bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors contributing to the racial differences in prostate cancer mortality
Authors: Tewari Ashutosh , Horninger Wolfgang , Pelzer Alexandre E. , Demers Raymond , Crawford E. David , Gamito Eduard J. , Divine George , Johnson Christine Cole , Bartsch George , Menon Mani
Published: September 2005

OBJECTIVE

To analyse, in a retrospective cohort study, differences in rates of surgical treatment for prostate cancer between African‐Americans and White Americans, and to evaluate the extent to which these differences are associated with disparities in survival rates between these groups.

PATIENTS AND METHODS

Clinical, pathological, and demographic data from 4279 men diagnosed with clinically localized prostate cancer between 1980 and 1997 were used. The variables assessed included age, disease stage, tumour grade, comorbidities, treatment method, and socio‐economic status (SES). Kaplan‐Meier survival curves were generated and compared using log‐rank tests. The Cox proportional hazards method was used for analyses involving adjustments for potential confounding factors.

RESULTS

The surgical treatment rate was 17% for African‐American and 28% for White patients (P < 0.001). In those patients treated conservatively or by radiation therapy, both crude and cancer‐specific survival rates were lower for African‐Americans than for Whites (P < 0.001). However, for patients undergoing surgery, differences in survival between African‐Americans and Whites were not statistically significant. According to our models, SES explained 50% and surgical treatment rates ≈ 34% of the differences in survival between African‐Americans and Whites.

CONCLUSIONS

This analysis suggests that the lower prostate cancer survival rates for the African‐Americans in the present population can be largely explained by differences in SES and lower surgical treatment rates. Efforts to increase awareness of treatment options among African‐American patients may be a way of improving survival in this group.
Visual estimation of tumour extent is not an independent predictor of prostate specific antigen recurrence
Authors: Jones Timothy D. , Koch Michael O. , Lin Haiqun , Cheng Liang
Published: September 2005

OBJECTIVE

To analyse tumour extent as a predictor of cancer progression after radical prostatectomy (RP), using a multivariate Cox regression model, as several variables (e.g. Gleason grade and tumour stage) are well‐established prognostic factors in prostate cancer but it is uncertain if the visual estimation of tumour extent (percentage of carcinoma) is an independent predictor for prostate cancer recurrence.

PATIENTS AND METHODS

Tumour extent was estimated in the RP specimens from 504 men with clinically localized prostate cancer; clinical follow‐up data were available for 459 men. The mean (range) follow‐up was 44.3 (1.5–144) months. Cancer progression was defined by the development of biochemical recurrence, local recurrence, or distant metastasis. Multivariate analysis was used to assess tumour extent as a predictor of cancer progression.

RESULTS

Of the 459 patients, 157 had cancer progression; the mean tumour extent was 36% and 24% in those with and without cancer progression, respectively (P < 0.001). Univariate analysis showed a significant association between the visual estimation of tumour extent and tumour stage, Gleason grade, surgical margins, extraprostatic extension, seminal vesicle invasion, lymph node metastasis, and preoperative serum prostate‐specific antigen level (all P < 0.001). However, in a multivariate Cox regression model controlling for pathological stage, Gleason score, and surgical margin status, the visual estimation of tumour extent was no longer a significant predictor of cancer progression (P = 0.84).

CONCLUSION

The visual estimation of tumour extent was associated with various established prognostic factors for prostate cancer, and with cancer progression in a univariate analysis, but it was not a significant predictor of cancer progression in the multivariate analysis controlling for pathological stage, Gleason score, and surgical margin status.
Fluorescence in situ hybridization for detecting transitional cell carcinoma: implications for clinical practice
Authors: Laudadio Jennifer , Keane Thomas E. , Reeves Hugh M. , Savage Stephen J. , Hoda Rana S. , Lage Janice M. , Wolff Daynna J.
Published: September 2005

OBJECTIVE

To determine the diagnostic sensitivity of genetic studies using fluorescence in situ hybridization (FISH) for detecting both new and recurrent cases of transitional cell carcinoma (TCC) in a routine clinical practice setting, as bladder cancer has a significant risk of recurrence and progression to invasive disease and thus sensitive surveillance testing is very important.

PATIENTS AND METHODS

FISH was performed using the UroVysionTM kit (Vysis Inc., Downers Grove, IL, USA) Consecutive patients were assessed using FISH, both to evaluate those with a history of TCC or with suspicious symptoms, and the FISH results were compared with concurrent biopsy and cytological assessments.

RESULTS

In all, 521 consecutive FISH tests from 300 patients were evaluated; 47% had a history of bladder cancer and 53% had suspicious symptoms. Of the 521 FISH tests, 24% were positive; concurrent cytology was available for 84% of the FISH tests, with a concordance rate of 78% (6% were positive for both and 72% were negative by both tests). For the discordant cases, FISH was positive and cytology negative in 21% of cases, and cytology was positive with a negative FISH for 1%. In all, 99 FISH tests had concurrent biopsy data. Of the 44 cases histologically positive for TCC, 32 were FISH‐positive, resulting in an overall sensitivity (95% confidence interval) of 73 (60–88)%. FISH detected 95% of cases with high‐grade carcinoma, while only seven of these 17 were positive by concurrent cytological assessment. FISH detected 56% and cytology detected 32% of low‐grade lesions. FISH detected all nine new cases with positive histology. Overall, the specificity of FISH was 65 (53–78)%. Of 112 patients with previous TCC, 28 had a recurrence; 22 of these had positive FISH results.

