bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the utilization of the preanaesthetic clinics in a University teaching hospital
Authors: Hariharan Seetharaman , Chen Deryk , Merritt-Charles Lorna
Published: May 2006

Background

Dedicated out-patient preanaesthetic clinics are relatively recent phenomenon and information is sparse from developing world. This study attempted to evaluate the utilization of adult and paediatric preanaesthetic clinics and its impact on the cancellations of surgery in Trinidad.

Methods

All patients scheduled to have elective surgery during the period of twelve weeks were enrolled for prospective collection of data including demographics, the admitting diagnoses, surgical procedure, category of surgery and specialty, and the patients' attendance to preanaesthetic clinics. Cancellations on the day of surgery along with reasons were recorded. The difference between patients who attended and did not attend the clinic was analysed.

Results

Of 424 patients scheduled for procedures during the study period, 213 were adults and 211 were children. Overall 39% of adults and 46% of the children scheduled for surgery had previously attended the preanaesthetic clinic. Among adults, general surgery patients were the largest majority to attend the preanaesthetic clinic. The paediatric preanaesthetic clinic was mostly utilized by paediatric general surgery. Overall 30% of procedures in adults and 26% of those in children were cancelled. There was a statistically significant difference in cancellations between patients who attended and did not attend the preanaesthetic clinic (p = 0.004). There was a 52% more chance of the procedure getting cancelled if the patient did not attend the clinic.

Conclusion

The study highlights the inadequate use of the preanaesthetic clinics and the impact of the clinics on last-minute cancellations.
Determinants of staff job satisfaction of caregivers in two nursing homes in Pennsylvania
Authors: Castle Nicholas G , Degenholtz Howard , Rosen Jules
Published: May 2006

Background

Job satisfaction is important for nursing home staff and nursing home management, as it is associated with absenteeism, turnover, and quality of care. However, we know little about factors associated with job satisfaction and dissatisfaction for nursing home workers.

Methods

In this investigation, we use data from 251 caregivers (i.e., Registered Nurses, Licensed Practical Nurses, and Nurse Aides) to examine: job satisfaction scores of these caregivers and what characteristics of these caregivers are associated with job satisfaction. The data were collected from two nursing homes over a two and a half year period with five waves of data collection at six-month intervals. The Job Description Index was used to collect job satisfaction data.

Results

We find that, overall nursing home caregivers are satisfied with the work and coworkers, but are less satisfied with promotional opportunities, superiors, and compensation. From exploratory factor analysis three domains represented the data, pay, management, and work. Nurse aides appear particularly sensitive to the work domain. Of significance, we also find that caregivers who perceived the quality of care to be high have higher job satisfaction on all three domains than those who do not.

Conclusion

These results may be important in guiding caregiver retention initiatives in nursing homes. The finding for quality may be especially important, and indicates that nursing homes that improve their quality may have a positive impact on job satisfaction of staff, and thereby reduce their turnover rates.
Care seeking behaviour for childhood illness- a questionnaire survey in western Nepal
Authors: Sreeramareddy Chandrashekhar T , Shankar Ravi P , Sreekumaran Binu V , Subba Sonu H , Joshi Hari S , Ramachandran Uma
Published: May 2006

Background

The World Health Organization estimates that seeking prompt and appropriate care could reduce child deaths due to acute respiratory infections by 20%. The purpose of our study was to assess care seeking behaviour of the mothers during childhood illness and to determine the predictors of mother's care seeking behaviour.

Methods

A cross-sectional survey was conducted in the immunization clinics of Pokhara city, Kaski district, western Nepal. A trained health worker interviewed the mothers of children suffering from illness during the preceding 15 days.

Results

A total of 292 mothers were interviewed. Pharmacies (46.2%) were the most common facilities where care was sought followed by allopathic medical practitioners (26.4%). No care was sought for 8 (2.7%) children and 26 (8.9%) children received traditional/home remedies. 'Appropriate', 'prompt' and 'appropriate and prompt' care was sought by 77 (26.4%), 166 (56.8%) and 33 (11.3%) mothers respectively. The mothers were aware of fever (51%), child becoming sicker (45.2%) and drinking poorly (42.5%) as the danger signs of childhood illness. By multiple logistic regression analysis total family income, number of symptoms, mothers' education and perceived severity of illness were the predictors of care seeking behaviour.

