bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary soy oil content and soy‐derived phytoestrogen genistein increase resistance to alopecia areata onset in C3H/HeJ mice
Authors: McElwee K. J. , Niiyama S. , Freyschmidt‐Paul P. , Wenzel E. , Kissling S. , Sundberg J. P. , Hoffmann R.
Published: December 2003

Abstract: Alopecia areata (AA) is a complex, multi‐factorial disease where genes and the environment may affect susceptibility and severity. Diet is an environmental factor with the potential to influence disease susceptibility. We considered dietary soy (soya) oil content and the soy‐derived phytoestrogen genistein as potential modifying agents for C3H/HeJ mouse AA. Normal haired C3H/HeJ mice were grafted with skin from spontaneous AA affected mice, a method previously shown to induce AA. Grafted mice were given one of three diets containing 1%, 5% or 20% soy oil and observed for AA development. In a separate study, mice on a 1% soy oil diet were injected with 1 mg of genistein three times per week for 10 weeks or received the vehicle as a control. Of mice on 1%, 5%, and 20% soy oil diets, 43 of 50 mice (86%), 11 of 28 mice (39%), and 2 of 11 mice (18%) developed AA, respectively. Four of 10 mice injected with genistein and 9 of 10 controls developed AA. Mice with AA had hair follicle inflammation consistent with observations for spontaneous mouse AA, but no significant association was observed between the extent of hair loss and diet or genistein injection. Mice that failed to develop AA typically regrew white hair from their skin grafts associated with a moderate macrophage and dendritic cell infiltration. Soy oil and derivatives have previously been reported to modify inflammatory conditions. Hypothetically, soy oil compounds may act on C3H/HeJ mice through modulating estrogen‐dependent mechanisms and/or inflammatory activity to modify AA susceptibility.
Mast cell survival and apoptosis in organ‐cultured human skin
Authors: Kivinen Petri K. , Nilsson Gunnar , Naukkarinen Anita , Harvima Ilkka T.
Published: December 2003

Abstract: Mast cells accumulate and persist predominantly in the upper dermis of the skin but the mechanism for this is obscure. The skin is normally exposed to external air, which is essential for the maturation of the epidermis and probably also the dermis. In order to clarify the importance of air exposure on dermal mast cells, skin organ culture at the air–liquid interface (ALI) and submerged (SM) in medium (10% fetal calf serum and Dulbecco's modification of Eagle's medium) was used to study changes in tryptase‐, chymase‐ and Kit‐positive mast cell numbers during cultivation for up to 14 days. In addition, possible apoptosis (TACS TdT in situ apoptosis detection method) in chymase‐positive mast cells was studied during the culture. In the less‐physiologic SM culture, the number of Kit‐positive mast cells decreased rapidly on day 1–2 and tryptase‐positive cells decreased markedly on day 14. This decrease in mast cell numbers can be explained by the finding that a rapid increase in the apoptosis index of mast cells was induced on day 1–2. In contrast, in the more physiologic ALI culture, the number of Kit‐positive cells was sustained over 1–2 days but then decreased on day 7. In addition, tryptase‐positive cells decreased steadily in number but not to the same extent as those in the SM culture. Moreover, the increase in the apoptosis index of mast cells was delayed until day 7 in the ALI culture. Addition of exogenous stem cell factor (up to 200 ng/ml) to the SM culture could not prevent the decay in tryptase‐ and chymase‐positive cells. However, stem cell factor reduced significantly the number of Kit‐positive cells already on day 2 indicating that the cells had responded. Addition of histamine (0.25 or 1 mM) or tumor necrosis factor‐α (500 or 2000 U/ml) caused a decrease in the number of tryptase‐ and Kit‐positive cells in the SM culture. In conclusion, a novel finding was that air exposure in the ALI culture markedly delayed the rapid apoptosis and subsequent decrease in mast cell numbers noted to occur in the SM culture. Stem cell factor could not prevent the rapid decrease in mast cell numbers. Histamine and tumor necrosis factor‐α are possible factors promoting the decline in mast cells.
Tyrosine hydroxylase isoenzyme I is present in human melanosomes: a possible novel function in pigmentation
Authors: Marles Lee K. , Peters Eva M. , Tobin Desmond J. , Hibberts Nigel A. , Schallreuter Karin U.
Published: December 2003

Abstract: Both human epidermal melanocytes and keratinocytes have the full capacity for de novo synthesis of 6(R) L‐erythro 5,6,7,8, tetrahydrobiopterin, the essential cofactor for the rate limiting step in catecholamine synthesis, via tyrosine hydroxylase. Catecholamine synthesis has been demonstrated in proliferating keratinocytes of the epidermis in human skin. This study presented herein identified for the first time the expression of tyrosine hydroxylase isozyme I mRNA within the melanocyte. The location of the enzyme was demonstrated in both the cytosol and melanosomes of human epidermal melanocytes, using immunohistochemistry and immunofluorescence double staining as well as immunogold electron microscopy. High‐performance liquid chromatography (HPLC) analysis of pure melanosomal extracts from the human melanoma cell line, FM94, confirmed the production of L‐dopa within these organelles. In addition, enzyme activities for both tyrosine hydroxylase and tyrosinase were measured in the same preparations, by following the catalytic release of tritiated water from L‐[3,5‐3H]tyrosine. The melanosomal membrane location of tyrosine hydroxylase together with tyrosinase implies a coupled interaction, where L‐dopa production facilitates the activation of tyrosinase. Our results support a direct function for tyrosine hydroxylase in the melanosome via a concerted action with tyrosinase to promote pigmentation.
Epidermolysis bullosa simplex keratinocytes with extended lifespan established by ectopic expression of telomerase
Authors: Jensen Thomas G. , Sørensen Charlotte B. , Jensen Uffe B. , Bolund Lars
Published: December 2003