CONCLUSION

FISH analysis has a high sensitivity for detecting new cases of TCC, as well as recurrences. From the present data FISH is considerably more sensitive and only slightly less specific than cytology in diagnosing TCC. Therefore, we recommend FISH as a useful initial diagnostic tool in patients suspected of both new and recurrent TCC.
Dementia with cerebrovascular disease: the benefits of early treatment
Authors: Schindler R. J.
Published: September 2005

Patients with vascular dementia (VaD) and Alzheimer's disease with cerebrovascular disease (AD + CVD) have dementia associated with underlying CVD. Although diagnosis of VaD is challenging, VaD is typically characterized by a stepwise progression of dementia that is closely associated with stroke and focal neurological findings, and a symptom profile that often includes executive dysfunction leading to decreased ability to perform instrumental activities of daily living (IADL). In contrast, AD + CVD patients typically present with progressive deterioration of cognition/memory that may also be influenced by concurrent cerebrovascular events. Early diagnosis and intervention are desirable to prevent further decline due to subsequent vascular events. Management of CVD can limit deterioration of cognitive symptoms in VaD patients, and treatment benefits with cholinesterase inhibitors may be realized as improvement above baseline levels in dementia symptoms. Results from a combined analysis of two 24‐week, placebo‐controlled clinical trials show that donepezil‐treated VaD patients improve in cognition, global function, and performance of IADL. In contrast, AD + CVD patients may continue to decline despite management of CVD, and treatment benefits should be recognized as initial improvements followed by stabilization or slowed decline of dementia symptoms over time. In post‐marketing studies, donepezil‐treated AD and AD + CVD patients show similar benefits in cognition, global function, and quality of life. The results of these studies support the use of donepezil in treatment of patients with VaD or AD + CVD.
Ultimate success in epilepsy – the patient's perspective
Authors: Sander J. W.
Published: September 2005

Most people with epilepsy can live outwardly normal lives, but fear about impending seizures, driving restrictions, lack of independence, employment and social problems, medication‐related adverse effects and the presence of cognitive or psychiatric complications are all concerns readily identified by affected individuals. While seizure control is the overriding goal of treatment, it is essential to realize the importance that patients place on other aspects of daily functioning. While many of the concerns identified by patients can only be managed by improved social support, others (e.g. neuropsychological impairment, medication‐related adverse events, cognitive impairment, sleep disturbance) may be amenable to therapy (if available) or to the selection of a more appropriate antiepileptic drug. Each antiepileptic drug has a unique pharmacodynamic and tolerability profile. Awareness by the treating clinician of the pharmacological profile of each drug may help to minimize unwanted treatment‐related effects and possibly improve the outcome of treatment from an epilepsy patient's perspective. Therefore, in order to achieve true treatment success, clinicians need to understand how individuals perceive their disorder and, where possible, address those factors that adversely affect patient quality of life. For the person with epilepsy, successful treatment involves beneficial effects on social, vocational and psychological function. This extends beyond seizure control to freedom from the fear associated with seizures, confidence in pharmacological therapy and improvements in health‐related quality of life.
Defining success in clinical trials – profiling pregabalin, the newest AED
Authors: Ryvlin P.
Published: September 2005

The efficacy and safety of pregabalin as adjunctive therapy for patients with partial epilepsy with or without secondary generalization has been established by four randomized, 12‐week, double‐blind, placebo‐controlled trials (n = 1396) and four long‐term open‐label studies (n = 1480). Patients in the three fixed‐dose trials were ≥12 years of age, had ≥6 partial seizures and no 4‐week seizure‐free period during the 8‐week baseline period. Seventy‐three per cent of patients were taking ≥2 concomitant antiepileptic drugs. Responder rates across the effective doses (150–600 mg/day) ranged from 14% to 51% and demonstrated a significant dose–response relationship. The most common adverse events were central nervous system related, generally mild or moderate, transient, and tended to be dose related. The fourth placebo‐controlled trial compared a fixed dose of pregabalin 600 mg/day with a flexible‐dose regimen (150–600 mg/day). Responder rates were greater for both the fixed dose (45.3%, P < 0.001) and flexible dose (31.3%, P < 0.001) when compared with placebo (11.0%). Compared with the fixed‐dose group, the flexible‐dose patients had a lower incidence of adverse events and study discontinuations. In long‐term open‐label trials, the efficacy of pregabalin was maintained with respect to 50% responder rates suggesting no obvious tolerance developing over 2 years. Seizure‐free rates were 8.9% and 5.8% for the last 6 months and 1 year of pregabalin treatment, respectively. Long‐term open‐label pregabalin treatment was well tolerated.
Epilepsy – success in clinical practice: translating trials to practice
Authors: Gilliam F. G.
Published: September 2005