Conclusion

The results of the present study show that the mothers were more likely to seek care when they perceived the illness as 'serious'. Poor maternal knowledge of danger signs of childhood illness warrants the need for a complementary introduction of community-based Integrated Management of Childhood Illness programmes to improve family's care seeking behaviour and their ability to recognize danger signs of childhood illness. Socioeconomic development of the urban poor may overcome their financial constraints to seek 'appropriate' and 'prompt' care during the childhood illness.
Concomitant infections of Plasmodium falciparum and Wuchereria bancroftion the Kenyan coast
Authors: Muturi Ephantus J , Mbogo Charles M , Mwangangi Joseph M , Ng'ang'a Zipporah W , Kabiru Ephantus W , Mwandawiro Charles , Beier John C
Published: May 2006

Background

Anopheles gambiae s.l. and An. funestus are important vectors of malaria and bancroftian filariasis, which occur as co-endemic infections along the Kenyan Coast. However, little is known about the occurrence and prevalence of concomitant infections of the two diseases in mosquito and human populations in these areas. This study reports the prevalence of concomitant infections of Plasmodium falciparum and Wuchereria bancrofti in mosquito and human populations in Jilore and Shakahola villages in Malindi, Kenya.

Methods

Mosquitoes were sampled inside houses by pyrethrum spray sheet collection (PSC) while blood samples were collected by finger prick technique at the end of entomological survey.

Results

A total of 1,979 female Anopheles mosquitoes comprising of 1,919 Anopheles gambiae s.l and 60 An. funestus were collected. Concomitant infections of P. falciparum sporozoites and filarial worms occurred in 1.1% and 1.6% of An. gambiae s.l collected in Jilore and Shakahola villages respectively. Wuchereria-infected mosquitoes had higher sporozoite rates compared to non-infected mosquitoes, but multiple infections appeared to reduce mosquito survivorship making transmission of such infections rare. None of the persons examined in Shakahola (n = 107) had coinfections of the two parasites, whereas in Jilore (n = 94), out of the 4.3% of individuals harbouring both parasites, 1.2% had P. falciparum gametocytes and microfilariae and could potentially infect the mosquito with both parasites simultaneously.

Conclusion

Concerted efforts should be made to integrate the control of malaria and bancroftian filariasis in areas where they co-exist.
Aboriginal status is a prognostic factor for mortality among antiretroviral naïve HIV-positive individuals first initiating HAART
Authors: Lima Viviane D , Kretz Patricia , Palepu Anita , Bonner Simon , Kerr Thomas , Moore David , Daniel Mark , Montaner Julio SG , Hogg Robert S
Published: May 2006

Background

Although the impact of Aboriginal status on HIV incidence, HIV disease progression, and access to treatment has been investigated previously, little is known about the relationship between Aboriginal ethnicity and outcomes associated with highly active antiretroviral therapy (HAART). We undertook the present analysis to determine if Aboriginal and non-Aboriginal persons respond differently to HAART by measuring HIV plasma viral load response, CD4 cell response and time to all-cause mortality.

Methods

A population-based analysis of a cohort of antiretroviral therapy naïve HIV-positive Aboriginal men and women 18 years or older in British Columbia, Canada. Participants were antiretroviral therapy naïve, initiated triple combination therapy between August 1, 1996 and September 30, 1999. Participants had to complete a baseline questionnaire as well as have at least two follow-up CD4 and HIV plasma viral load measures. The primary endpoints were CD4 and HIV plasma viral load response and all cause mortality. Cox proportional hazards models were used to determine the association between Aboriginal status and CD4 cell response, HIV plasma viral load response and all-cause mortality while controlling for several confounder variables.