Abstract: As part of a strategy to develop somatic gene therapy of epidermolysis bullosa simplex (EBS) we have established patient keratinocytes with expanded lifespan by ectopic expression of the human telomerase gene (hTert). The presence of an active telomerase enzyme was demonstrated by the telomerase repeat amplification protocol (TRAP). The hTert(+) cells have a normal karyotype and the cells have, until now, undergone more than 80 population doublings (PDs) after hTert retroviral transduction while control cells exhibited senescence‐associated proliferation arrest after 8 PDs. In organotypic culture the hTert(+) cells are capable of forming a stratified epidermis illustrating their preserved ability to differentiate.
A high frequency of allergen‐specific  CD8+ Tc1 cells is associated with the murine immune response to the contact sensitizer trinitrophenyl
Authors: Martin Stefan , Delattre Virginie , Leicht Cornelia , Weltzien Hans‐Ulrich , Simon Jan C.
Published: December 2003

Abstract: Chemical haptens induce a variety of allergic immune reactions by induction of hapten‐specific T cells. Contact sensitizers such as the hapten trinitrochlorobenzene (TNCB) elicit an allergic response, which is confined to the area of antigen exposure. Despite this localized allergic response, we show here that the trinitrophenyl (TNP)‐specific immune response is characterized by a rapid induction of CD8+ Tc1 type cytotoxic effector cells already after a single allergen contact which can be detected in all secondary lymphoid organs tested. We furthermore demonstrate that the rapid induction of CD8+ Tc1 effector cells correlates with an unusually high frequency of polyclonal TNP‐specific CD8+ effector T cells with specificities for a variety of MHC class I binding TNP‐peptides carrying the hapten in different positions. These data suggest that allergies to chemical haptens may in part be due to an unusually high frequency of polyclonal, allergen‐specific effector cells which are detected in all secondary lymphoid organs.
In vitroeffects of cisapride, metoclopramide and bethanechol on smooth muscle preparations from abomasal antrum and duodenum of dairy cows
Authors: Michel A. , Mevissen M. , Burkhardt H. W. , Steiner A.
Published: December 2003

The objective of this study was to investigate the effects of cisapride (CIS), metoclopramide (MET) and bethanechol (BET) on contractility parameters from smooth muscle preparations of the abomasal antrum and proximal duodenum of cows. Smooth muscle preparations were harvested shortly post‐mortem from 42 healthy dairy cows, and concentration–response curves were performed by cumulative application of the drugs. Cisapride and MET did not have any significant effect on the contractility parameters studied, while BET induced a significant, concentration‐dependent increase in basal tone (BT), mean amplitude (Amean), and area under the curve (AUC) in smooth muscle preparations from the abomasal antrum, but not from the duodenum. The effect of BET on BT was more pronounced in specimens with longitudinal orientation while the maximal obtainable effect (Vm) inAmeanwas more pronounced in circular‐oriented preparations. Atropine (1 × 10−5 m) significantly inhibited the effect of BET, whereas pre‐incubation with hexamethonium or tetrodotoxin (TTX) had no effect, suggesting that the effect was mediated by cholinergic receptors on the smooth muscle. The results may be relevant to diseases or disorders associated with gastric emptying and gastric hypomotility. Further investigations are warranted to investigate the potential ability of BET to enhance abomasal emptying of adult dairy cows.
Intramuscular dosing strategy for ampicillin sodium in horses, based on its distribution into tissue chambers before and after induction of inflammation
Authors: van den Hoven R. , Hierweck B. , Dobretsberger M. , Ensink J. M. , Meijer L. A.
Published: December 2003

The Pharmacokinetics (PK) and distribution into tissue chamber fluid (TCF) of intramuscularly (i.m.) administered ampicillin sodium were examined in horses in order to design adequate dosing strategies. Concentration–time curves of ampicillin in plasma and TCF were determined in six horses following administration of 15 mg/kg ampicillin sodium, before and after the induction of local inflammation with 0.5% carrageenan. The calculated parameters were used to simulate various dosage–dosing interval combinations. Ampicillin was absorbed very rapidly following i.m. administration. Plasma concentrations were maximual between 18 and 21 min after administration. None of the plasma PK parameters were affected significantly by local (TC) inflammation. Penetration of ampicillin into and elimination from the TCF were affected significantly by inflammation and the half‐life of elimination from the tissue fluidt1/2(d)was significantly shorter in inflammation. In the simulated dosage–dosing interval scenarios, only a dosage of 15 mg ampicillin/kg four times daily would successfully treat all ampicillin‐susceptible bacterial isolates in well vascularized tissues. However a dosage as low as 10 mg/kg twice daily, would, in theory, treat all ampicillin‐susceptible isolates in the inflamed poorly vascularized tissues. Decreasing the dosage results in loss of efficacy that cannot be completely compensated for by increasing the frequency of dosing.
A detailed assessment of the pattern of moxidectin tissue distribution after pour‐on treatment in calves
Authors: Sallovitz J. M. , Lifschitz A. , Imperiale F. , Virkel G. , Lanusse C.
Published: December 2003