Success in clinical practice results from the combination of a clinician's experience, an understanding of patient preferences and factors that influence patient perceptions, and careful interpretation of data from clinical trials. However, successful clinical trials fulfil rigid methodological requirements in order to provide a basis from which to evaluate the place of a drug within a therapeutic strategy. Their translation into practice is therefore complicated by an intrinsic tension between the requirements for scientific methods that minimize error, and the need for clinically relevant data. In practice, the clinician has the flexibility to individualize epilepsy management to maximize benefits and minimize adverse effects of antiepileptic drug (AED) therapy. AED adverse effects and psychiatric comorbidity, in particular depression, have a profound impact on subjective health status; systematic screening for these confounding variables can guide clinical management and optimize quality of life. In addition, patient preferences can be acknowledged in any management plan. To achieve success in clinical practice, we need to remember that the information gleaned from clinical trials provides only part of the picture and needs to be augmented by our clinical experience, patient assessment (including routine screening for adverse effects and depression) and patient preference.
Can removal of back teeth contribute to chronic earwax obstruction?
Authors: Fransman Denny
Published: September 2005

Impacted earwax is extremely common in people with learning disabilities. Although it is not a serious medical condition it causes a number of very unpleasant problems. These symptoms include discomfort in and around the ear, hearing loss, dizziness and noises in the ears. It also causes secondary problems with ear infections and hearing aid use. This paper reviews the clinical symptoms of impacted earwax and investigates possible causality. Evidence shows that people with learning disabilities are twice as likely to have impacted wax than the general population. The reason for this association is unclear. In the present study, the correlation between the occurrence of chronic wax obstruction and a reduced ability to chew due to the absence of back (molar) teeth was investigated. In the current pilot we have used clinical records to establish the presence of chronic wax obstruction and postal questionnaires to ascertain participants’ dental status. The results of this study show a positive relationship between chronic earwax obstruction and the absence of back (molar) teeth. These findings have significant implications and should be considered when planning the health care of people with learning disabilities.
XY females: revisiting the diagnosis
Authors: Minto Catherine L. , Crouch Naomi S. , Conway Gerard S. , Creighton Sarah M.
Published: September 2005

Objectives  To investigate the accuracy of assigned diagnosis in XY female intersex conditions.

Design  Cross sectional hospital case notes review.

Setting  Tertiary hospital multidisciplinary intersex clinic.

Sample  Forty‐six adult intersex women with a complete or mosaic XY karyotype.

Methods  All clinical features and investigation results were reviewed and a diagnosis was assigned. This was compared to the original diagnosis assigned.

Main outcome measures  Data collected included presentation, all investigations, subsequent clinical course and all treatments (medical and surgical). These data were employed to assign an up‐to‐date intersex diagnosis, which was compared with the recorded diagnosis in the hospital case notes. Diagnoses were then rated according to level of accuracy.

Results  The 47.8% patients had an accurate diagnosis, 32.6% of diagnoses were inaccurate and currently under review, 13% had a wrong diagnosis and 6.5% remain with an unknown aetiology for their XY intersex condition.

Conclusions  Diagnostic accuracy is assumed to be high when evaluating published work on these conditions; however, this study shows 52.1% of patients have unknown, inaccurate or wrong diagnoses. Assigning the wrong diagnosis may be harmful, for example, if it leads to irreversible virilising changes or development of a gonadal malignancy, and for all cases excludes accurate condition management and genetic counselling for both the patient and their immediate family.
One‐trocar salpingectomy for the treatment of tubal pregnancy: a ‘marionette‐like’ technique
Authors: Ghezzi Fabio , Cromi Antonella , Fasola Maddalena , Bolis Pierfrancesco
Published: September 2005

Laparoscopic salpingectomy for the treatment of tubal pregnancy has traditionally been performed with two ancillary trocars. We report a novel single‐port technique requiring only an umbilical operative laparoscope and a percutaneous midline suture, inserted with a straight needle, to retract the affected fallopian tube. A total of 10 ectopic pregnancies have been successfully treated with this approach. The procedure was not technically demanding and the operative time was comparable to that of standard laparoscopic methods. No intraoperative and postoperative complication occurred. Ancillary trocars were not necessary in any of these cases. Our results showed that one‐trocar salpingectomy is a feasible and safe technique.
Parallel vertical compression sutures: a technique to control bleeding from placenta praevia or accreta during caesarean section
Authors: Hwu Yuh‐Ming , Chen Chie‐Pein , Chen Hung‐Sheng , Su Tsung‐Hsien
Published: September 2005

Fourteen women with placenta praevia (including one who also had placenta accreta) undergoing caesarean section had massive bleeding after removal of the placenta. In order to preserve the uterus, two parallel vertical compression sutures were placed in the lower segment to compress the anterior and posterior walls of the lower uterine segment. The haemorrhage from the lower segment stopped immediately after the knots were tightened. All women later resumed normal menstrual flow with no apparent complications. Two of the 14 women had a spontaneous pregnancy one to two years after the operation. This parallel vertical compression suturing technique is simple, easy and effective for controlling bleeding in women with placenta praevia or accreta. We suggest that this technique be tried first before other more complex procedures are undertaken.
Marriage still protects pregnancy
Authors: Raatikainen Kaisa , Heiskanen Nonna , Heinonen Seppo
Published: September 2005

Objective  To assess the risk factors and outcome of pregnancy outside marriage in the 1990s, in conditions of a high percentage of extramarital pregnancies and high standard maternity care, used by the entire pregnant population.

Design  Hospital‐based cohort study.

Setting  A university‐teaching hospital in Finland.

