bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Associated With Age of Diagnosis Among Children With Autism Spectrum Disorders
Authors: Mandell David S. , Novak Maytali M. , Zubritsky Cynthia D.
Published: December 2005

Objective. Early diagnosis of children with autism spectrum disorders (ASD) is critical but often delayed until school age. Few studies have identified factors that may delay diagnosis. This study attempted to identify these factors among a community sample of children with ASD.

Methods. Survey data were collected in Pennsylvania from 969 caregivers of children who had ASD and were younger than 21 years regarding their service experiences. Linear regression was used to identify clinical and demographic characteristics associated with age of diagnosis.

Results. The average age of diagnosis was 3.1 years for children with autistic disorder, 3.9 years for pervasive developmental disorder not otherwise specified, and 7.2 years for Asperger's disorder. The average age of diagnosis increased 0.2 years for each year of age. Rural children received a diagnosis 0.4 years later than urban children. Near-poor children received a diagnosis 0.9 years later than those with incomes >100% above the poverty level. Children with severe language deficits received a diagnosis an average of 1.2 years earlier than other children. Hand flapping, toe walking, and sustained odd play were associated with a decrease in the age of diagnosis, whereas oversensitivity to pain and hearing impairment were associated with an increase. Children who had 4 or more primary care physicians before diagnosis received a diagnosis 0.5 years later than other children, whereas those whose pediatricians referred them to a specialist received a diagnosis 0.3 years sooner.

Conclusion. These findings suggest improvements over time in decreasing the age at which children with ASD, especially higher functioning children, receive a diagnosis. They also suggest a lack of resources in rural areas and for near-poor families and the importance of continuous pediatric care and specialty referrals. That only certain ASD-related behaviors, some of which are not required to satisfy diagnostic criteria, decreased the age of diagnosis suggests the importance of continued physician education.
Regional Variation in Survival of People With Cerebral Palsy in the United Kingdom
Authors: Hemming Karla , Hutton Jane L. , Colver Allan , Platt Mary-Jane
Published: December 2005

Objectives. Regional variation in survival of people who have cerebral palsy (CP) has been observed but not previously investigated in detail. In addition to true differences, variations in the methods and definitions used, completeness of ascertainment, and the role of potential confounding factors all have been proposed as possible explanations for these observed variations. Our aim was to assess the regional differences in survival of young people with CP and the effect on survival of socioeconomic differences after adjustment for variations in level of impairment and birth characteristics.

Methods. Survival patterns for young people with CP were calculated using information from a collaborative database. This database consisted of registrations of children who were born with CP in 5 geographically defined areas in the United Kingdom between 1980 and 1996. Notification of subsequent deaths was provided by the relevant births and death register. We consider the effects of birth characteristics, socioeconomic status, and severity of CP on survival.

Results. There were 325 deaths among the 4007 cases of CP identified. The proportion of affected children who survived to 20 years of age ranged from 85% (Mersey-side and Cheshire, male individuals) to 94% (North of England, male individuals). Multivariate modeling showed that the severity of impairment had the biggest impact on survival and that additional contributions were made by birth weight and socioeconomic status but that after such adjustments regional differences were no longer significant.

Conclusions. The number and the severity of impairments are the best predictors of survival in young people with CP. After adjustment for the number of impairments, children who were born in affluent areas and had a low birth weight have an increased risk for death over those who were born with a normal birth weight. The same does not hold, however, for those who were born in deprived areas.
The Contribution of Withholding or Withdrawing Care to Newborn Mortality
Authors: Barton Lorayne , Hodgman Joan E.
Published: December 2005

Objective. We sought to determine the contribution of withholding or withdrawing care to neonatal mortality in our hospital over a 10-year period from 1993 through 2002.

Background. Although not initiating or withholding intensive care for certain newborns has been practiced openly for the past 25 years, little information has been published concerning the results of these practices on neonatal mortality.

Design and Methods. All infants who were born in our hospital and remained in the hospital until their death were evaluated for the care they received at the time of birth and near the time of their death. The contribution of not initiating care or withdrawing care to the neonatal mortality rates in our hospital was determined. Information was obtained directly from the patients' charts as well as the neonatal database and monthly neonatal mortality and morbidity review. Other information, if needed, was obtained from the monthly ethics committee reviews of all nursery deaths. Information was collected relating to birth weight, gestational age, diagnosis, time of death, and year of death. Hospital and neonatal unit protocols were evaluated to determine how closely they were followed.

Results. During the 10-year period, 380 deaths (0.8%) of a total of 47820 live births occurred in our hospital. Care was not initiated or was withdrawn in close to 72% of those deaths; total care until death occurred in 28%. Total care for infants who died over the 10-year period decreased markedly as care not initiated or care withdrawn increased. Most of this increase in not initiating care and in withdrawal of care was in the smaller of the extremely low birth weight infants.

Conclusions. The majority of nursery deaths of infants born in our hospital occurred as the result of selected noninitiating of care or as a result of withdrawing care in infants not responding or considered to have a futile outcome. Only slightly more than one quarter of the infants received total care until the time of death
Randomized, Controlled Trial of a Prenatal and Postnatal Lactation Consultant Intervention on Duration and Intensity of Breastfeeding up to 12 Months
Authors: Bonuck Karen A. , Trombley Michelle , Freeman Katherine , McKee Diane
Published: December 2005

Objective. To determine whether an individualized, prenatal and postnatal, lactation consultant intervention resulted in increased cumulative intensity of breastfeeding up to 52 weeks.