Results

A total of 622 participants met the study criteria. Aboriginal status was significantly associated with no AIDS diagnosis at baseline (p = 0.0296), having protease inhibitor in the first therapy (p = 0.0209), lower baseline HIV plasma viral load (p < 0.001), less experienced HIV physicians (P = 0.0133), history of IDU (p < 0.001), not completing high school (p = 0.0046), and an income of less than $10,000 per year (p = 0.0115). Cox proportional hazards models controlling for clinical characteristics found that Aboriginal status had an increased hazard of mortality (HR = 3.12, 95% CI: 1.77–5.48) but did not with HIV plasma viral load response (HR = 1.15, 95% CI: 0.89–1.48) or CD4 cell response (HR = 0.95, 95% CI: 0.73–1.23).

Conclusion

Our study demonstrates that HIV-infected Aboriginal persons accessing HAART had similar HIV treatment response as non-Aboriginal persons but have a shorter survival. This study highlights the need for continued research on medical interventions and behavioural changes among HIV-infected Aboriginal and other marginalized populations.
Effect of Ebola virus proteins GP, NP and VP35 on VP40 VLP morphology
Authors: Johnson Reed F , Bell Peter , Harty Ronald N
Published: May 2006

Recently we described a role for Ebola virus proteins, NP, GP, and VP35 in enhancement of VP40 VLP budding. To explore the possibility that VLP structure was altered by co-expression of EBOV proteins leading to the observed enhancement of VP40 VLP budding, we performed density gradient analysis as well as electron microscopy studies. Our data suggest that VP40 is the major determinant of VLP morphology, as co-expression of NP, GP and VP35 did not significantly change VLP density, length, and diameter. Ultra-structural changes were noted in the core of the VLPs when NP was co-expressed with VP40. Overall, these findings indicate that major changes in morphology of VP40 VLPs were likely not responsible for enhanced budding of VP40 VLPs in the presence of GP, NP and/or VP35.
Contribution of cysteine residues in the extracellular domain of the F protein of human respiratory syncytial virus to its function
Authors: Day Nicole D , Branigan Patrick J , Liu Changbao , Gutshall Lester L , Luo Jianquan , Melero José A , Sarisky Robert T , Del Vecchio Alfred M
Published: May 2006

The mature F protein of all known isolates of human respiratory syncytial virus (HRSV) contains fifteen absolutely conserved cysteine (C) residues that are highly conserved among the F proteins of other pneumoviruses as well as the paramyxoviruses. To explore the contribution of the cysteines in the extracellular domain to the fusion activity of HRSV F protein, each cysteine was changed to serine. Mutation of cysteines 37, 313, 322, 333, 343, 358, 367, 393, 416, and 439 abolished or greatly reduced cell surface expression suggesting these residues are critical for proper protein folding and transport to the cell surface. As expected, the fusion activity of these mutations was greatly reduced or abolished. Mutation of cysteine residues 212, 382, and 422 had little to no effect upon cell surface expression or fusion activity at 32°C, 37°C, or 39.5°C. Mutation of C37 and C69 in the F2 subunit either abolished or reduced cell surface expression by 75% respectively. None of the mutations displayed a temperature sensitive phenotype.
A single-particle characterization of a mobile Versatile Aerosol Concentration Enrichment System for exposure studies
Authors: Freney Evelyn J , Heal Mathew R , Donovan Robert J , Mills Nicholas L , Donaldson Kenneth , Newby David E , Fokkens Paul HB , Cassee Flemming R
Published: May 2006

Background

An Aerosol Time-of-Flight Mass Spectrometer (ATOFMS) was used to investigate the size and chemical composition of fine concentrated ambient particles (CAPs) in the size range 0.2–2.6 μm produced by a Versatile Aerosol Concentration Enrichment System (VACES) contained within the Mobile Ambient Particle Concentrator Exposure Laboratory (MAPCEL). The data were collected during a study of human exposure to CAPs, in Edinburgh (UK), in February-March 2004. The air flow prior to, and post, concentration in the VACES was sampled in turn into the ATOFMS, which provides simultaneous size and positive and negative mass spectral data on individual fine particles.

Results

The particle size distribution was unaltered by the concentrator over the size range 0.2–2.6 μm, with an average enrichment factor during this study of ~5 (after dilution of the final air stream). The mass spectra from single particles were objectively grouped into 20 clusters using the multivariate K-means algorithm and then further grouped manually, according to similarity in composition and time sequence, into 8 main clusters. The particle ensemble was dominated by pure and reacted sea salt and other coarse inorganic dusts (as a consequence of the prevailing maritime-source climatology during the study), with relatively minor contributions from carbonaceous and secondary material. Very minor variations in particle composition were noted pre- and post-particle concentration, but overall there was no evidence of any significant change in particle composition.