Population  The 25,373 singleton pregnancies of known marital and cohabiting status.

Methods  Odds ratios (ORs) with 95% confidence intervals were calculated to estimate the effect of extramarital childbearing on pregnancy outcome. Multiple logistic regression analyses were conducted to control for confounding maternal risk factors.

Main outcome measures  Small‐for‐gestational age (SGA) infants, preterm birth (less than 37 completed weeks), low birthweight (LBW; under 2500 g).

Results  Of the study population, 67.5% were married and 32.5% were unmarried; 24.2% of all mothers were cohabiting. Unmarried status was strongly associated with social disadvantage and particular risk factors, specifically unemployment, smoking and previous pregnancy terminations, which in turn had an impact on obstetric outcome. There were significantly more SGA infants among unmarried mothers (P < 0.001), with an absolute difference of 45%; more preterm deliveries (P= 0.001), with an absolute difference of 17.5%; and more LBW infants (P < 0.001), with an absolute difference of 26%. The differences in adverse pregnancy outcomes between study groups (i) all unmarried women, (ii) cohabiting women and (iii) single women, remained significant after multivariate analysis at adjusted ORs of 1.11, 1.11 and 1.07 for SGA, 1.17, 1.15 and 1.21 for LBW and 1.15, 1.15 and 1.29 for the preterm births, respectively.

Conclusion  Even in the 1990s when cohabitation was already common, pregnancy outside marriage was associated with an overall 20% increase of adverse outcomes, and free maternity care did not overcome the difference.
Antral follicle count, anti‐mullerian hormone and inhibin B: predictors of ovarian response in assisted reproductive technology?
Authors: Muttukrishna S. , McGarrigle H. , Wakim R. , Khadum I. , Ranieri D.M. , Serhal P.
Published: September 2005

Objective  The objective of this study was to evaluate the relationship between anti‐mullerian hormone (AMH), inhibin B and antral follicle count (AFC) with ovarian response.

Design  Retrospective study.

Setting  Fertility unit.

Sample  AFC was recorded, and a serum sample obtained on day 3 from all patients undergoing in vitro fertilisation (IVF). Patients were given 300 IU/L recombinant follicle stimulating hormone (FSH; Gonal F). The following day blood samples were collected.

Methods  Serum samples were assayed for FSH, AMH and inhibin B using commercial immunoassay kits and oestradiol using an in house assay.

Main outcome measures  Response to gonadotrophin stimulation and the number of eggs collected.

Results  AFC was negatively correlated to age (r=−0.426, P < 0.001). Delta inhibin B (levels of inhibin B on day 4 minus day 3) had the best association to the number of eggs collected (r= 0.533, P < 0.001) followed by basal AMH (r= 0.51, P < 0.001) and AFC (r= 0.505, P < 0.001). The number of eggs fertilised was significantly associated with basal AMH (r= 0.592, P < 0.001) and inhibin B (r= 0.548, P < 0.001). AMH with a cutoff of 0.2 ng/mL had the best sensitivity (87%) and specificity (64%) in predicting poor response. A cumulative score using basal FSH, basal AMH, delta E2 (levels of oestradiol on day 4 minus day 3), delta inhibin B, AFC and age gives the best predictive statistics to identify poor responders with 87% sensitivity and 80% specificity and a positive likelihood ratio of 4.36.

Conclusion  Delta inhibin B had the best positive association with the number of eggs collected and basal AMH is the single best predictor of poor response. AFC has a significant association with the number of eggs collected and is predictive of clinical pregnancy. It is evident that a single parameter is of limited value in predicting ovarian response. However, we have demonstrated a cumulative score using all the above markers could be useful in predicting poor response.
Transabdominal cerclage: the significance of dual pathology and increased preterm delivery
Authors: Farquharson Roy G. , Topping Joanne , Quenby Siobhan M.
Published: September 2005

Transabdominal cerclage is a recognised treatment for cervical weakness with a history of recurrent mid‐trimester loss and a failed elective vaginal suture. The emergence of dual pathology, such as antiphospholipid syndrome and bacterial vaginosis, is associated with an increased risk of preterm delivery (RR 2.34, 95% CI 1.15–5.8). The first 40 cases are described where strict adherence to an investigation protocol and consistent treatment plan has been implemented.
Hormonal and sonographic assessment of ovarian reserve before and after laparoscopic ovarian drilling in polycystic ovary syndrome
Authors: Kandil Mohamed , Selim Maha
Published: September 2005

This prospective observational study aimed to assess ovarian reserve after three different methods for induction of ovulation in 60 women between 30 and 40 years old with polycystic ovary syndrome. Women were equally divided into three groups. Group I included women who responded to clomiphene citrate. Women enrolled in groups II and III were subjected to either unilateral or bilateral ovarian drilling, respectively. Ovarian reserve testing was performed once before and three months after treatment. Basal serum inhibin B level showed a significant decrease after bilateral drilling compared with predrilling level (53.8 ± 13.5 vs 46.3 ± 6.2 pg/mL; P= 0.031). The antral follicle counts and summed ovarian volume showed a significant decrease after bilateral drilling (16.5 ± 1.3 vs 14.9 ± 2.1; P= 0.007 and 11.5 ± 1.0 vs 10.3 ± 1.1/mm3; P= 0.001). We concluded that diminished ovarian reserve may occur after bilateral ovarian drilling but not after clomiphene citrate induction of ovulation or unilateral drilling.
Changes in booking body mass index over a decade: retrospective analysis from a Glasgow Maternity Hospital
Authors: Kanagalingam Malini G. , Forouhi Nita G. , Greer Ian A. , Sattar Naveed
Published: September 2005