Design. The randomized, nonblinded, controlled trial recruited women from prenatal care. Baseline prenatal interviews covered demographic data and breastfeeding experience, intention, and knowledge. Interviews at 1, 2, 3, 4, 6, 8, 10, and 12 months after birth collected data on weekly feeding patterns, infant illness, and infant health care use.

Setting. Two community health centers serving low-income, primarily Hispanic and/or black women.

Participants. The analytic sample included 304 women (intervention: n = 145; control: n = 159) with ≥1 postnatal interview.

Intervention. Study lactation consultants attempted 2 prenatal meetings, a postpartum hospital visit, and/or home visits and telephone calls. Control subjects received the standard of care.

Outcome Measures. Cumulative breastfeeding intensity at 13 and 52 weeks, based on self-reports of weekly feeding, on a 7-level scale.

Results. The intervention group was more likely to breastfeed through week 20 (53.0% vs 39.3%). Exclusive breastfeeding rates were low and did not differ according to group. In multivariate analyses, control subjects had lower breastfeeding intensity at 13 weeks (odds ratio [OR]: 1.90; 95% confidence interval [CI]: 1.13–3.20) and 52 weeks (OR: 2.50; 95% CI: 1.48–4.21). US-born control subjects had lowest breastfeeding intensity at 13 weeks (OR: 5.22; 95% CI: 2.43–11.22) and 52 weeks (OR: 5.25; 95% CI: 2.44–11.29). There were no significant differences in breastfeeding intensity among the US-born intervention, foreign-born intervention, and foreign-born control groups.

Conclusions. This “best-practices” intervention was effective in increasing breastfeeding duration and intensity. Breastfeeding promotion should focus on US-born women and exclusive breastfeeding.
The Histrelin Implant: A Novel Treatment for Central Precocious Puberty
Authors: Hirsch Harry J. , Gillis David , Strich David , Chertin Boris , Farkas Amicur , Lindenberg Tzina , Gelber Hadassa , Spitz Irving M.
Published: December 2005

Objective. Standard treatment of central precocious puberty (CPP) consists of intramuscular or subcutaneous administration of a gonadotropin-releasing hormone (GnRH) agonist (GnRHa) at 3- to 4-week intervals. Although generally effective in suppressing clinical and laboratory parameters of puberty, GnRHa injections are painful, and the need for monthly clinic visits may contribute to poor compliance. Recently, a subcutaneous implant was developed that releases the GnRHa histrelin at an average rate of 65 μg/day. The aims of this study were to determine if a histrelin implant would suppress gonadotropin and estradiol (E2) in girls with CPP for 1 year and to compare the suppression to standard treatment.

Methods. We studied 11 girls with CPP to determine if the histrelin implant can maintain long-term gonadotropin suppression. Mean age at diagnosis was 6 years (range: 2–9 years). GnRH (100 μg intravenously) stimulation tests (GnRH-STs) showed peak luteinizing hormone and follicle-stimulating hormone responses of 23 ± 28 (mean ± SD) and 20 ± 25 mIU/mL, respectively. All subjects were initially treated with depot intramuscular GnRHa triptorelin embonate. Implants were inserted subcutaneously under local anesthesia, and depot GnRHa treatment was discontinued. Six girls were followed for 15 months after insertion (group A). For the remaining 5 girls, the implant was removed after 9 months, and a new implant was inserted at the same incision site (group B). GnRH-STs were performed before depot GnRHa treatment, immediately before implant insertion, at the 6- and 9-month visits for each patient and the 12- and 15-month visit for those girls followed for 15 months.

Results. In all girls, breast development regressed, growth velocity decreased, and bone-age advancement was slowed. Basal gonadotropins and their responses to GnRH-STs and E2 levels were suppressed. Peak luteinizing hormone and follicle-stimulating hormone responses to GnRH-STs at preinsertion versus 9 months were 1.30 ± 1.34 vs 0.25 ± 0.08 and 1.68 ± 1.08 vs 1.13 ± 0.55 mIU/mL, respectively. Basal and stimulated gonadotropin levels and E2 level remained suppressed in all 6 patients followed for 15 months after implant insertion. Patients and parents reported less pain and discomfort and less interference with school activity and work with the implant compared with standard monthly injections.

Conclusions. The histrelin implant consistently suppresses clinical and laboratory parameters of puberty for 1 year and is a promising new technique for treating CPP without the pain and inconvenience of monthly injections.
A Pilot Study of the Effectiveness of a School-Based Influenza Vaccination Program
Authors: King James C. , Cummings Ginny E. , Stoddard Jeffrey , Readmond Bernard X. , Magder Laurence S. , Stong Mary , Hoffmaster Margaret , Rubin Judith , Tsai Theodore , Ruff Elizabeth ,   for the SchoolMist Study Group
Published: December 2005

Objective. The objective of this study was to evaluate the feasibility of a school-based influenza immunization program.

Methods. Pupils and their families from 3 demographically similar elementary schools participated in this pilot, unblinded, controlled intervention study. Live attenuated influenza vaccine (FluMist) was made available to all eligible pupils in 1 target school during regular school hours. Two schools where vaccine was not offered served as control schools. All families from the 3 study schools were sent an anonymous questionnaire requesting 7-day recall data on fever or respiratory illness (FRI)-related medical visits, medications purchased, and days of school or paid work lost during the peak influenza week. Changes in weekly pupil absenteeism were also examined.