Conclusion

These results confirm, via single particle analysis, the preservation of the size distribution and chemical composition of fine ambient PM in the size range 0.2–2.6 μm after passage through the VACES concentration instrumentation.
Correction of patient positioning errors based on in-line cone beam CTs: clinical implementation and first experiences
Authors: Thilmann Christoph , Nill Simeon , Tücking Thomas , Höss Angelika , Hesse Bernd , Dietrich Lars , Bendl Rolf , Rhein Bernhard , Häring Peter , Thieke Christian , Oelfke Uwe , Debus Juergen , Huber Peter
Published: May 2006

Background

The purpose of the study was the clinical implementation of a kV cone beam CT (CBCT) for setup correction in radiotherapy.

Patients and methods

For evaluation of the setup correction workflow, six tumor patients (lung cancer, sacral chordoma, head-and-neck and paraspinal tumor, and two prostate cancer patients) were selected. All patients were treated with fractionated stereotactic radiotherapy, five of them with intensity modulated radiotherapy (IMRT). For patient fixation, a scotch cast body frame or a vacuum pillow, each in combination with a scotch cast head mask, were used. The imaging equipment, consisting of an x-ray tube and a flat panel imager (FPI), was attached to a Siemens linear accelerator according to the in-line approach, i.e. with the imaging beam mounted opposite to the treatment beam sharing the same isocenter. For dose delivery, the treatment beam has to traverse the FPI which is mounted in the accessory tray below the multi-leaf collimator. For each patient, a predefined number of imaging projections over a range of at least 200 degrees were acquired. The fast reconstruction of the 3D-CBCT dataset was done with an implementation of the Feldkamp-David-Kress (FDK) algorithm. For the registration of the treatment planning CT with the acquired CBCT, an automatic mutual information matcher and manual matching was used.

Results and discussion

Bony landmarks were easily detected and the table shifts for correction of setup deviations could be automatically calculated in all cases. The image quality was sufficient for a visual comparison of the desired target point with the isocenter visible on the CBCT. Soft tissue contrast was problematic for the prostate of an obese patient, but good in the lung tumor case. The detected maximum setup deviation was 3 mm for patients fixated with the body frame, and 6 mm for patients positioned in the vacuum pillow. Using an action level of 2 mm translational error, a target point correction was carried out in 4 cases. The additional workload of the described workflow compared to a normal treatment fraction led to an extra time of about 10–12 minutes, which can be further reduced by streamlining the different steps.

Conclusion

The cone beam CT attached to a LINAC allows the acquisition of a CT scan of the patient in treatment position directly before treatment. Its image quality is sufficient for determining target point correction vectors. With the presented workflow, a target point correction within a clinically reasonable time frame is possible. This increases the treatment precision, and potentially the complex patient fixation techniques will become dispensable.
Acute respiratory failure in the elderly: etiology, emergency diagnosis and prognosis
Authors: Ray Patrick , Birolleau Sophie , Lefort Yannick , Becquemin Marie-Hélène , Beigelman Catherine , Isnard Richard , Teixeira Antonio , Arthaud Martine , Riou Bruno , Boddaert Jacques
Published: May 2006

Introduction

Our objectives were to determine the causes of acute respiratory failure (ARF) in elderly patients and to assess the accuracy of the initial diagnosis by the emergency physician, and that of the prognosis.

Method

In this prospective observational study, patients were included if they were admitted to our emergency department, aged 65 years or more with dyspnea, and fulfilled at least one of the following criteria of ARF: respiratory rate at least 25 minute-1; arterial partial pressure of oxygen (PaO2) 70 mmHg or less, or peripheral oxygen saturation 92% or less in breathing room air; arterial partial pressure of CO2 (PaCO2) ≥ 45 mmHg, with pH ≤ 7.35. The final diagnoses were determined by an expert panel from the completed medical chart.