Whether booking body mass index (BMI) in the UK is increasing is unknown but is of clinical interest since overweight or obese pregnant women face far greater risks of pregnancy complications including pre‐eclampsia and gestational diabetes. We examined booking BMI in 1990 and 2002/2004, of women with singleton pregnancies. Our analyses indicate an increase of 1 U in mean BMI over this period despite lower parity in recent years. When the model was adjusted for maternal age, parity, smoking status and deprivation category the mean BMI was 1.37 U higher in 2002/2004 than in 1990. More striking was the significant increase in the proportion of women who were obese (BMI ≥ 30 kg/m2) at booking—more than twofold higher in unadjusted analysis (18.9%vs 9.4%) rising to greater than threefold higher in multivariate analysis. These findings suggest that obesity‐related pregnancy complications are likely to increase with implications for both mother and child.
The C46T polymorphism of the coagulation factor XII gene and idiopathic recurrent miscarriage
Authors: Walch Katharina , Riener Eva‐Katrin , Tempfer Clemens B. , Endler Georg , Huber Johannes C. , Unfried Gertrud
Published: September 2005

Thrombophilia has been described to be involved in the pathogenesis of idiopathic recurrent miscarriage (IRM). We investigated the association between IRM and a C→T polymorphism at nucleotide 46 in the 5′‐untranslated region of the coagulation factor XII (FXII) gene. Two hundred and twelve women with a history of IRM and 149 healthy controls were tested by a mutagenically separated polymerase chain reaction assay (MS PCR). Allele and genotype frequencies were not significantly different between the study and the control groups. Our data suggest that the FXII gene is not a candidate gene for this condition.
A randomised controlled trial comparing two temporising management strategies, one with and one without plasma volume expansion, for severe and early onset pre‐eclampsia
Authors: Ganzevoort Wessel , Rep Annelies , Bonsel Gouke J. , Fetter Willem P.F. , van Sonderen Loekie , De Vries Johanna I.P. , Wolf Hans ,   for the PETRA investigators
Published: September 2005

Objectives  Plasma volume expansion may benefit both mother and child in the temporising management of severe and early onset hypertensive disorders of pregnancy.

Design  Randomised clinical trial.

Setting  Two university hospitals in Amsterdam, The Netherlands.

Population  Two hundred and sixteen patients with a gestational age between 24 and 34 completed weeks with severe pre‐eclampsia, haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome or severe fetal growth restriction (FGR) with pregnancy‐induced hypertension, admitted between 1 April 2000 and 31 May 2003.

Methods  One hundred and eleven patients were randomly allocated to the treatment group, (plasma volume expansion and a diastolic BP target of 85–95 mmHg) and 105 to the control group (intravenous fluid restriction and BP target of 95–105 mmHg).

Main outcome measures  Neonatal neurological development at term age (Prechtl score), perinatal death, neonatal morbidity and maternal morbidity.

Results  Baseline characteristics were comparable between groups. The median gestational age was 30 weeks. In the treatment group, patients received higher amounts of intravenous fluids (median 813 mL/day vs 14 mL/day; P < 0.001) with a concomitant decreased haemoglobin count (median −0.6 vs−0.2 mmol/L; P < 0.001). Neither neurological scores nor composite neonatal morbidity differed. A trend towards less prolongation of pregnancy (median 7.4 vs 11.5 days; P= 0.054) and more infants requiring oxygen treatment >21% (66 vs 46; P= 0.09) in the treatment group was observed. There was no difference in major maternal morbidity (total 11%), but there were more caesarean sections in the treatment group (98%vs 90%; P < 0.05).

Conclusion  The addition of plasma volume expansion in temporising treatment does not improve maternal or fetal outcome in women with early preterm hypertensive complications of pregnancy.
Bleeding profiles and effects on the endometrium for women using a novel combination of transdermal oestradiol and natural progesterone cream as part of a continuous combined hormone replacement regime
Authors: Vashisht Arvind , Wadsworth Fred , Carey Adam , Carey Beverley , Studd John
Published: September 2005

Objective  Many women are seeking alternatives to conventional forms of hormone replacement. This study evaluates the endometrial effects of natural progesterone cream used in conjunction with transdermal oestradiol.

Design  Open plan study conducted over 48 weeks.

Setting  Tertiary referral London teaching hospital.

Population  Women at least two years postmenopausal.

Methods  Women were recruited nationally. They applied 40 mg transdermal natural progesterone cream and 1 mg transdermal oestradiol daily.

Main outcome measures  Endometrial histology, assessed by pipelle endometrial biopsy, ultrasound assessment of endometrial thickness and bleeding diaries.

