The mean dose of factor concentrate per patient was 260 u kg−1 (range: 179–338) of FVIII and 300 u kg−1 (range: 183–524) of FIX. The total amount of factor used per patient ranged from 12 380 to 19 980 units of FVIII and 8000 to 23 600 units of FIX. Only one patient had post‐operative bleeding which was due to a surgical cause. It is concluded that it may be possible to use much lower than recommended levels of factor replacement therapy for postoperative haemostasis in severe haemophilia.
Intraoperative transmission of blood‐borne disease in Haemophilia
Authors: Rodriguez‐Merchan
Published: March 2003

Because HIV and hepatitis B and C infection can be transmitted by exposure to infected blood or blood components, orthopaedists are at risk for HIV and hepatitis infection during surgical procedures. Thus, care must be taken to protect themselves from transmission of HIV and the hepatitis virus. The following precautions are recommended: double latex gloves, changed hourly, or a combination of cloth and latex gloves, enclosed hood and face‐masks and operative isolator with umbilical‐cord aspirator; knee‐length impermeable gowns of high‐count polyester weave or plastic‐lined nonwoven spun‐lace polyester; a combination of shoe‐covers that provide waterproof coverage as high as the knee; and disposable drapes.

If a member of the operating team is inadvertently pricked or cut, the wound should be washed immediately with iodine, soap and water. If the injured person has been immunized for the hepatitis B (and has adequate titres), or is positive for hepatitis B surface antigen or antibody, no further treatment is necessary. Otherwise, two doses of hepatitis B immune globulin should be given, 5 mL immediately and 5 mL after 1 month.

Because HIV infection can be transmitted by exposure to infected blood, orthopaedic surgeons are also at risk for HIV infection. Prospective studies suggest that this risk is very low; nevertheless, health‐care workers need to adhere rigorously to the aforementioned infection‐control precautions to minimize the risk of exposure to blood.
Laboratory and clinical markers of HIV infection in a national haemophilia cohort treated with recombinant factor VIII concentrate
Authors: Teitel J. M. , Card R. , Strawczynski H. ,   for the Association of Hemophilia Clinic Directors of Canada
Published: March 2003

Over an interval of approximately six months beginning in October 1993, most haemophilia A patients in Canada were switched from a plasma‐derived intermediate‐purity factor VIII concentrate (ipVIII) to a recombinant factor VIII (rVIII). In order to determine the consequence of this change in therapy on progression of HIV infection, we gathered surveillance data on clinical status and CD4 and CD8 cell counts in those patients who were HIV seropositive at the time of switching concentrates. Data were recorded at the time of switchover, annually for 2 years thereafter, and retrospectively at a point 1 year prior to the switch. CD4 cells fell significantly over the study period. Multiple direct comparisons revealed that this decline was restricted to the time intervals which included the final year in which patients received intermediate‐purity factor VIII concentrate (ipVIII). In the 2 year interval in which rVIII was used exclusively, there was a nonsignificant fall in CD4 cells. Changes in CD4 cells did not correlate with the intensity of exposure to either ipVIII or rVIII. CD8 cells did not fall significantly over the study period. There was no obvious reduction in the incidence of death or clinical progression over the 2 years in which rVIII was used. However, we are hopeful that the stabilizing trend in CD4 cell counts which followed the introduction of rVIII will be predictive of corresponding clinical stabilization over the coming years.
The determination of von Willebrand factor activity by collagen binding assay
Authors: Siekmann  , Turecek  , Schwarz
Published: March 2003