Results. One hundred eighty-five (40%) of the target school pupils received vaccine, of whom >50% were vaccinated ≤3 weeks before the influenza outbreak period. Questionnaires were returned by 43% to 51% of households. Significant (45–70%) relative reductions in FRI-related outcomes, including doctor visits by adults or children, prescription or other medicines purchased, and family schooldays or workdays missed, were observed for target school households, compared with control school households. The increases in absenteeism rates during the influenza outbreak period, compared with baseline rates earlier in the fall, were not significantly different between target and control schools. Within the target school, however, the increase in absenteeism rates was significantly smaller for the FluMist-vaccinated pupils, compared with the non–FluMist-vaccinated pupils.

Conclusions. This school-based influenza immunization program was associated with significant reductions in FRI-related outcomes in households of pupils attending an intervention school. These results might have underestimated the potential impact of FluMist, because the majority of children received intraepidemic vaccination.
An Epidemiologic Study of Orofacial Clefts with Other Birth Defects in Victoria, Australia
Authors: Vallino-Napoli Linda D. , Riley Merilyn M. , Halliday Jane L.
Published: December 2005

Objective:

To describe the epidemiological characteristics of oral clefts occurring with other birth defects in Victoria, Australia.

Methods:

Information on infants and fetuses reported to the Victorian Birth Defects Register from 1983 to 2000 was collected. Birth defects were classified as Pierre Robin Sequence, chromosomal anomaly, nonchromosomal syndrome, single-system defect, or multiple-system defect. Pregnancy outcome and associations with selected infant and maternal features was examined.

Results:

One third of the 2022 oral clefts recorded had other birth defects. There were more overall cleft cases involving multiple systems and chromosomal anomalies than any other birth defect group. The prevalence ratio of cleft lip with or without cleft palate (CL/P) was highest among multiple-system defects and chromosomal anomalies. Perinatal mortality was high, with termination of pregnancy highest in CL/P and chromosomal anomalies and multiple-system defects. There was a nonsignificant excess of clefts among multiple births. Women ≥40 years old had a tendency toward having a child with a cleft palate and another birth defect. There was an increased likelihood that women born in the U.K. would have a baby with CL/P and another birth defect.

Conclusions:

This is among the first reports in Victoria, Australia, describing oral clefts and other birth defects and associations between infant and maternal factors. Although some findings confirmed other population-based studies, some continued to be at variance. Nonetheless, the data derived support examination of babies diagnosed with clefts for associated comorbidities.
Mechanisms of endocrine resistance and novel therapeutic strategies in breast cancer
Authors: Normanno Nicola , Di Maio Massimo , De Maio Ermelinda , De Luca Antonella , de Matteis Andrea , Giordano Antonio , Perrone Francesco , _ _
Published: December 2005

Tamoxifen has been the mainstay of hormonal therapy in both early and advanced breast cancer patients for approximately three decades. The availability of novel compounds such as aromatase inhibitors (AIs) and fulvestrant, with different mechanism of action, is changing the scenario of endocrine treatment of postmenopausal breast cancer patients. In this review article, we have summarized the current knowledge of the mechanisms of resistance to endocrine therapy, in order to derive information that might be useful for therapeutic intervention. We propose that resistance to endocrine therapy is a progressive, step-wise phenomenon induced by the selective pressure of hormonal agents, which leads breast cancer cells from an estrogen-dependent, responsive to endocrine manipulation phenotype to a non-responsive phenotype, and eventually to an estrogen-independent phenotype. In particular, evidence suggests for each ‘action’ introduced to block estrogen stimulation of breast cancer cells (i.e. treatment with anti-estrogen), there are one or more corresponding ‘reactions’ that tumor cells can use to escape our attempts to block their growth: estrogen hypersensitivity associated with increased transcriptional activity of estrogen receptor α (ERα) and/or increased non-genomic activity of ERα, estrogen supersensitivity, increased growth factor signaling, suppression of ERα expression and finally estrogen independence. Activation of growth factor signaling is involved in each step of this phenomenon, and might ultimately substitute estrogen in sustaining the growth and the survival of breast cancer cells. In this respect, results of pre-clinical and clinical studies with AIs, fulvestrant and signaling inhibitors sustain this hypothesis. More importantly, the knowledge of the mechanisms involved in the resistance of breast cancer cells to endocrine therapy offers potential for novel therapeutic strategies.
Activity and function of the nuclear factor kappaB pathway in human parathyroid tumors
Authors: Corbetta S , Vicentini L , Ferrero S , Lania A , Mantovani G , Cordella D , Beck-Peccoz P , Spada A
Published: December 2005