Results  Fifty‐four women were recruited of which 41 completed the study. Mean age was 57.4 years. Thirty‐two percent of women had evidence of inadequate endometrial opposition (proliferative or hyperplastic) at the end of 48 weeks. At baseline, women had a mean endometrial thickness of 3.3 mm, which had significantly thickened to a mean of 5.3 mm by 24 weeks (P < 0.001). By 48 weeks, there was significantly greater increase in endometrial thickness from baseline in those women who displayed inadequate endometrial opposition, compared with those women who had adequate endometrial opposition (P= 0.004). At 24 weeks, 48% of women had remained entirely amenorrhoeic. By the end of the study, 35% of women had been entirely amenorrhoeic and 50% had had either no bleeding or spotting alone. The number of bleeding episodes did not reduce with time.

Conclusions  The dose of natural progesterone cream in this study was insufficient to fully attenuate the mitogenic effect of oestrogen on the endometrium. We would not recommend this combination of hormones to be used by postmenopausal women.
Changes of plasma vascular endothelial growth factor level after uterine artery embolisation for leiomyomata
Authors: Takeda Takashi , Osuga Keigo , Morishige Ken‐ichirou , Tasaka Keiichi , Nakamura Hironobu , Murata Yuji
Published: September 2005

Uterine artery embolisation (UAE) has become an alternative treatment for symptomatic uterine leiomyomata. Most reports suggest that it is well tolerated and effective, although there have been no reports of studies of biological parameters after UAE. In this study, we analysed the plasma level of vascular endothelial growth factor (VEGF) and the pulsatility index (PI) of uterine arteries before and after UAE. The level of plasma VEGF increased significantly after UAE (on day 1 and day 3) and decreased on day 7, and then increased again on day 30. The level of VEGF reached a peak value within three days after UAE. A significant inverse correlation was found between uterine artery PI and the level of VEGF on day 30, suggesting that VEGF may have negative effect on the efficacy of treatment of uterine leiomyomata by UAE.
The future of prenatal diagnosis: rapid testing or full karyotype? An audit of chromosome abnormalities and pregnancy outcomes for women referred for Down's Syndrome testing
Authors: Ogilvie Caroline Mackie , Lashwood Alison , Chitty Lyn , Waters Jonathan J. , Scriven Paul N. , Flinter Frances
Published: September 2005

Objective  To assess the implications of a change in prenatal diagnosis policy from full karyotype analysis to rapid trisomy testing for women referred primarily for increased risk of Down's Syndrome.

Design  Retrospective collection and review of data.

Setting  The four London Regional Genetics Centres.

Population  Pregnant women (32,674) in the London area having invasive prenatal diagnosis during a six‐year three‐month period.

Methods  Abnormal karyotypes and total number of samples referred for raised maternal age, raised risk of Down's Syndrome following serum screening or maternal anxiety were collected. Abnormal karyotypes detected by molecular trisomy detection were removed, leaving cases with residual abnormal karyotypes. These were assessed for their clinical significance. Pregnancy outcomes were ascertained by reviewing patient notes or by contacting obstetricians or general practioners.

Main outcome measures  Proportion of prenatal samples with abnormal karyotypes that would not have been detected by rapid trisomy testing, and the outcome of those pregnancies with abnormal karyotypes.

Results  Results from 32,674 samples were identified, of which 24,891 (76.2%) were from women referred primarily for Down's Syndrome testing. There were 118/24,891 (0.47%) abnormal sex chromosome karyotypes. Of the samples with autosomal abnormalities that would not be detected by rapid trisomy testing, 153/24,891 (0.61%) were in pregnancies referred primarily for Down's Syndrome testing. Of these, 98 (0.39%) had a good prognosis (46/98 liveborn, 3/98 terminations, 1/98 intrauterine death, 1/98 miscarriage, 47/98 not ascertained); 37 (0.15%) had an uncertain prognosis (20/37 liveborn, 5/37 terminations; 12/37 not ascertained) and 18 (0.07%) had a poor prognosis (1/18 liveborn, 2/18 miscarriage, 11/18 terminations, 4/18 not ascertained).

Conclusions  For pregnant women with a raised risk of Down's Syndrome, a change of policy from full karyotype analysis to rapid trisomy testing would result in the failure to detect chromosome abnormalities likely to have serious clinical significance in approximately 0.06% (1 in 1659) cases. However, it should be noted that this figure may be higher (up to 0.12%; 1 in 833) if there were fetal abnormalities in some of the pregnancies in the uncertain prognosis group for which outcome information was not available.
Alterations of Steppe‐Like Grasslands in Eastern Europe: a Threat to Regional Biodiversity Hotspots
Authors: CREMENE CRISTINA , GROZA GHEORGHE , RAKOSY LASZLO , SCHILEYKO ANATOLI A. , BAUR ANETTE , ERHARDT ANDREAS , BAUR BRUNO
Published: September 2005