The use of topical (pour‐on) administration of endectocide drugs in cattle has reached world‐wide acceptance. However, only limited information is available on the kinetic behaviour for topically administered moxidectin (MXD). To improve our understanding of the relationship between pharmacokinetics and efficacy for pour‐on preparations, MXD concentration profiles were measured in tissues of endo‐ and ectoparasites location over 35 days postadministration. MXD distribution to the fluid content and mucosal tissue of the abomasum and different intestinal sections (duodenum, ileum, caecum and colon) was assessed. The comparative patterns of MXD distribution to skin and hypodermic tissue from different anatomical sites (backline, rib cage, thigh and face) were also investigated following the pour‐on administration. Wide tissue distribution and long residence time characterized the kinetics of topically administered MXD. MXD was recovered between 1 and 35 days post‐treatment in all the tissues investigated. The highest MXD availabilities were observed in the skin layers at the site of administration (backline) and in the fat tissue. The fluid contents of different intestinal sections showed MXD concentrations higher than those measured in their respective mucosal tissues, particularly at day 1 post‐treatment. MXD concentrations in the skin (epidermis + dermis) were higher than those measured in the hypodermic tissue. Large differences in the availability of MXD in skin from different anatomical regions (backline > rib cage > thigh > face) were observed. The low plasma and the high skin availability indicate the formation of a skin depot of the drug, being released slowly to the plasma and reaching concentrations in systemic tissues (abomasal mucosa, lungs, etc.) similar to those measured after subcutaneous administration. These findings demonstrate that target parasites may be exposed to markedly different drug concentrations according to their location sites, which is particularly relevant for ectoparasites located in different anatomical regions. Knowledge of the tissue distribution of topically administered endectocides contributes to understand the differences observed in efficacy and/or persistence of activity and to optimize their use in cattle.
Oral treatment of acute myeloid leukaemia with etoposide, thioguanine, and idarubicin (ETI) in elderly patients: a prospective randomised comparison with intravenous cytarabine, idarubicin, and thioguanine in the second and third treatment cycle
Authors: Ruutu T. , Koivunen E. , Nousiainen T. , Pelliniemi T.‐T. , Almqvist A. , Anttila P. , Jantunen E. , Koistinen P. , Koponen A. , Mikkola M. , Oksanen K. , Pulli T. , Remes K. , Sarkkinen R. , Silvennoinen R. , Timonen T. , Vanhatalo S. , Elonen E. ,   Finnish Leukaemia Group
Published: December 2003

A randomised multicentre study was conducted among patients over 65 yr of age with newly diagnosed acute myeloid leukaemia (AML) to compare oral treatment with etoposide 80 mg/m2 and thioguanine 100 mg/m2 twice daily on 5 d and idarubicin 15 mg/m2 on 3 d (ETI) to a mainly i.v. combination of cytarabine 100 mg/m2 twice daily on 5 d, idarubicin 12 mg/m2 × 1 , and thioguanine (TAI). Ninety‐two patients were enrolled. Their median age was 72 yr, range 65–84 yr. Sixty‐five patients had de novo AML, 21 AML subsequent to myelodysplastic syndrome, and six treatment‐related AML. They received at first a 6‐d i.v. treatment with cytarabine and idarubicin. After the first treatment, 68 patients were randomised to receive two cycles of ETI (n = 36) or TAI (n = 32) and thereafter maintenance with mercaptopurine and methotrexate. Of the 92 patients, 52 (57%) achieved remission at some stage. The median survival was 10 months. There were no significant differences between the patients randomised to ETI or TAI in the remission rate (67% vs. 72%), survival (12 months from randomisation in both arms), event‐free survival or relapse rate. The patients randomised to receive ETI spent significantly fewer days at hospital during the two randomised cycles (20 vs. 41 d, P = 0.010), and they had fewer days with infusions, shorter neutropenias and thrombocytopenias and fewer and less severe infections. In conclusion, treatment with oral ETI resulted in a similar antileukaemic effect as obtained with mainly i.v. TAI, with less toxicity and reduced need for hospitalisation.
Significant co‐expression of WT1 and MDR1 genes in acute myeloid leukemia patients at diagnosis
Authors: Galimberti S. , Guerrini F. , Carulli G. , Fazzi R. , Palumbo G. A. , Morabito F. , Petrini M.
Published: December 2003

A high expression of Wilms’ tumor gene (WT1) in acute myeloid leukemia (AML) seems to correlate with a poor outcome and its increased levels can be predictive of an impending relapse. WT1 has been shown in vitro to interact with the promoter of the MDR1, a gene involved in the multidrug resistance phenomenon.

The aim of this study was to measure, by real‐time polymerase chain reaction, levels of WT1 and MDR1 expression, in order to find a possible association between these genes, in a series of 50 newly diagnosed AML cases. Twenty‐five percent of patients carried very high (>75° percentile) MDR1‐ and 23.3%WT1‐mRNA levels. Interestingly, high levels of WT1 were significantly correlated with correspondent high levels of MDR1 gene. Nevertheless, the co‐expression of these genes did not significantly influence the complete response rate to the induction therapy.