Results

A total of 514 patients (aged (mean ± standard deviation) 80 ± 9 years) were included. The main causes of ARF were cardiogenic pulmonary edema (43%), community-acquired pneumonia (35%), acute exacerbation of chronic respiratory disease (32%), pulmonary embolism (18%), and acute asthma (3%); 47% had more than two diagnoses. In-hospital mortality was 16%. A missed diagnosis in the emergency department was noted in 101 (20%) patients. The accuracy of the diagnosis of the emergency physician ranged from 0.76 for cardiogenic pulmonary edema to 0.96 for asthma. An inappropriate treatment occurred in 162 (32%) patients, and lead to a higher mortality (25% versus 11%; p < 0.001). In a multivariate analysis, inappropriate initial treatment (odds ratio 2.83, p < 0.002), hypercapnia > 45 mmHg (odds ratio 2.79, p < 0.004), clearance of creatinine < 50 ml minute-1 (odds ratio 2.37, p < 0.013), elevated NT-pro-B-type natriuretic peptide or B-type natriuretic peptide (odds ratio 2.06, p < 0.046), and clinical signs of acute ventilatory failure (odds ratio 1.98, p < 0.047) were predictive of death.

Conclusion

Inappropriate initial treatment in the emergency room was associated with increased mortality in elderly patients with ARF.
Arterial catheter-related infection of 2,949 catheters
Authors: Lorente Leonardo , Santacreu Ruth , Martín María M , Jiménez Alejandro , Mora María L
Published: May 2006

Introduction

Which particular arterial catheter site is associated with a higher risk of infection remains controversial. The Centers for Disease Control and Prevention guidelines of 1996 and the latest guidelines of 2002 make no recommendation about which site or sites minimize the risk of catheter-related infection. The objective of the present study was to analyze the incidence of catheter-related local infection (CRLI) and catheter-related bloodstream infection (CRBSI) of arterial catheters according to different access sites.

Methods

We performed a prospective observational study of all consecutive patients admitted to the 24 bed medical and surgical intensive care unit of a 650 bed university hospital during three years (1 May 2000 to 30 April 2003).

Results

A total of 2,018 patients was admitted to the intensive care unit during the study period. The number of arterial catheters, the number of days of arterial catheterization, the number of CRLIs and the number of CRBSIs were as follows: total, 2,949, 17,057, 20 and 10; radial, 2,088, 12,007, 9 and 3; brachial, 112, 649, 0 and 0; dorsalis pedis, 131, 754, 0 and 0; and femoral, 618, 3,647, 11 and 7. The CRLI incidence was significantly higher for femoral access (3.02/1,000 catheter-days) than for radial access (0.75/1,000 catheter-days) (odds ratio, 1.5; 95% confidence interval, 1.10–2.13; P = 0.01). The CRBSI incidence was significantly higher for femoral access (1.92/1,000 catheter-days) than for radial access (0.25/1,000 catheter-days) (odds ratio, 1.9; 95% confidence interval, 1.15–3.41; P = 0.009).

Conclusion

Our results suggest that a femoral site increases the risk of arterial catheter-related infection.
The gain and loss of genes during 600 million years of vertebrate evolution
Authors: Blomme Tine , Vandepoele Klaas , De Bodt Stefanie , Simillion Cedric , Maere Steven , Van de Peer Yves
Published: May 2006

Background

Gene duplication is assumed to have played a crucial role in the evolution of vertebrate organisms. Apart from a continuous mode of duplication, two or three whole genome duplication events have been proposed during the evolution of vertebrates, one or two at the dawn of vertebrate evolution, and an additional one in the fish lineage, not shared with land vertebrates. Here, we have studied gene gain and loss in seven different vertebrate genomes, spanning an evolutionary period of about 600 million years.

Results

We show that: first, the majority of duplicated genes in extant vertebrate genomes are ancient and were created at times that coincide with proposed whole genome duplication events; second, there exist significant differences in gene retention for different functional categories of genes between fishes and land vertebrates; third, there seems to be a considerable bias in gene retention of regulatory genes towards the mode of gene duplication (whole genome duplication events compared to smaller-scale events), which is in accordance with the so-called gene balance hypothesis; and fourth, that ancient duplicates that have survived for many hundreds of millions of years can still be lost.