Abstract:  Recent changes in agriculture (intensification or abandonment) have resulted in a critical reduction of steppe‐like grasslands in Eastern Europe. These grasslands harbor an extraordinarily high diversity of plants and invertebrates, including endemics, and are considered refugia for numerous threatened open‐land species. We examined species richness, and abundance, proportion of open‐land, endemic and threatened vascular plants, gastropods, and diurnal and nocturnal Lepidoptera in six different vegetation types all originating from steppe‐like grasslands in Transylvania, Romania. Vegetation types included extensively grazed pastures (initial stage), three seral stages of succession (early stage of abandoned grassland, abandoned grassland with shrubs, and mature forest), and two human‐made grassland alterations, namely abandoned vineyards and Pinus plantations. A total of 852 species (291 vascular plants, 24 gastropods, 129 diurnal and 408 nocturnal Lepidoptera) were found in the 22 study sites. The four taxonomic groups differed in their response to the abandonment of steppe‐like grassland, except that species richness of plants and diurnal Lepidoptera were positively correlated. The complementarity of species composition increased with successional age in all taxonomic groups examined. The number of characteristic open‐land species decreased with successional age in plants and gastropods. All investigated vegetation types harbored threatened (red‐listed) species. Endemic species were found in all vegetation types except mature forests and Pinus plantations. All Transylvanian endemics and the majority of threatened species found were open‐land species. Extensively cultivated vineyards, which have been abandoned for two to three decades, also maintained high plant and invertebrate diversities, comparable to those of the corresponding stages of grassland succession. In contrast, Pinus plantations (a recent grassland alteration) have changed habitat quality and will have a devastating effect on the unique, indigenous diversity of these steppe‐like grasslands as soon as the canopy closes. To prevent losses of characteristic species, we suggest a rotational grassland management program that maintains different seral stages. Succession to mature forest and additional Pinus plantations should be prevented.
Forest Stand Dynamics and Livestock Grazing in Historical Context
Authors: BORMAN MICHAEL M.
Published: September 2005

Abstract:  Livestock grazing has been implicated as a cause of the unhealthy condition of ponderosa pine forest stands in the western United States. An evaluation of livestock grazing impacts on natural resources requires an understanding of the context in which grazing occurred. Context should include timing of grazing, duration of grazing, intensity of grazing, and species of grazing animal. Historical context, when and under what circumstances grazing occurred, is also an important consideration. Many of the dense ponderosa pine forests and less‐than‐desirable forest health conditions of today originated in the early 1900s. Contributing to that condition was a convergence of fire, climate, and grazing factors that were unique to that time. During that time period, substantially fewer low‐intensity ground fires (those that thinned dense stands of younger trees) were the result of reduced fine fuels (grazing), a substantial reduction in fires initiated by Native Americans, and effective fire‐suppression programs. Especially favorable climate years for tree reproduction occurred during the early 1900s. Exceptionally heavy, unregulated, unmanaged grazing by very large numbers of horses, cattle, and sheep during the late nineteenth and early twentieth centuries occurred in most of the U.S. West and beginning earlier in portions of the Southwest. Today, livestock numbers on public lands are substantially lower than they were during this time and grazing is generally managed. Grazing then and grazing now are not the same.
Inconclusiveness of Chytridiomycosis as the Agent in Widespread Frog Declines
Authors: McCALLUM HAMISH
Published: September 2005

Abstract: Although there is considerable evidence to support the hypothesis that the chytrid fungusBatrachochytrium dendrobatidisis the primary agent responsible for widespread declines in amphibian populations, particularly rainforest frog populations in Australia and Central America, I argue the case has not yet been made conclusively. Few specimens were collected at the time of population declines, so it may never be possible to conclusively determine their cause. It remains unclear whether the pathogen is novel where declines have occurred. Although it is not necessary that the infection be novel for it to be implicated in declines, if a preexisting pathogen has only recently caused extinctions, cofactors must be important. Whether the pattern of outbreaks represents a “wave” of extinctions is unclear, but if it does, the rate of spread in Australia is implausibly high for a waterborne pathogen, given the most likely estimates of epidemiological parameters. AlthoughB. dendrobatidisis an amphibian pathogen according to Koch's postulates, the postulates are neither necessary nor sufficient criteria to identify a pathogen. The following key pieces of information are necessary to better understand the impact of this fungus on frog communities: better knowledge of the means and rate of transmission under field conditions, prevalence of infection among frog populations, as distinct from morbid individuals, and the effect of the fungus on frogs in the wild. It is crucial to determine whether there are strains of the fungus with differing pathogenicity to particular frog species and whether host‐pathogen coevolution has occurred or is occurring. Recently developed diagnostic tools bring into reach the possibility of addressing these questions and thus developing appropriate strategies to manage frog communities that may be affected by this fungus.
Feral Goat Eradications on Islands
Authors: CAMPBELL KARL , DONLAN C. JOSH
Published: September 2005

Abstract:  Introduced mammals are major drivers of extinction. Feral goats (Capra hircus) are particularly devastating to island ecosystems, causing direct and indirect impacts through overgrazing, which often results in ecosystem degradation and biodiversity loss. Removing goat populations from islands is a powerful conservation tool to prevent extinctions and restore ecosystems. Goats have been eradicated successfully from 120 islands worldwide. With newly developed technology and techniques, island size is perhaps no longer a limiting factor in the successful removal of introduced goat populations. Furthermore, the use of global positioning systems, geographic information systems, aerial hunting by helicopter, specialized hunting dogs, and Judas goats has dramatically increased efficiency and significantly reduced the duration of eradication campaigns. Intensive monitoring programs are also critical for successful eradications. Because of the presence of humans with domestic goat populations on large islands, future island conservation actions will require eradication programs that involve local island inhabitants in a collaborative approach with biologists, sociologists, and educators. Given the clear biodiversity benefits, introduced goat populations should be routinely removed from islands.
Placenta growth factor stimulates the growth of Philadelphia chromosome positive acute lymphoblastic leukemia cells by both autocrine and paracrine pathways
Authors: Ikai Toshiko , Miwa Hiroshi , Shikami Masato , Hiramatsu Akihito , Tajima Emi , Yamamoto Hidesuke , Imai Norikazu , Hattori Akiko , Nishii Kazuhiro , Miura Kazuhisa , Satoh Atsushi , Itoh Masato , Imamura Akira , Mihara Hidetsugu , Katoh Yoshiro , Nitta Masakazu
Published: September 2005