A new collagen binding assay has been developed for the determination of the functional activity of human von Willebrand factor based on the following principle: pepsin‐digested type III collagen from human placenta was covalently immobilized on a microtitre plate. Binding of collagen to the microtitre plate was carried out in neutral phosphate buffer within 1 h. A collagen concentration of 3 μg mL–1 was sufficient to achieve optimal coating. After drying, the coated microtitre plates remained stable for months without losing their vWF‐binding properties and could be incorporated into a ready‐to‐use kit. The suitability of various types of collagen for use in this assay was evaluated by simulating the binding of vWF to collagen immobilized on the microtitre plate by using surface plasmon resonance technology with collagen immobilized on a sensor chip. vWF was most effectively bound to pepsin‐digested type III collagen from human placenta. The assay thus comprises the following steps: (1) serial dilutions of a vWF reference preparation and vWF‐containing samples are prepared and bound to a microtitre plate which is precoated with collagen; (2) vWF is detected with a polyclonal antibody; (3) the substrate reaction is photometrically measured with an ELISA reader. This test is highly specific and sensitive for vWF (detection limit: 10 ng mL–1). The collagen binding activity measured corresponds to the degree of multimerization of vWF. The high sensitivity and the short time needed to carry it out may make it useful for clinical diagnosis and for the measurement of the functional activity of vWF in factor concentrates. In certain applications it may represent a suitable replacement for the ristocetin cofactor assay.
Management of haemophilia in the developing world
Authors: Lee C. A. , Kessler C. M. , Varon D. , Martinowitz U. , Heim M. , SRIVASTAVA A. , CHUANSUMRIT A. , CHANDY M. , DURAISWAMY G. , KARAGUS C.
Published: March 2003

Summary. The problems with management of haemophilia in developing countries are poor awareness, inadequate diagnostic facilities and scarce factor concentrates for therapy. The priorities in establishing services for haemophilia include training care providers, setting up care centres, initiating a registry, educating affected people and their families about the condition, providing low‐cost factor concentrates, improving social awareness and developing a comprehensive care team. A coagulation laboratory capable of reliably performing clotting times with correction studies using normal pooled, FVIII and FIX deficient patient plasma and factor assay is most essential for diagnosis. More advanced centralized laboratories are also needed. Molecular biology techniques for mutation detection and gene tracking should be established in each country for accurate carrier detection and antenatal diagnosis. Different models of haemophilia care exist. In India, there is no support from the government. Services, including import of factor concentrates, are organized by the haemophilia Federation of India, with support from other institutions. Haemophilia is managed with minimal replacement therapy (about 2000 i.u./PWH/year). In Malaysia, where the system is fully supported by the government, facilities are available at all public hospitals and moderate levels of factor concentrates are available ‘on‐demand” (about 11,000 i.u./PWH/year) at the hospitals. Haemophilia care in South Africa is provided through major public hospitals. Intermediate purity factor concentrates are locally produced (about 12,000 i.u./PWH/year) at low cost. The combined experience in the developing world in providing haemophilia services should be used to define standards for care and set achievable goals.
Treatment of von Willebrand disease
Authors: Lee C. A. , Kessler C. M. , Varon D. , Martinowitz U. , Heim M. , MANNUCCI P. M.
Published: March 2003

Summary. von Willebrand disease is the most frequent of inherited bleeding disorders (1:100 affected individuals in the general population). The aim of treatment is to correct the dual defects of haemostasis, i.e., abnormal coagulation expressed by low levels of factor VIII and abnormal platelet adhesion expressed by a prolonged bleeding time. There are two main options available for the management of von Willebrand disease: desmopressin and transfusion therapy with blood products. Desmopressin is the treatment of choice in patients with type 1 von Willebrand disease, who account for approximately 80% of cases. This pharmacological compound raises endogenous factor VIII and von Willebrand factors and thereby corrects the intrinsic coagulation defect and the prolonged bleeding time in most type 1 patients. In type 3 and in the majority of type 2 patients desmopressin is not effective, and it is necessary to resort to plasma concentrates containing factor VIII and von Willebrand factor. Treated with virucidal methods, these concentrates are effective and currently safe, but the bleeding time defect is not always corrected by them. Platelet concentrates or desmopressin can be used as adjunctive treatments when poor correction of the bleeding time after concentrates is associated with continued bleeding.
Treatment options for bleeding episodes in patients undergoing immune tolerance therapy
Authors: Manno
Published: March 2003