Reported data confirm the existence of a co‐expression of WT1 and MDR1 genes even in vivo; this may be relevant because one consequence could be the positive selection by chemotherapeutic regimens of cells with higher MDR1 levels already present before treatment. Thus, the association between these genes could suggest avoiding the use of drugs involved in the multidrug resistance (MDR) phenomenon in patients carrying high levels of WT1 at diagnosis.
A case of a long‐time survivor with chronic active Epstein–Barr virus infection
Authors: Takeoka Yasunobu , Nakao Yoshitaka , Ueda Misako , Koh Ki‐Ryang , Aoyama Yasutaka , Nakamae Hirohisa , Yamamura Ryousuke , Ohta Kensuke , Takubo Takayuki , Yamane Takahisa , Hino Masayuki , Tokura Yoshiki , Ishihara Shigehiko , Oshima Koichi , Kimura Hiroshi , Imashuku Shinsaku
Published: December 2003

Epstein–Barr virus (EBV) is associated with hypersensitivity to mosquito bites (HMB) and fatal EBV‐associated hemophagocytic syndrome (HPS). The prognosis of patients with chronic active EBV infection (CAEBV) is very poor. We report a rare case of an adult woman patient with a 28‐yr history of HMB, who developed EBV‐HPS. EBV genome was detected in the serum and peripheral blood lymphocytes. Clonal proliferation of EBV was demonstrated by Southern blot analysis using an EBV genome terminal‐repeat probe. This is a very rare case of a long‐term survivor with CAEBV. The patient was initially treated with immunochemotherapy and achieved complete remission. However, the patient immediately relapsed and underwent allogeneic bone marrow transplantation (BMT) from her HLA‐matched brother. Peripheral blood cell recovered well, and EBV genome disappeared from the peripheral blood. Allogeneic BMT may be effective in eradicating EBV‐HPS. Unfortunately, the patient died of graft vs. host disease on the 92nd day after BMT.
Dendritic cell recovery after allogeneic stem‐cell transplantation in acute leukemia: correlations with clinical and transplant characteristics
Authors: Porta Matteo Della , Rigolin Gian Matteo , Alessandrino Emilio Paolo , Maiocchi Mariangela , Malcovati Luca , Vanelli Laura , Baratè Claudia , Rumi Elisa , Ciccone Maria , Cuneo Antonio , Lazzarino Mario , Castoldi Gianluigi
Published: December 2003

We have analyzed the kinetics of reconstitution of circulating dendritic cell (DC) subsets (myeloid‐DC1 and lymphoid‐DC2) in 19 patients affected by acute leukemia undergoing allogeneic hematopoietic stem‐cell transplantation (HSCT). We have found that pretransplant DC1 and DC2 were lower in leukemic patients than in healthy subjects (P = 0.003 and P = 0.004, respectively) and that the number of DC2 (but not DC1) infused with the graft was higher in patients receiving peripheral blood stem cells (PBSC) (P = 0.03). Patients recovered to the pretransplant DC1 and DC2 levels within day +60; however, a normal DC1 number was reached on day +365, while DC2 remained lower than in controls up to 1 yr after transplant. DC1 reconstitution did not differ significantly between patients receiving bone marrow stem cells (BMSC) or PBSC, while patients receiving PBSC presented increased levels of DC2 on day +30 (P = 0.008) and +100 (P = 0.047) and a higher number of T lymphocytes and natural killer cells until day +365. The occurrence of graft vs. host disease (GVHD) was not influenced in our cases by DC1/DC2 graft composition, but patients with acute GVHD when compared with patients without acute GVHD presented a significantly less rapid DC recovery (DC1 P = 0.03, DC2 P = 0.009 on day +30, and DC1 P = 0.012, DC2 P = 0.006 on day +100). At the moment of relapse, a decrease of DC1/DC2 numbers was observed in four patients and the presence of two different DC populations one with a normal karyotype, and the other with the same cytogenetic abnormality as the malignant clone was detected by fluorescence in situ hybridization analysis. In conclusion, these observations suggest that in allogeneic HSCT recipients, DC recovery is a slow process possibly contributing to the high risk of infections in the post‐transplant period and is possibly influenced by the source of HSC, the occurrence of GVHD and relapse. Further studies are warranted to investigate the significance of DC reconstitution in the transplant setting.
A comparison of fluorine‐18 fluoro‐deoxyglucose PET and technetium‐99m sestamibi in assessing patients with multiple myeloma
Authors: Mileshkin L , Blum R , Seymour J. F , Patrikeos A , Hicks R. J , Prince H. M
Published: December 2003

Objective:  The extent of disease in patients with multiple myeloma or related conditions may be difficult to assess. In previous small studies, both FDG‐PET (PET) and Tc‐99m sestamibi scans (MIBI) have identified sites of occult disease in myeloma.

Methods:  We reviewed the results for patients at our institution who have undergone PET and/or MIBI scans to assess myeloma. Concordance between the scans, ability to identify otherwise occult disease and impact on patient management was assessed.