Abstract:  Vascular endothelial growth factor (VEGF) and its associated molecule, placenta growth factor (PlGF) are now known to support normal hematopoiesis, and leukemia cell growth. In this study, expression of VEGF and PlGF in acute lymphoblastic leukemia (ALL) cells was examined by real time reverse transcription‐polymerase chain reaction in 20 patient samples. Expression of PlGF was more intense in Philadelphia chromosome positive (Ph+) ALL than in Ph− ALL cases. On the other hand, expression level of VEGF was not different between Ph+ and Ph− cases. Then, PlGF was added to the two ALL cell lines, CRL1929 (Ph+), and Nalm6 (Ph−). The PlGF stimulated the growth of CRL1929 in time‐ and dose‐dependent manners, although the growth of Nalm6 was not affected by PlGF. The growth stimulation of CRL1929 by PlGF was confirmed by the increase of S phase cells. And the growth promoting effect of PlGF on CRL1929 was cancelled by simultaneous addition of VEGFR1/Fc (which binds to PlGF and abrogates its function), but was not cancelled by VEGFR2/Fc (which does not bind to PlGF). Then, addition of VEGFR1/Fc to the simple culture of CRL1929 demonstrated growth inhibitory effect. These observations demonstrated that PlGF stimulates the growth of Ph+ ALL cells by both autocrine and paracrine pathways. Finally, PlGF‐VEGFR1 loop might be a therapeutic target to improve the prognosis of Ph+ ALL.
On mouse and man: neutrophil gelatinase associated lipocalin is not involved in apoptosis or acute response
Authors: Klausen Pia , Niemann Carsten U. , Cowland Jack B. , Krabbe Karen , Borregaard Niels
Published: September 2005

Abstract:  Neutrophil gelatinase‐associated lipocalin (NGAL) is a siderphore binding molecule present in the specific granules of neutrophils and induced in a variety of epithelial cells during inflammation. Its mouse orthologue, 24p3, is also an acute phase protein synthesized in the liver and adipose tissue during inflammation. 24p3 has recently been implicated in apoptosis of myeloid cells. We investigated whether similar features are characteristics of NGAL. First, isolated normal myeloid bone marrow cells were incubated with NGAL for 6 and 24 hr and analyzed for apoptosis by annexin V binding and by propidium iodide labeling. We found no indication that NGAL induces significant apoptosis in myeloid cells. Second, a human sepsis model where normal volunteers were given endotoxin 2 ng/kg intravenously, showed no evidence that NGAL is an acute phase protein. The plasma level of NGAL reflected the number of circulating neutrophils and was completely different from the kinetics of C‐reactive protein. We thus conclude that major differences exist between mouse and man with regards to the role of this lipocalin in myelopoiesis and inflammation.
Soluble transferrin receptor and zinc protoporphyrin – competitors or efficient partners?
Authors: Metzgeroth Georgia , Adelberger Verena , Dorn‐Beineke Alexandra , Kuhn Christian , Schatz Michael , Maywald Ole , Bertsch Thomas , Wisser Hermann , Hehlmann Rüdiger , Hastka Jan
Published: September 2005

Abstract:  Objectives: Soluble transferrin receptor (sTfR) and zinc protoporphyrin (ZPP) are both parameters of iron deficient erythropoiesis (IDE), the sTfR measurement is commonly regarded to be the more sensitive test. sTfR also reflects erythropoietic activity, it is increased in enhanced erythropoiesis. Methods: We investigated the diagnostic accuracy of sTfR in assessment of iron deficiency (ID) and compared it with ZPP. The study was performed on 174 subjects, in which ID has been precisely staged. Results: Individuals without ID and patients with storage iron depletion only, had normal sTfR values. Patients classified as IDE and patients with iron deficiency anemia had significantly increased sTfR. There was a good correlation between sTfR and hemoglobin (r = −0.86; P < 0.0001) and between sTfR and ZPP (r = 0.86; P < 0.0001). When diagnosing ID, ZPP was the more sensitive test. In mildly developed IDE associated with ZPP‐ratios between 40 and 70 μmol/mol heme, the sTfR concentration was elevated in only 25% of the cases. Reliably elevated sTfR values were observed only in more advanced IDE, associated with ZPP > 70 μmol/mol heme. Conclusions: ZPP is not inferior to sTfR when diagnosing IDE. Given the good correlation between sTfR and ZPP and because ZPP is uninfluenced by the erythropoietic activity, sTfR and ZPP are not competitors, rather efficient partners in diagnosing anemias. By measuring ZPP and sTfR simultaneously, the diagnostic uncertainty inherent in each of them individually can be eliminated. In particular, the simultaneous determination of ZPP and sTfR enhances the diagnostic power of sTfR in assessment of the erythropoietic activity.