Previous studies indicate that nuclear factor kappaB (NF-κB) transcription factor is deregulated and overexpressed in several human neoplasias. The aim of this study was to test the hypothesis that the NF-κB pathway may be involved in parathyroid tumorigenesis. For this purpose, we determined the level of NF-κB activity, evaluated as phosphorylation of the transcription subunit p65, its modulation by specific and non-specific agents and its impact on cyclin D1 expression. Phosphorylated p65 levels present in parathyroid neoplasias (n = 13) were significantly lower than those found in normal tissues (n = 3; mean optical density (OD) 0.19 ± 0.1 vs 0.4 ± 0.1, P = 0.007), but there was no significant difference between adenomas and secondary and multiple endocrine neoplasia type 1 (MEN1)-related hyperplasia. Conversely, MEN2A (Cys634Arg)-related parathyroid samples showed extremely high levels of phosphorylated p65 that exhibited a nuclear localization at immunohistochemistry (n = 3). Phosphorylated p65 levels negatively correlated with menin expression (r2 = 0.42, P = 0.05). Tumor necrosis factor-α (TNFα) caused a significant increase in phosphorylated p65 levels (183 ± 13.8% of basal) while calcium sensing receptor (CaR) agonists exerted a significant inhibition (19.2 ± 3.3% of basal). Although TNFα was poorly effective in increasing cyclin D1 expression, NF-κB blockade by the specific inhibitor BAY11-7082 reduced FCS-stimulated cyclin D1 by about 60%. Finally, the inhibitory effects of CaR and BAY11-7082 on cyclin D1 expression were not additive – by blocking NF-κB CaR activation did not induce a further reduction in cyclin D1 levels. In conclusion, the study demonstrated that in parathyroid tumors: (1) p65 phosphorylation was dramatically increased by RET constitutive activation and was negatively correlated with menin expression, (2) p65 phosphorylation was increased and reduced by TNFα and CaR agonists respectively, and (3) blockade of the NF-κB pathway caused a significant decrease in cyclin D1 expression.
Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition
Authors: Kaaks R , Rinaldi S , Key T J , Berrino F , Peeters P H M , Biessy C , Dossus L , Lukanova A , Bingham S , Khaw K-T , Allen N E , Bueno-de-Mesquita H B , van Gils C H , Grobbee D , Boeing H , Lahmann P H , Nagel G , Chang-Claude J , Clavel-Chapelon F , Fournier A , Thiébaut A , González C A , Quirós J R , Tormo M-J , Ardanaz E , Amiano P , Krogh V , Palli D , Panico S , Tumino R , Vineis P , Trichopoulou A , Kalapothaki V , Trichopoulos D , Ferrari P , Norat T , Saracci R , Riboli E
Published: December 2005

Considerable experimental and epidemiological evidence suggests that elevated endogenous sex steroids — notably androgens and oestrogens — promote breast tumour development. In spite of this evidence, postmenopausal androgen replacement therapy with dehydroepiandrosterone (DHEA) or testosterone has been advocated for the prevention of osteoporosis and improved sexual well-being. We have conducted a case–control study nested within the European Prospective Investigation into Cancer and Nutrition. Levels of DHEA sulphate (DHEAS), (Δ4-androstenedione), testosterone, oestrone, oestradiol and sex-hormone binding globulin (SHBG) were measured in prediagnostic serum samples of 677 postmenopausal women who subsequently developed breast cancer and 1309 matched control subjects. Levels of free testosterone and free oestradiol were calculated from absolute concentrations of testosterone, oestradiol and SHBG. Logistic regression models were used to estimate relative risks of breast cancer by quintiles of hormone concentrations. For all sex steroids –the androgens as well as the oestrogens – elevated serum levels were positively associated with breast cancer risk, while SHBG levels were inversely related to risk. For the androgens, relative risk estimates (95% confidence intervals) between the top and bottom quintiles of the exposure distribution were: DHEAS 1.69 (1.23–2.33), androstenedione 1.94 (1.40–2.69), testosterone 1.85 (1.33–2.57) and free testosterone 2.50 (1.76–3.55). For the oestrogens, relative risk estimates were: oestrone 2.07 (1.42–3.02), oestradiol 2.28 (1.61–3.23) and free oestradiol (odds ratios 2.13 (1.52–2.98)). Adjustments for body mass index or other potential confounding factors did not substantially alter any of these relative risk estimates. Our results have shown that, among postmenopausal women, not only elevated serum oestrogens but also serum androgens are associated with increased breast cancer risk. Since DHEAS and androstenedione are largely of adrenal origin in postmenopausal women, our results indicated that elevated adrenal androgen synthesis is a risk factor for breast cancer. The results from this study caution against the use of DHEA(S), or other androgens, for postmenopausal androgen replacement therapy.
Disappearance of a virilizing adrenal tumor following therapy with cyproterone acetate
Authors: Lasco A , Morini E , Maglitto D , Campennì A , Benvenga S
Published: December 2005

A 57-year-old woman presented with an apparently obvious diagnosis of iatrogenic virilization. At the age of 51, she began a 4-year treatment with prednisone or cyclosporine, which are known to promote hair growth, for Behçet disease. At the age of 56, osteoporosis was overtreated with the anabolic steroid nandrolone. Insignificant inhibition by dexamethasone of the extremely high serum concentrations of testosterone and less high concentrations of weak androgens prompted us to search for a virilizing tumor. Computed tomography showed a 2.3 × 1.5 cm nodule in the right adrenal gland. As the patient refused surgery, virilization was treated with the antiandrogen cyproterone acetate (CPA), but for only 4 months because clinical and hormone abnormalities reversed and the tumor was no longer visible. The patient remains symptom-free. This first report of a curative effect of CPA on a purely virilizing adrenal tumor opens new avenues in the management of such tumors.
Differential expression of IGF-binding protein-3 in normal and malignant colon and its influence on apoptosis
Authors: Jenkins P J , Khalaf S , Ogunkolade W , McCarthy K , David T , Hands R E , Davies D , Bustin S A
Published: December 2005