Conclusion

Based on phylogenetic analyses, we show that both the mode of duplication and the functional class the duplicated genes belong to have been of major importance for the evolution of the vertebrates. In particular, we provide evidence that massive gene duplication (probably as a consequence of entire genome duplications) at the dawn of vertebrate evolution might have been particularly important for the evolution of complex vertebrates.
The heat sensitivity of cytokine-inducing effect of lipopolysaccharide
Authors: Gao Baochong , Wang Yun , Tsan Min-Fu
Published: May 2006

Heat inactivation by boiling has been widely used as a criterion to determine whether the observed effects of a protein preparation are a result of lipopolysaccharide (LPS) contamination. However, the heat sensitivity of LPS cytokine-inducing activity has not been characterized. In the current study, we demonstrated that the endotoxin activity, i.e., Limulus amebocyte lysate-gelating activity, and the tumor necrosis factor α (TNF-α)-inducing activity of LPS (Escherichia coli K-12 JM83, K-12 LCD25, and F583) were sensitive to boiling. Heat treatment by boiling for 15 min was sufficient to inactivate ∼90% of the LPS TNF-α-inducing activity. The heat-induced inactivation of LPS activities was not a result of adherence of boiled LPS to the wall of the container, i.e., polypropylene tubes, or aggregation of boiled LPS. In addition, boiled LPS retained its ability to bind polymyxin B. The presence of protein (ovalbumin) in LPS did not affect the heat sensitivity of LPS. Conversely, boiling reduced the size of LPS aggregates as determined by electrophoresis using native polyacrylamide gel. Likewise, the TNF-α-inducing activity of diphosphoryl lipid A (DPLA) was also sensitive to boiling. Thin-layer chromatographic analysis of boiled DPLA revealed that the heat-induced inactivation of DPLA TNF-α-inducing activity was not a result of its conversion to monophosphoryl lipid A. We conclude that the TNF-α-inducing activity of LPS and DPLA is sensitive to boiling and suggest that heat sensitivity as an indicator of whether the observed effects of a protein preparation are a result of LPS contamination should be used with caution.
Powerful Prognostic Stratification By [18F]Fluorodeoxyglucose Positron Emission Tomography in Patients With Metastatic Breast Cancer Treated With High-Dose Chemotherapy
Authors: Cachin Florent , Prince H. Miles , Hogg Annette , Ware Robert E. , Hicks Rodney J.
Published: May 2006

Purpose

This study examines the use of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the evaluation of the therapeutic response for patients treated with high-dose chemotherapy (HDC) with autologous stem cell transplantation for metastatic breast cancer (MBC) focusing on prognostic stratification.

Patients and Methods

Forty-seven patients with MBC were treated with a maximum of three cycles of HDC. Therapeutic response was assessed with conventional imaging (CImg; including a computed tomography in all cases and ultrasound, mammography, and bone scanning as clinically indicated) and by FDG-PET study performed after the last cycle of HDC. Parameters analyzed for predicting survival were FDG-PET and CImg results, pattern of disease, prior treatment, and HDC regimen.

Results

Complete responses were observed in 16 patients (37%) with CImg and 34 patients (72%) with FDG-PET. The FDG-PET result was the most powerful and independent predictor of survival; patients with a negative post-treatment FDG-PET had a longer median survival than patients with a positive FDG-PET (24 months v 10 months; P < .001). By multivariate analysis the relative risk (RR) of death was higher in patients with FDG-PET-positive disease (RR, 5.3), prior anthracycline treatment (RR, 3.3), or with visceral metastasis (RR, 2.4).

Conclusion

A single FDG-PET study performed after completion of HDC for MBC can powerfully stratify for survival. This may have implications for how we should assess outcome after conventional-dose therapy for MBC and warrants additional study.
Gene Expression and Benefit of Chemotherapy in Women With Node-Negative, Estrogen Receptor–Positive Breast Cancer
Authors: Paik Soonmyung , Tang Gong , Shak Steven , Kim Chungyeul , Baker Joffre , Kim Wanseop , Cronin Maureen , Baehner Frederick L. , Watson Drew , Bryant John , Costantino Joseph P. , Geyer Charles E. , Wickerham D. Lawrence , Wolmark Norman
Published: May 2006

Purpose

The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor–positive, lymph node–negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known.