Results:  Thirty‐six patients had ≥1 PET scan, 56 had ≥1 MIBI scan and 23 had concurrent PET and MIBI scans. MIBI detected additional sites to skeletal survey in 38 of 56 (68%) cases. PET detected additional sites to skeletal survey in 18 of 36 (50%) cases. MIBI generally detected more disease sites than PET. PET and MIBI were concordant in eight of 23 (35%) cases. The percentage plasma cell infiltrate within the marrow correlated with the number of sites detected by MIBI, but not by PET. In 23 of 69 cases (33%), scan results impacted on management, particularly by upstaging disease at diagnosis and by recognising subsequent disease progression. The results were also helpful for evaluating the presence of ongoing disease activity in previously irradiated sites remaining abnormal on skeletal survey following treatment.

Conclusions:  MIBI and PET are useful additional diagnostic tools for detecting otherwise occult sites of myeloma. The use of MIBI PET should particularly be considered in the evaluation of a patient with an early‐stage plasma cell dyscrasia to exclude the presence of more extensive disease.
Defoliation pattern, foraging behaviour and diet selection by lactating dairy cows in response to sward height and herbage allowance of a ryegrass‐dominated pasture
Authors: Tharmaraj J. , Wales W. J. , Chapman D. F. , Egan A. R.
Published: December 2003

The effects of sward surface height (SSH) and daily herbage allowance (HA) on the defoliation pattern and grazing mechanics of early lactation dairy cows grazing on irrigated perennial ryegrass–white clover pasture were studied. The hypothesis tested was that SSH and HA affect intake and diet selection through their effects on the pattern of defoliation which is influenced by the resistance to prehension bites.

Factorial combinations of two initial SSH (14 and 28 cm) and two daily HA (35 and 70 kg DM cow−1 d−1) were examined in a replicated experiment. The peak longitudinal tensile force required to break the sward portion encompassed in a 100 cm2 area [bite fracture force (BFF100)] was measured as an index of the resistance to prehension.

The volume of herbage defoliated and herbage intake increased with SSH (P < 0·05) and HA (P < 0·01). Corresponding to an increase in HA from 35 to 70 kg DM cow−1 d−1, there was a proportional increase in the total defoliation area (TDA) and intake by 0·24 and 0·55 in the short sward compared with 0·16 and 0·32 in the tall sward respectively. The results of this experiment suggest that a consistent spatial pattern of reduction of the canopy exists during defoliation by cows and that the volume of sward canopy defoliated is the major variable affecting herbage intake.

The BFF increased down the sward profile at a rate that was higher (P < 0·05) for the taller sward than for the shorter sward. It is proposed that a relatively lower resistance to prehension in the short sward compared with the tall sward explains the greater proportionate increase in TDA and intake corresponding to an increase in HA. The rate at which BFF100 increases down the sward profile is suggested as a sward physical variable that can influence the defoliation process. The estimated time and energy costs of prehension bites are discussed in the context that larger bites are handled more efficiently than smaller bites.
Effects of polyethylene colour and thickness on grass silage quality
Authors: Snell H. G. J. , Oberndorfer C. , Lücke W. , Van den Weghe H. F. A.
Published: December 2003

The aim of the investigation was to determine the influence of variations in thickness and colour of agricultural plastic film on silage preservation conditions and grass silage quality. For this purpose, 30 cylindrical plastic containers (mini‐silos; 0·3 m3) were filled with chopped grass and covered with five films of different thickness and colour: 90 μm, white; 125 μm, green; 150 μm, black; 200 μm, green and 200 μm, white. Four replications of each film type were placed in the open air. Two replications were housed indoors and exposed to an ‘artificial sky’ in a test apparatus. The surface temperature of the films was found to be strongly dependent on film thickness and colour. Results of the chemical analysis of silages did not reveal any significant influence of the films. This was also the case when restricting the analysis to the uppermost silage layer. The results showed that under the conditions of this experiment, well preserved forage can be produced with films of differing colour, as well as of lesser thickness.
The effect of additives in silages of pure timothy and timothy mixed with red clover on chemical composition and in vitro rumen fermentation characteristics
Authors: Hetta M. , Cone J. W. , Gustavsson A.‐M. , Martinsson K.
Published: December 2003

The aim was to compare the effects of additives on direct cut silages of pure timothy and timothy mixed with tetraploid red clover. First and second growth cuts were ensiled during three consecutive years, 1994, 1995 and 1996, either without any additive or with the addition of formic acid, or lactic acid bacteria in combination with molasses. Effects of the additives on the degradation characteristics of the herbage and the silages were analysed using an automatic in vitro gas production (GP) technique. At the end of the in vitro procedures, organic matter and neutral‐detergent fibre (NDF) degradabilities were determined.

The tetraploid red clover persisted in the leys during the 3 years and was the dominant species at the second growth in the mixed leys. The herbage from the mixed crops had lower dry‐matter contents, higher crude protein concentrations and higher buffering capacity compared with the pure timothy at both cuts. In general, the additives reduced pH, and the concentrations of ammonium‐N and acetic acid in the silages. The treated silages had a more rapid faster GP in both crops.