IGF-binding protein-3 (IGFBP-3) has been reported to exert a protective influence on the pathogenesis of colorectal cancer. This may reflect its modulation of IGF-I bioactivity as well as IGF-I-independent effects on cell proliferation and apoptosis. Although local expression of IGF-I in the colon is increasingly recognised as having important regulatory consequences, the role of locally expressed IGFBP-3 remains unknown. The aims of the present study were: (i) to quantify and localise the expression of IGFBP-3 in human normal and malignant colon; (ii) to relate this expression to that of other components of the IGF-I axis; and (iii) to investigate the effects of IGFBP-3 on colonic epithelial cell proliferation and apoptosis. RNA was extracted from 46 paired samples of normal and malignant colonic tissue. IGFBP-3, IGF-I, IGF-I receptor and GH receptor mRNA levels were quantified using real-time RT-PCR. Laser-capture microdissection of the same samples was used to isolate mRNA from epithelium and stromal components and localise mRNA expression. Expression was confirmed at a protein level by immunohistochemistry. Human colorectal cancer HT-29 and CaCo-2 cells were cultured with IGFBP-3 (200 ng/ml), +/− IGF-I (20 ng/ml), +/− sodium butyrate (5 mM). Cell number was assessed by an MTS assay (a modification of the MTT assay), and apoptosis assessed by cell morphology and FACS analysis using both annexin and propidium iodide staining. UO146, a MAP kinase inhibitor, and wortmannin, an inhibitor of the phosphatidylinositol 3-kinase (PI-3K) pathway, were used to determine the contribution of these signalling pathways on the effects of IGFBP-3. IGFBP-3 mRNA was detected in all samples (mean copy number/μg total RNA in normal colon, 2.6 × 106 compared with 1.3 × 107 in the cancers; P<0.0001). Immunohistochemistry confirmed the expression and showed it to be equally distributed between epithelial and stromal components in normal tissue, but to be mainly restricted to the stromal component of malignant tissue. This differential expression was confirmed by RT-PCR of RNA from laser-capture microdissected samples. IGF-I mRNA was detected in 31 samples of normal colon; mean IGFBP-3 copy number was higher in the IGF-I-positive samples compared with IGF-I-negative samples. IGFBP-3 on its own induced apoptosis in HT-29 cells (P<0.001). Co-incubation of 200 ng/ml IGFBP-3 with butyrate (5 mM) resulted in the potentiation of its apoptosis (P<0.0001), which was not rescued by co-incubation with IGF-I (P<0.0001). The addition of UO126 caused a decrease in cell number and increased the effects of IGFBP-3. IGFBP-3 is differentially expressed between stromal and epithelial components of normal and malignant colon, which may reflect its pro-apoptotic, IGF-I-independent effect on colonic epithelial cells. These effects are mediated in part by the PI-3K pathway in contrast to the MAP kinase pathway used by IGF-I.
Treatment of advanced neuroendocrine tumours with radiolabelled somatostatin analogues
Authors: Kaltsas G A , Papadogias D , Makras P , Grossman A B
Published: December 2005

Neuroendocrine tumours (NETs) constitute a heterogeneous group of tumours that frequently express cell membrane-specific peptide receptors, such as somatostatin receptors (SSTRs), and of which gastroenteropancreatic (GEP), carcinoid and pancreatic islet cell tumours exhibit the highest expression of SSTRs. Radiolabelled receptor-binding somatostatin analogues (octreotide and lanreotide) act as vehicles to guide radioactivity to tissues expressing SSTRs, and can thus be used for their diagnosis and treatment. After the localization of NETs bearing SSTRs with 111In-octreotide (OctreoScan), a number of radioisotopes with different physical properties have been used for their treatment. The administration of high doses of the Auger electron and γ-emitter 111In-diethylenetriaminepenta-acetic acid (DTPA)0,octreotide in patients with metastatic tumours has been associated with considerable symptomatic improvement but relatively few and short-lived objective tumour responses. The use of another radiolabelled somatostatin analogue coupled with 90Y, a pure β-emitter, 90Y-1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA)0,Tyr3,octreotide (90Y-DOTATOC, OctreoTher), was associated with 10–30% objective tumour response rates, and appears to be particularly effective in larger tumours. 111In- and 90Y-DOTA-lanreotide has also been used for the treatment of NETs although its therapeutic efficacy is probably inferior to that of octreotide-based radiopharmaceuticals. More recently, treatment with 177Lu-DOTA0,Tyr3octreotate (177Lu-DOTATATE), which has a higher affinity for the SSTR subtype 2, resulted in approximately 30% complete or partial tumour responses; this radiopharmaceutical is particularly effective in smaller tumours. Furthermore, treatment using both 90Y-DOTATOC and 177Lu-DOTA0,Tyr3octreotate seems promising, as the combination of these radiopharmaceuticals could be effective in tumours bearing both small and large lesions. Tumour regression is positively correlated with a high level of uptake on 111In-octreotide scintigraphy, limited tumour mass and good performance status. In general, better responses have been obtained in GEP tumours than other NETs. The side effects of this form of therapy are relatively few and mild, particularly when kidney-protective agents are used. Treatment with radiolabelled somatostatin analogues presents a promising tool for the management of patients with inoperable or disseminated NETs, and particularly GEP tumours.
The study of oxide‐interface and grain‐boundary traps in poly‐Si TFT characteristics and its application to fabrication process diagnosis
Authors: Kimura M. , Yasuhara T. , Harada K. , Abe D. , Inoue S. , Shimoda T.
Published: December 2005