Methods

The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy–treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS.

Results

A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (≥ 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, −1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit.

Conclusion

The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor–positive breast cancer, but also predicts the magnitude of chemotherapy benefit.
Diagnosis of Parathyroid Tumors in Familial Isolated Hyperparathyroidism with HRPT2 Mutation: Implications for Cancer Surveillance
Authors: Guarnieri Vito , Scillitani Alfredo , Muscarella Lucia Anna , Battista Claudia , Bonfitto Nazzareno , Bisceglia Michele , Minisola Salvatore , Mascia Maria Lucia , D’Agruma Leonardo , Cole David E. C.
Published: May 2006

Context: Mutations of the HRPT2 gene have recently been implicated in the development of parathyroid carcinoma.

Objective: The objective of this study was early diagnosis of parathyroid tumor in a family with germline HRPT2 mutation.

Patients, Methods, and Results: In a 40-yr-old male previously treated for parathyroid atypical adenoma, we screened the 17 translated HRPT2 exons and their exon-intron boundaries and found a germline frameshift mutation in exon 7 (685delAGAG) predicting a premature stop codon at nucleotides 767–769. Nine family members (age, 33.9 ± 19.8 yr, mean ± sd) also carry the mutation, but eight have had normal serum calcium. Biochemical and ultrasonographic evaluation uncovered a 27-yr-old hypercalcemic carrier niece with an atypical parathyroid adenoma, and a 43-yr-old normocalcemic carrier sister was found by ultrasonography to have an extrathyroidal nodule, which proved to be parathyroid carcinoma. The index case, 12 yr after surgery, was normocalcemic, but ultrasonography revealed an extrathyroidal nodule in the contralateral hemithyroid tissue that proved to be atypical adenoma.

Conclusions: Our report confirms that germline mutations of HRPT2 gene may be associated with multiple parathyroid neoplasms. Our experience suggests that longitudinal surveillance by serum biochemistry alone may not be 100% sensitive, and addition of routine neck ultrasonography is a readily accepted adjunct that may facilitate earlier disease detection in some families.
Timing of Puberty Determines Serum Insulin-Like Growth Factor-I in Late Adulthood
Authors: Sandhu Jat , Smith George Davey , Holly Jeff , Cole Tim J. , Ben-Shlomo Yoav
Published: May 2006

Context: IGFs may play an important role in disease etiology, especially cancer. Changes in diet can alter acute levels, but little is known about life course influences on IGF levels.

Objective: The objective of the study was to examine the association between timing of puberty and adulthood serum IGFs (IGF-I and IGF binding protein-3).

Design: This was a retrospective cohort study.

Setting: Male pupils who attended a single school in Southern England were part of the study.

Participants: Participants in the study were a cohort of 1028 men born between 1927 and 1956 with anthropometric measures between 9 and 18 yr and adulthood serum IGF levels.

Main Outcome Measure: The study measured serum IGF-I and IGF binding protein-3 at mean age 63 yr.

Results: Age at peak height velocity (APHV) was inversely associated with adult IGF-I levels. IGF-I decreased by 3.7 ng/ml (95% confidence interval 1.0–6.4, P = 0.007) for each sd increase in APHV. Prepubertal childhood height and body mass index were both inversely associated with APHV (P trend < 0.001). APHV was positively associated with adult height and inversely associated with adult body mass index. Adjustment for childhood, adult anthropometry, and other lifestyle factors did not substantially alter the association between APHV and adult IGF-I.

Conclusions: This is the first study to document an association between timing of puberty and adult IGF-I levels. A better understanding of life course determinants of the IGF system may provide new insights into disease etiology and primary prevention.
Laparoscopic Adrenalectomy for Potentially Malignant Adrenal Tumors Greater than 5 Centimeters
Authors: Liao Chun-Hou , Chueh Shih-Chieh , Lai Ming-Kuen , Hsiao Po-Jen , Chen Jun
Published: May 2006

Purpose: Laparoscopic adrenalectomy (LA) is controversial for large, potentially malignant tumors. We report a series of LA or hand-assisted LA for large (>5 cm) adrenal tumors.