The silages from the mixed crop benefited more from the additives compared with the grass silages. The additives affected the soluble fractions as well as the NDF degradability of the silages of the mixed crop more than those fractions of the grass silages. The addition of molasses in combination with a commercial inocula resulted in increased production of lactic acid and ethanol in silages from both crops. The silages without additives could not meet the requirements for good silages according to the standards of the Swedish dairy industry.
Continuous and rotational grazing of dairy cows – the interactions of grazing system with level of milk yield, sward height and concentrate level
Authors: Pulido R. G. , Leaver J. D.
Published: December 2003

An experiment was conducted to test the hypothesis that for cows with high levels of milk yield, rotational grazing produces higher milk yields than continuous grazing. The comparison of grazing systems was made at two levels of milk yield (initially 20·3 and 32·5 kg d−1), and interactions with sward height and concentrate level were also examined. The study used 48 multiparous Holstein Friesian cows over a period of 62 d. Mean milk yield, its persistency and composition, live weight, body condition score and liveweight gain were not significantly affected by grazing system at either level of milk yield. There were no significant interactions between grazing system and sward height or concentrate level for any milk production measurement. Mean estimated herbage and total dry matter (DM) intake (P < 0·01), grazing time (P < 0·05) and ruminating time (P < 0·01) were significantly greater on the continuous grazing system. The cows in the higher milk yield group and those grazed at the higher sward height had a significantly (P < 0·05) higher estimated daily herbage DM intake and rate of herbage intake on the continuous grazing system than those on the rotational grazing system. There was no evidence to support the hypothesis that rotational grazing systems support higher levels of milk production than continuous grazing for cows of high milk yield. The shorter grazing time on the rotational grazing system indicated that cows may anticipate the timing of the daily movement of the electric fence, and this reduces their time spent grazing residual herbage.
Forage quality of Trifolium repens L. × T. nigrescens Viv. hybrids
Authors: Marshall A. H. , Abberton M. T. , Williams T. A. , Michaelson‐Yeates T. P. T. , Powell H. G.
Published: December 2003

Interspecific hybridization with the close relative Trifolium nigrescens Viv. (Ball clover) is a possible strategy to increase the seed yield potential of white clover (T. repens L.). Fertile F1 plants have been used as the basis for several generations of backcrossing using T. repens as the recurrent parent. Forage quality of the parental species and backcross hybrids when grown in mixtures with perennial ryegrass (Lolium perenne L.) was compared in field plots over three harvest years. The dry‐matter digestibility (DMD) and crude protein (CP) concentration of the legume fraction was greater than that of perennial ryegrass, but the water‐soluble carbohydrate (WSC) concentration of the legume components was lower than that of perennial ryegrass. Differences in forage quality between T. repens and the backcross hybrids were relatively small. The WSC concentration of the backcrosses was less than T. repens but the CP concentration was greater. Significant differences in the forage quality of the companion grass were observed when grown with the parental species and the hybrids; however, these differences were attributed to the plots with T. nigrescens and the F1 plants, where the clover content was low. Few differences in the forage quality of the grass were measured when grown with T. repens and the backcross hybrids. The impact of these results on the use of these hybrids in cultivar development programmes is discussed.
Effects of feeding clover silages on feed intake, milk production and digestion in dairy cows
Authors: Bertilsson J. , Murphy M.
Published: December 2003

Silages were made from pure crops of perennial ryegrass, red clover and white clover over 2 years. In all but one case the silage was stored as bales. A silage additive specially adapted for bales (Kofasil UltraTM) was used for all silages and they were all of good hygienic quality. The additive contained sodium nitrite, hexamethylene, tetraamine sodium bensoate and sodium propionate. The silages were offered ad libitum, either pure or mixed [grass/clover 0·50/0·50 on a dry‐matter (DM) basis] with a fixed amount (8 kg) of concentrate. Two experiments, one in each year, were performed with high‐yielding multiparous dairy cows in mid‐lactation, and both rumen‐cannulated and intact cows were used. The experiments were carried out using an incomplete changeover design with fifteen cows and five treatments each year.

The cows consumed large quantities of these silages (12·7–16·3 kg DM per cow per day). The highest intakes were obtained when the red clover and the 0·50 red clover:0·50 perennial ryegrass silage diets were offered. However, there was a difference between years. In year 1, 0·50 red clover:0·50 perennial ryegrass and 0·50 white clover:0·50 perennial ryegrass silage diets showed the highest intakes while pure perennial ryegrass and white clover silage diets gave lower intakes. In year 2 the highest intake of silage was obtained when the diet containing silage from red clover from a second cut was offered, while the silage from red clover from a first cut gave the lowest intake. The voluntary intakes of silages from white clover and perennial ryegrass were intermediate. No cases of bloat or other digestive disturbances were observed. Milk yield was significantly lower for the perennial ryegrass silage diet compared with all other diets in year 1. In year 2 milk yield was highest for the white clover silage diets and lowest for the red clover silage diets from both cuts. In year 1 there were relatively small differences in milk composition while in year 2 milk fat content was significantly lower with white clover silage diet and milk protein content was significantly higher with the perennial ryegrass diet. The overall conclusion from these experiments was that cows were able to consume large quantities of pure legume silage without serious disturbance to their metabolism. Differences in measurements of rumen metabolism were found between diets and especially between years. Milk production differences appears to be coupled to both differences in rumen physical characteristics, such as passage rate and particle size as well as differences in volatile fatty acid production in the rumen.
Influence of cultivar and cutting date on the fatty acid composition of perennial ryegrass (Lolium perenne L.)
Authors: Elgersma A. , Ellen G. , van der Horst H. , Muuse B. G. , Boer H. , Tamminga S.
Published: December 2003