Abstract— The study of oxide‐interface and grain‐boundary traps in poly‐Si TFT characteristics is reviewed. The subthreshold swing and threshold voltage mainly depend on the density of the oxide‐interface traps (Dit), while the transistor mobility mainly depends on the density of grain‐boundary traps (Dgb). These device properties are applied to diagnose two fabrication processes: plasma treatment and gate‐oxide deposition. It is found that oxygen (O) plasma treatment reduces Dit. This seems to be because O plasma treatment has the ability to terminate the dangling bonds, but O plasma species do not diffuse into the poly‐Si. A model is proposed by comparing the bond energy of the Si‐H and Si‐O‐H. On the other hand, plasma‐enhanced chemical‐vapor deposition (PECVD) of tetraethylorthosilicate (TEOS) for gate oxide increases Dgb. This seems to be because hydrogen (H) plasma species in the TEOS‐PECVD damage the grain boundaries. A model is proposed by considering the reaction processes: hydrolysis, dehydration and bonding, and H plasma species generated during the dehydration.
Contraceptive Choices: Is the Future with Men?
Authors: Anderson R A , Walton M J
Published: December 2005

A credible, reversible male contraceptive with sufficient efficacy and convenience to rival established female methods has been eagerly awaited for some years. What are the issues surrounding its development and when is a launch likely? At present, many different approaches and targets have been identified for further development. These include spermatogenesis, unique testicular proteins, immunocontraception, the vas deferens and the potential method currently closest to fruition, hormonal contraception. This is now in Phase III studies in China and commercial studies are underway in Europe.
Potential Role of Androgens in the Treatment of Hypoactive Sexual Desire in Women
Authors: Clayton Anita H
Published: December 2005

Evaluation of: van Anders SM, Chernick AB, Chernick BA et al.: Preliminary clinical experience with androgen administration for pre- and postmenopausal women with hypoactive sexual desire. J. Sex Marital Ther. 31, 173–185 (2005).

There has been significant debate about the potential role of androgens in the treatment of hypoactive sexual desire in women. In this study, pre- and postmenopausal women with hypoactive sexual desire were age-matched with women without such complaints (n = 33). The treatment group received 100 mg of testosterone cypionate intramuscularly once a month for 3 months. Measures of salivary testosterone indicated no difference between groups at baseline, with an increase in testosterone levels in the hypoactive sexual desire group post-treatment. While significant differences existed between the two groups at baseline in scores on the Sexual Desire Inventory, the treated women demonstrated a significant increase in sexual desire post-treatment, with no difference in Sexual Desire Inventory scores at study end point. This study suggests that supplemental testosterone may improve sexual desire in women with hypoactive sexual desire without hypoandrogenism.
Breast Cancer Treatment During Pregnancy
Authors: Theriault Richard L , Rieber Alyssa G
Published: December 2005

The diagnosis of breast cancer during pregnancy, athough uncommon, can be a devastating and confusing diagnosis for many women. Many clinicians are unaware of the treatment options available for the pregnant patient and are unable to counsel their patients. The treatment of pregnancy-associated breast cancer is determined by the age of gestation and the stage of cancer at presentation. A multidisciplinary approach involving a medical oncologist, surgical oncologist, radiation oncologist and high-risk obstetrician will lead to an optimal outcome for the mother and child. This article will discuss the management of a pregnant patient with breast cancer.
Need for Weight Management among Postmenopausal Early Breast Cancer Patients Receiving Adjuvant Endocrine Therapy
Authors: Harvie Michelle , Howell Tony
Published: December 2005

Increasingly effective adjuvant therapies mean that the prognosis for postmenopausal women with breast cancer has never been better. Weight problems are common among breast cancer patients and worsen due to the impact of diagnosis and treatment. Recent studies have linked excess weight with the risk of recurrence of breast cancer among premenopausal women. While general obesity (body mass index) does not appear to influence the already much improved prognosis for postmenopausal women, there is some evidence that limiting central obesity and improving insulin resistance may improve survival. The focus of attention for postmenopausal breast cancer survivors is also shifting to consider the mortality and morbidity from other weight-related cancers and noncancer causes, such as cardiovascular disease, making weight control a potentially important adjunct to endocrine therapy. This paper outlines the rationale and optimal design for effective weight management strategies among postmenopausal breast cancer patients receiving endocrine therapy.
Von Willebrand Disease and other Disorders of Hemostasis in the Patient with Menorrhagia
Authors: Kouides Peter A
Published: December 2005