Inhibitors to factor VIII develop in 4–20% of haemophilia A patients, with the percentage rising to 52% in certain subpopulations. The management of inhibitor patients is directed toward stopping acute haemorrhages, providing short‐term haemostasis before and after surgery, and inducing immune tolerance to factor VIII (immune tolerance therapy or ITT). Several different protocols have been used for ITT, but they are all centred around ongoing exposure to high doses of factor VIII. High responders (those patients with a large increase in inhibitor level after exposure to factor VIII) are the prime candidates for ITT, but low responders may also benefit from this treatment. It is often necessary to treat bleeding episodes during ITT, because elimination of inhibitors may require many years of therapy. Treatment of haemorrhages in inhibitor patients is reviewed for both low and high responders during ITT and in the absence of ITT. The choice of clotting agent for inhibitor patients who have not yet responded to ITT depends on current and past inhibitor levels, the severity of the haemorrhage, the site of the haemorrhage or the setting in which it occurs (e.g. surgical), and the extent of inhibitor cross‐reactivity with porcine factor VIII. Patients with high‐titre inhibitors experiencing a critical haemorrhage are generally best managed with bypassing agents (AUTOPLEX® T or FEIBA® VH), porcine factor VIII or rFVIIa.
Human recombinant DNA‐derived antihaemophilic factor (factor VIII) in the treatment of haemophilia A: conclusions of a 5‐year study of home therapy
Authors: SEREMETIS  , LUSHER  , ABILDGAARD  , KASPER  , ALLRED  , HURST  ,   THE KOGENATE® STUDY GROUP
Published: March 2003

Fifty‐eight previously treated haemophilic subjects were treated exclusively with the recombinant FVIII (rFVIII‐KOGENATE®) produced by Bayer Corporation (Berkeley, CA) in an international multicentre prospective study of more than 5 years duration. Fifty‐four of the 58 had severe haemophilia (< 2% FVIII) and four had moderate haemophilia (2–5% FVIII); 23/58 (40%) were seropositive for HIV, while 35/58 (60%) were HIV seronegative. Patients were monitored for safety and efficacy over a median period of 4.7 years (range 0.9–5.9 years) and received 17 922 infusions totalling 25.7 million units of rFVIII. Of 7107 bleeding episodes reported in home diaries, 5831 (82%) required only one treatment with rVIII. Twenty‐five invasive surgical procedures in 17 patients, including eight joint replacements, were successfully accomplished and 13 serious bleeding episodes in eight patients were successfully treated. FVIII recovery performed on 885 occasions using 39 different lots of rFVIII showed mean incremental recovery of 2.48% IU−1 kg−1 (± 0.64). Adverse events were associated with 42 infusions (0.2%); none caused discontinuation of therapy. Immunological parameters remained stable in HIV‐seronegative subjects treated with rFVIII; a small decrease in CD4 counts was noted in HIV‐seropositive individuals (mean − 37.2 cells mm–3 yr−1). No de novo formation of inhibitors to FVIII was noted; and no clinical allergic reactions occurred to murine or hamster proteins. These conclusions from the longest monitored safety study ever performed for a haemophilia treatment product (with more than 5 years of observation) confirm previous interim study reports that rFVIII is well tolerated over the long‐term, has biological activity comparable to that of plasma‐derived FVIII, and is safe and efficacious for the treatment of haemophilia A.
Prenatal diagnosis of haemophilia
Authors: LJUNG R. C. R.
Published: March 2003