Two experiments were conducted to evaluate the effects of cultivar and season on the fatty acid (FA) composition of the lipids of perennial ryegrass (Lolium perenne L.). Eight diploid cultivars were cut at the same target yield of approximately 2000 kg dry matter ha−1 between mid‐June and mid‐September. Two cultivars (Barlet and Magella) were harvested during four 2‐week periods and six cultivars (AberGold, Respect, Agri, Herbie, Barezane and Barnhem; cultivars 1–6) during three periods. The concentrations of individual FA were determined by gas chromatography. Barlet had higher concentrations of linolenic acid (C18:3) than Magella, but lower concentrations of linoleic acid (C18:2). Cultivars 1–6 were more variable in their leaf blade and stem proportions than Barlet and Magella. Despite this, there was no difference between cultivars 1–6 in the FA composition of the herbage. On average 0·74 of the FA consisted of C18:3. Higher concentrations of total FA were found in mid‐summer than in early summer. This was related to a high leaf blade proportion in the herbage, indicating that the proportion of leaf and stem of the herbage probably had more effect on lipid concentrations than the season per se in this period. However, in late August and mid‐September, the total FA concentration declined whereas the leaf blade proportion increased. Therefore, in this period environmental factors appeared to have a modifying effect. As consistent differences in the concentration of C18:3 were found among cultivars Barlet and Magella throughout the season, these studies demonstrate opportunities to change the composition of ruminant products through the choice of cultivars of perennial ryegrass.
Multicentre study of fetal cardiac time intervals using magnetocardiography
Authors: Stinstra J. , Golbach E. , van Leeuwen P. , Lange S. , Menendez T. , Moshage W. , Schleussner E. , Kaehler C. , Horigome H. , Shigemitsu S. , Peters M.J.
Published: December 2003

Objective
A database with reference values of the durations of the various waveforms in a magnetocardiogram of fetuses in uncomplicated pregnancies is assessed. This database will be of help to discriminate between pathologic and healthy fetuses. A fetal magnetocardiogram is a recording of the magnetic field in a location near the maternal abdomen and reflects the electric activity within the fetal heart. It is a non‐invasive method, which can be used with nearly 100% reliability from the 20th week of gestation onward.

Design
Durations of the waveforms were assembled from averaged magnetocardiograms and statistically processed.

Setting
Fetal magnetocardiograms were measured with different magnetocardiographs. All measurements were carried out in magnetically shielded rooms.

Sample
Fetal magnetocardiograms were obtained for 582 healthy patients.

Method
The durations of the waveforms were extracted from fetal magnetocardiograms measured at the cooperating centres. The variables collected included the duration of the P‐wave, the PR interval, the PQ interval, the QRS complex, the QT interval and the T‐wave and QTc value. The results were compared with values extracted from electrocardiograms of fetuses measured via electrodes attached to the maternal abdomen, from electrocardiograms measured during labour using a scalp electrode, and from electrocardiograms recorded in newborns, that were found in the literature.

Main outcome measures
Values of the durations are given as a function of gestational age including the regression line as well as the bounds marking the 90%, 95% and 98% prediction interval.

Results
The durations of the P‐wave, the PR interval, the QRS complex, the QT interval and QTc value increase linearly with gestational age. The durations of the PQ interval and the T‐wave are independent of fetal age.

Conclusion
The values found agree with those found in the literature. The scatter of the data is wide due to the variation in normal physiology, the measuring system and signal processing and the subjectivity of the researcher. However, the system can define normal ranges and may be used in diagnosis.
An analysis of maternal and fetal hair lead levels
Authors: Black A.P. , Knight R. , Batty J. , Haswell S.J. , Lindow S.W.
Published: December 2003

Lead contamination of the environment is an important public health consideration. There is evidence of declining blood lead levels in Britain, however, there is still concern about chronic exposure of the fetus and young children to low levels of lead and the effect that this has on neurodevelopment. Hair lead levels have been found to correlate well with body lead contamination. This study is the first to document the level of hair lead in pregnant women and their babies from an urban British population. There was no evidence of toxic maternal lead levels and the fetus is protected by the placental barrier.
Interleukin‐1 receptor antagonist polymorphism in women with peritoneal adhesions
Authors: Wieser Fritz , Tempfer Clemens , Schneeberger Christian , van Trotsenburg Michael , Huber Johannes , Wenzl Rene
Published: December 2003

Interleukin (IL)‐1 has been shown to induce peritoneal adhesions. We determined the IL‐1 receptor antagonist (IL‐1RN) genotype with respect to the two most common variant alleles IL‐1RN*2 and IL‐1RN*3 in Caucasian women with peritoneal adhesions. One hundred seven women with surgically verified peritoneal adhesions and 79 controls without peritoneal adhesions served as controls. Univariate analysis showed an increased risk for peritoneal adhesions for Caucasian women carrying the mutant IL‐1RN*2 allele (OR: 2.1; 95% CI: 1.3–3.4; P= 0.004). Multiple logistic regression analysis demonstrated an increased risk for peritoneal adhesions, which is independent of previous abdominal surgery and endometriosis. Our data suggest that IL‐1RN*2 allele carriers have an increased risk for adhesion formation.
Cost effectiveness of pre‐operative gonadotrophin releasing analogues for women with uterine fibroids undergoing hysterectomy or myomectomy
Authors: Farquhar Cynthia , Brown Paul M. , Furness Sue
Published: December 2003

Objective
To conduct a cost effectiveness analysis of pre‐operative gonadotrophin releasing hormone agonists (GnRHa) in women with uterine fibroids undergoing hysterectomy or myomectomy.