Separately, von Willebrand disease and menorrhagia are two relatively common conditions; in combination they occur at a prevalence of approximately 11–16%. Such patients exhibit a reduced quality of life and can incur a relatively high rate of gynecologic interventions; for example dilatation and curettage, endometrial ablation and hysterectomy. Initial evaluation involves a focused history for the following bleeding symptoms: menorrhagia since menarche, easy bruising of greater than 5 cm 1–2 times/month, frequent gum bleeding when flossing or brushing teeth or epistaxis 1–2 times/month. In addition, for those who have already undergone invasive interventions with the subsequent risk for hemorrhage, inquiry should be made regarding excessive bleeding with childbirth, dental tooth extraction and/or surgery. Step-wise testing includes a complete blood cell count and an assessment of the prothrombin time, activated partial thromboplastin time, iron profile, serum creatinine and thyroid-stimulating hormone level, followed by Factor VIII level, von Willebrand factor antigen and ristocetin cofactor, followed by consideration of platelet aggregation studies. Additional hemostatic studies may include obtaining a Factor XI level and euglobulin clot lysis time. Intuitively, failure to diagnose an underlying hemostatic disorder may lead to continued menorrhagia and diminished quality of life, as well as unnecessary surgical interventions that may in turn be fraught with an increased risk of bleeding. The management of von Willebrand disease-related menorrhagia involves consideration of the patient's age, childbearing status and preference. In the adolescent, surgical intervention is not an option, whereas an older patient beyond her childbearing years may choose a hysterectomy as a definitive treatment in lieu of continued medical therapy with intranasal/subcutaneous 1-deamino-8-D-arginine vasopressin (DDAVP), oral antifibrinolytic agents or oral contraceptive. The sexually active patient may initially choose a trial of oral contraceptive or the levonorgestrel intrauterine device, Mirena®. Pending ongoing comparative trials in von Willebrand disease-related menorrhagia of intranasal DDAVP, tranexamic acid and the levonorgestrel intrauterine device, specific recommendations cannot be made at present regarding the superiority of one intervention compared with another. It should also be noted that the dose and schedule of intranasal DDAVP, tranexamic acid and ε-amino caproic acid have not been well established and warrant further study in combination and at various doses and schedules.
Intersections between Adverse Pregnancy Outcomes
Authors: Ness Roberta B
Published: December 2005

Reproductive failure in a variety of forms, whether it be infertility, miscarriage, pre-eclampsia, prematurity or intrauterine growth restriction, may aggregate within individuals. This observation, although rarely studied, suggests that single pathophysiologies may be associated with a variety of reproductive morbidities. In this review, hyperimmune responsiveness to pregnancy is provided as one example of a process leading to a multitude of adverse impacts on healthy childbearing. Further research on reproductive failure as a spectrum is warranted.
Current Treatment Options for Vulvovaginal Candidiasis
Authors: Sobel Jack
Published: December 2005

For practitioners, selecting successful therapy for vulvovaginal candidiasis is anything but trivial. The dominant problem; however, lies not with selecting the correct antimycotic agent, but with making the correct diagnosis and not treating non-yeast infections and noninfections as yeast-induced. Moreover, not all cases of vulvovaginal candidiasis are equal and practitioners owe patients the obligation of selecting appropriate therapy based upon the specific type and severity of vulvovaginal candidiasis. Uncomplicated candidiasis is readily treated with short-term oral or topical therapy, whereas complicated candidiasis needs additional strategies using the plethora of therapies available. Problematic refractory cases still abound and the pipeline for new, more potent antifungal agents is largely empty. Management strategies for complicated Candida vaginitis are discussed.
Pharmacologic Treatment Options for Hypoactive Sexual Desire Disorder
Authors: Bolour Sheila Y , Braunstein Glenn D
Published: December 2005

Hypoactive sexual desire disorder is the most common cause of sexual dysfunction in women. According to a national survey, approximately a third of all women experience low sexual desire. The etiology of the disorder is often multifactorial. Research in treatment options for hypoactive sexual desire disorder is limited. In this article, treatment options including sex therapy, hormone therapy (estrogen, testosterone, dehydroepiandrosterone, tibolone), non-hormonal medical therapies (buproprion, buspirone, phosphodiesterase-5 inhibitors, amantadine and apomorphine) and herbal therapies (Avlimil®, Arginmax®, Zestra®, yohimbine and Ginkgo biloba) are reviewed.
Treating Urogenital Atrophy
Authors: Brown Candace , Bachman Gloria
Published: December 2005

Urogenital atrophy, although a frequently occurring symptom of aging for all women, is a condition often not thought of as a symptom of distress for older women or a sign of pelvic pathology requiring treatment by clinicians. Rather, many clinicians feel it is an expected consequence of aging, and older women themselves assimilate their lifestyle to the uncomfortable symptoms of dryness, irritation, itching and malodorous discharge. At times, when symptoms become intolerable with coitus, women will abandon sexual intercourse with their partners due to dyspareunia and not seek intervention to reverse the condition owing to embarrassment in raising this sensitive topic. When urogenital atrophy is diagnosed and the patient requests treatment, the gold standard intervention is estrogen, which can either be delivered systemically or vaginally. Since the Women's Health Initiative data, low-dose, vaginally delivered estrogen is recommended.
Gemcitabine in Combination with Paclitaxel for the Treatment of Metastatic Breast Cancer
Authors: Colomer Ramon
Published: December 2005