Genotype assessment based on direct identification of the pathogenic mutation in a chorionic villi sample obtained in the 11–12th gestational week is the most reliable method for prenatal diagnosis and should be used if available. Genetic linkage studies of polymorphisms should be the second choice in the assessment of carriers and in prenatal diagnosis. Carriers of haemophilia should be offered adequate psychosocial support before, during and after the prenatal diagnostic procedures.
Nasopharyngeal angiofibroma in a patient with haemophilia A: a bleeding tumour in a bleeding‐prone patient
Authors: Öztürk  , Haznedaroğlu  , Öztürk  , Özcebe  , Yücel  , Akyol
Published: March 2003

Nasopharyngeal angiofibroma is a highly vascular tumour which occurs almost exclusively in adolescent males. Although it is histologically benign, it may cause serious clinical problems because of its tendency to bleed profusely during surgery. This paper presents the first case of nasopharyngeal angiofibroma in a patient with haemophilia A, another well‐known disease of bleeding tendency. In this case the tumoural mass was surgically removed with effective factor VIII replacement without any bleeding complication.
German recommendations for immune tolerance therapy in type A haemophiliacs with antibodies
Authors: Brackmann  , Lenk  , Scharrer  , Auerswald  , Kreuz
Published: March 2003

Haemophilia A is the most common X‐chromosomal‐linked congenital bleeding disorder and is caused by decreased activity of blood coagulation factor VIII. Affected individuals develop a variable phenotype of haemorrhages, mainly into joints and muscles depending on the amount of the residual factor VIII. The exogenous factor VIII‐substitution by plasma‐derived or recombinant products are the only treatments either on demand or prophylactically. The most important complication of treatment is the development of inhibitors that affect about 20%–50% of the severe cases. These antibodies neutralize the therapeutic effect of factor VIII‐concentrates, leading to recurrent bleeding episodes, progredient joint damages and sometimes life‐threatening situations. The only chance for a complete and permanent eradication of the inhibitors in these patients is the induction of Immune‐Tolerance (ITT) to substituted factor VIII by the application of high‐doses of factor VIII. The treatment demands a strict compliance of the patient and a much higher effort of the physician, to non‐compared inhibitor patients. Requirements for a consistent realization of the ITT to increase the successful outcome was carried out by German Haemophilia Center Directors.
von Willebrand disease and bleeding in women
Authors: Ragni  , Bontempo  , Hassett A. Cortese
Published: March 2003

Menorrhagia is a common health problem in women, particularly those with bleeding disorders. Little is known about the course of menorrhagia or other bleeding symptoms in women with the most common congenital bleeding disorder, von Willebrand disease (vWD). We determined the prevalence of menorrhagia, bleeding symptoms and coagulation abnormalities associated with vWD, including factor VIII activity, von Willebrand factor (vWF) antigen, ristocetin cofactor and bleeding time (BT), on a cohort of 38 females with type 1 vWD referred for diagnosis and medical care. Menorrhagia was the most common bleeding symptom in females with vWD, occurring in 93.1% of adult women. Menorrhagia was also the most common initial bleeding symptom, occurring in 53.1% of adult women in all of whom it began at menarche, median 14 years of age. There was a delay from initial bleeding symptoms, at median age 12 years, to diagnosis, at median age 16 years, P=0.0049. Although 94% undergoing surgery had previous bleeding, a vWD diagnosis was known preoperatively in only 6.2%, resulting in potentially preventable bleeding. In summary, menorrhagia is the most common bleeding symptom in females with vWD and begins at menarche. Obtaining a personal and family bleeding history promotes early diagnosis, potentially prevents postoperative bleeding, and improves the health of women with vWD.
Fibrin glue and clinical impact on haemophilia care
Authors: Kavakli
Published: March 2003

Fibrin glues, a kind of biological sealant, have been used for enhancement of local haemostasis, tissue sealing and wound healing for haemophilia and similar disorders. Commercial viral‐inactivated fibrin glue products are available in Europe and have recently been approved in the USA. Using fibrin glue, hospitalization, medical cost, viral transmission risk and factor supplementation will be reduced. In the near future, the role of fibrin glues will be increased in the haemophilia field.