Design
A cost effectiveness analysis using the effectiveness data from a systematic review of GnRHa.

Setting
Secondary care.

Sample
Women with uterine fibroids undergoing hysterectomy or myomectomy and women volunteers.

Methods
Effectiveness data were used from a systematic review to construct a model and to calculate the cost per surgical outcome avoided. In order to evaluate the value women place on the outcome, a willingness to pay analysis of women volunteers was undertaken.

Main outcome measures
(a) The cost of avoiding abdominal hysterectomy and the cost of avoiding a vertical incision at either hysterectomy or myomectomy; (b) The value that women place on avoiding abdominal hysterectomy and on avoiding a vertical incision at either hysterectomy or myomectomy. All costs are in NZ dollars.

Results
For hysterectomy, the additional cost of treatment with GnRHa was NZ$1190 per case. The cost of avoiding one abdominal procedure was NZ$4577 per case and the cost of avoiding one vertical incision was NZ$6263. For a myomectomy, the additional cost of treatment with GnRHa was NZ$1535 per case. The cost of avoiding one vertical incision was NZ$4651 per case. These costs exceeded the benefit women placed on the outcomes.

Conclusion
Although the pre‐operative use of GnRHa results in benefits which include less frequent abdominal incisions in the case of hysterectomy and less frequent vertical incisions in the case of myomectomy, the benefits do not justify the costs. This study highlights the importance of considering both the benefits and costs in health care decisions.
Uterine artery embolisation for symptomatic fibroids: clinical results in 400 women with imaging follow up
Authors: Walker W.J. , Pelage J.P.
Published: December 2003

Objective
To evaluate the mid‐term efficacy and complications of uterine artery embolisation in women with symptomatic fibroids. To assess reduction in uterine and dominant fibroid volumes using ultrasound and magnetic resonance imaging.

Design
Prospective observational single‐centre study.

Setting
A district general hospital in Surrey and a private hospital in London.

Methods
Four hundred consecutive women were treated between December 1996 and February 2001. Indications for treatment were menorrhagia, menstrual pain, abdominal swelling or bloating and other pressure effects. Uterine artery embolisation was performed using polyvinyl alcohol particles and platinum coils.

Main outcome measures
Imaging was performed before embolisation and at regular intervals thereafter. Clinical evaluation was made at regular intervals after embolisation to assess patient outcome.

Results
Bilateral uterine artery embolisation was achieved in 395 women, while 5 women had a unilateral procedure. With a mean clinical follow up of 16.7 months, menstrual bleeding was improved in 84% of women and menstrual pain was improved in 79%. Using ultrasound, the median uterine and dominant fibroid volumes before embolisation were 608 and 112 cc, respectively, and after embolisation 255 and 19 cc, respectively (P= .0001). Three (1%) infective complications requiring emergency hysterectomy occurred. Twenty‐three (6%) patients had clinical failure or recurrence. Of these, nine (2%) had a hysterectomy. Twenty‐six (7%) women had permanent amenorrhoea after embolisation including four patients under the age of 45 (2%). Of these, amenorrhea started between 4 and 18 months after embolisation, and only three had elevated follicle stimulating hormone levels when amenorrhea developed. Thirteen (4%) women had chronic vaginal discharge considered as a major irritant. Thirteen pregnancies occurred in 12 patients. Ninety‐seven percent of women were pleased with the outcome and would recommend this treatment to others.

Conclusions
Uterine artery embolisation is associated with a high clinical success rate and good fibroid volume reduction. Infective complications requiring hysterectomy, amenorrhoea under the age of 45 and chronic vaginal discharge may complicate the procedure.
Listening to patients with unexplained menstrual symptoms: what do they tell the gynaecologist?
Authors: Echlin Dawn , Garden Anne S. , Salmon Peter
Published: December 2003

Objectives
To describe how women present unexplained menstrual symptoms to gynaecologists; to find out whether presentation reflects how intense their symptoms feel or how much benefit they expect from gynaecological treatment; and to test the prediction that surgical treatment decisions are more likely to follow specific types of presentation.

Design
A cross sectional cohort study.

Setting
Gynaecological outpatient clinics in a teaching hospital.

Sample
Fifty‐nine patients, referred for menstrual problems, in whom investigations had excluded physical disease.

Methods
Patients indicated symptom intensity and expectations of treatment before consultation on self‐completed questionnaires. Audiotape recordings of consultations with the gynaecologist were transcribed and patients' use of specific communication strategies was coded according to a previously reported scheme.

Main outcome measures
Treatment decision was noted.

Results
In a third to a half of patients, presentation extended beyond symptom report to include catastrophisation about consequences of symptoms, reference to other individuals to substantiate the patient's problems, criticism of previous or possible future interventions or request for hysterectomy. Those with greatest expectations of gynaecological treatment were more likely to catastrophise and request hysterectomy. Those with most intense subjective symptoms were more likely to catastrophise, refer to other individuals and request hysterectomy, and these strategies were more likely to be followed by surgical treatment decisions.

Conclusions
Surgical treatment for unexplained menstrual problems is not driven by gynaecologists. Reduction in unnecessary hysterectomies will require training in communication skills that reflects the challenging nature of many patients' presentation in the gynaecology clinic.