Gemcitabine and paclitaxel are active drugs in the treatment of patients with metastatic breast cancer which seem to have synergistic anticancer activity. Seven Phase II trials of gemcitabine/paclitaxel and one Phase III trial have been published. Two dosing or admistration schedules have been preferred in the clinical development of the combinations: gemcitabine on days 1 and 8 plus paclitaxel on day 1 or 8, every 3 weeks or gemcitabine plus paclitaxel on day 1, every 2 weeks. In first-line Phase II trials, up to 71% of patients responded to gemcitabine/paclitaxel therapy. Response rates were lower among patients who had received previous chemotherapy for metastatic disease (46%). Responses were observed in patients refractory to docetaxel monotherapy. Toxicity of gemcitabine/paclitaxel regimens has been low, with infrequent neutropenia or nonhematologic toxicity. In the randomized Phase III registration trial, the gemcitabine/paclitaxel combination demonstrated a clear advantage over paclitaxel alone in terms of the primary end point of survival and other efficacy end points, with manageable toxicity. Gemcitabine/paclitaxel showed a survival advantage of approximately 22% over paclitaxel alone (hazard ratio of 0.775). Gemcitabine plus paclitaxel represents an active and well-tolerated treatment alternative for first-line treatment of anthracycline-treated metastatic breast cancer. Triplet combinations, in which an anthracycline or trastuzumab are added to gemcitabine/paclitaxel, are being explored in the metastatic and neoadjuvant settings with excellent results. In addition, gemcitabine/paclitaxel is being evaluated in two large adjuvant multicenter studies.
Different Subtypes of Uterine Sarcoma Require a Separate Therapeutic Approach
Authors: Amant Frederic
Published: December 2005

Uterine sarcomas include a variety of mono- and biphasic malignancies, whereas tumor biology varies from an indolent and hormone-sensitive growth pattern to an aggressive and nonresponsive disease that is inevitably fatal. Insight into these different entities has only been gained after careful analysis of clinical, pathologic and molecular characteristics during the last few years. Furthermore, the rarity of uterine sarcomas has motivated many to collect data from different subtypes and to report on the collective data in order to report on larger numbers. The current overview aims to provide insights of clinical importance into each type of uterine sarcoma, with a special emphasis on treatment modalities.
Managing Mother-to-Child Transmission of HIV Infection in Developed-Country Settings
Authors: Thorne Claire , Newell Marie-Louise
Published: December 2005

This article reviews current understanding of the management of mother-to-child transmission of HIV-1 infection in the context of developed-country settings. The advent of highly active antiretroviral therapy has facilitated the virtual elimination of mother-to-child transmission of HIV infection in developed countries, reducing transmission rates to approximately 1–2%. This review describes the epidemiology of HIV infection among women of child-bearing age and the risk factors, timing and mechanisms of mother-to-child transmission, followed by a discussion of the identification of pregnant HIV-infected women and their therapeutic and obstetric management.
Gender Issues in Inflammatory Bowel Disease
Authors: Kane Sunanda
Published: December 2005

Crohn's disease and ulcerative colitis are two chronic inflammatory conditions involving the gastrointestinal tract. While many aspects of the management of these diseases are identical for all patients, there are some issues specific to women that are not necessarily part of routine care. Certain gender-specific issues such as menses, fertility, pregnancy and menopause are often overlooked and mismanaged. Women have different psychologic concerns compared with men in regard to their self-image and impact of disease. Healthcare providers, regardless of their primary focus, should be aware of these differences and be familiar with general information specific to women.
Treatment of Fibromyalgia: A Changing of the Guard
Authors: Holman Andrew J
Published: December 2005

Fibromyalgia remains one of the most common and enigmatic musculoskeletal disorders among patients with pain and, until recently, few effective treatments have been discovered. This review will briefly consider the rationale supporting traditional treatment options and their efficacy, including the role of exercise and pharmacotherapy. Juxtaposed with these common approaches to relieve fibromyalgia pain and fatigue are the promising new medications that are being developed, such as pregabalin, milnacipran, duloxetine, sodium oxybate, ropinirole and pramipexole. Outcomes from recent randomized trials will be reviewed and compared.
Chlamydia in Gynecologic Practice
Authors: Norman Jane
Published: December 2005

The focus on Chlamydia trachomatis in gynecologic practice 20 years ago was in treating its potential consequences: pelvic inflammatory disease, infertility and ectopic pregnancy. Although these conditions are still important, the current focus of C. trachomatis management for the obstetrician and gynecologist is early detection and treatment. The majority of women with C. trachomatis are asymptomatic, therefore, screening programs are being devised so that C. trachomatis can be treated prior to the occurence of any adverse consequences. Novel tests have allowed the use of urine samples and self-collected vulvovaginal swabs in the detection of C. trachomatis. This article will review the consequences of C. trachomatis infection in women, methods of identification of the organism, the prevalence in various populations, and treatment and screening strategies.
Olfactometry with Mice
Authors: Slotnick Burton , Restrepo Diego
Published: December 2005

A computer‐controlled, multiple‐channel odor generator, operant test chamber, and discrimination training procedure for mice are described. The odor generator allows controlled presentation of any one or combinations of eight odors to an odor‐sampling port that contains a liquid reinforcement delivery tube that also serves to detect responses. A modified discrete trial operant conditioning procedure provides measures of both response accuracy and response rate during anticipation of stimulus delivery and in the presence of two different odor stimuli. Results from numerous experiments demonstrate that, with these methods, mice reliably and rapidly acquire odor detection and a variety of odor‐discrimination tasks, and that response rate in the presence of the odor reflects the incentive motivation of stimuli that are or are not associated with reward.