Patients and Methods: Among 210 LAs performed in 6 yr, 39 patients had potentially malignant tumors greater than 5 cm in diameter. Their perioperative and follow-up data were retrospectively analyzed.

Results: All 39 patients had successful LAs without perioperative mortality, conversion to open surgery, or capsular disruption during dissection. The mean tumor size was 6.2 cm (range, 5–12 cm), operative time 207 min (115–315 min), and blood loss 75 ml (minimal–1400 ml). Complications included one intraoperative diaphragmatic perforation, three mild wound infections, and one pneumonia. Preoperatively there were 27 nonfunctioning tumors, seven pheochromocytomas, three cortisol-secreting tumors, and two virilizing tumors. Final pathology revealed eight malignant (four adrenocortical carcinomas and four metastatic carcinomas) and 31 benign tumors (14 cortical adenomas, eight pheochromocytomas, six myelolipomas, and three ganglioneuromas). Median follow-up was 39 months. Four patients (two adrenocortical carcinomas, one metastatic hepatoma, and one lymphoma) died 24, 10, 9, and 3 months after surgery, respectively. A hand-assisted device was used in 10 patients. Only the tumor size was larger and length of postoperative hospital stay longer for those in the hand-assisted group.

Conclusions: LA is a reasonable option for selected large adrenal tumors when complete resection is technically feasible and there is no evidence of local invasion. Hand-assisted LA is a good alternative to open conversion if a difficult dissection is encountered intraoperatively.
Ghrelin and Peptide YY in Youth: Are There Race-Related Differences?
Authors: Bacha Fida , Arslanian Silva A.
Published: May 2006

Objective: Obesity prevalence is higher in African-American (AA) vs. American white (AW) youth. Ghrelin is a “hunger” peptide that is high preprandially and decreases postprandially, and peptide YY (PYY) is a “satiety” hormone increasing after meals. Impaired regulation of ghrelin/PYY may be conducive to obesity. We hypothesized that racial differences in childhood obesity could partly be explained by differences in ghrelin/PYY dynamics.

Research Design and Methods: We investigated: 1) ghrelin suppression/PYY elevation in response to an oral glucose tolerance test (OGTT) in AA vs. AW, and 2) the relationship of ghrelin and PYY dynamics to insulin sensitivity. Thirty-three AA and 54 AW prepubertal children underwent an OGTT measuring ghrelin, PYY, glucose, and insulin. Fasting glucose to insulin ratio (GF/IF) was used to assess the relationship of insulin sensitivity to fasting and post-OGTT ghrelin and PYY levels.

Results: OGTT-induced suppression in ghrelin (Δ ghrelin) was lower in AA youth. Δ ghrelin correlated with GF/IF (r = 0.47, P < 0.001) and Δ insulin at 30 min (r = −0.47, P < 0.001). In multiple regression analysis, race (P = 0.013) and GF/IF (P = 0.004) contributed independently to the variance in Δ ghrelin (R2 = 0.28, P < 0.001). Fasting and post-OGTT PYY levels were lower in AAs and were not related to insulin sensitivity.

Conclusion: The lower suppression of ghrelin in AA, but not the lower PYY levels, correlates with insulinemia and insulin resistance. Less ghrelin suppression and PYY elevation after a meal in black youth could be a potential mechanism of race-related differences in hunger/satiety predisposing to risk of obesity.
Syndromic Obesity and Diabetes: Changes in Body Composition with Age and Mutation Analysis of ALMS1 in 12 United Kingdom Kindreds with Alström Syndrome
Authors: Minton J. A. L. , Owen K. R. , Ricketts C. J. , Crabtree N. , Shaikh G. , Ehtisham S. , Porter J. R. , Carey C. , Hodge D. , Paisey R. , Walker M. , Barrett T. G.
Published: May 2006

Context: Alström syndrome (AS) is a monogenic form of infancy-onset obesity and insulin resistance, caused by ALMS1 mutations. The natural history of the insulin resistance is unknown, in particular how this relates to changes in body composition. It is also unclear how ALMS1 mutations relate to the characteristic phenotype.

Objectives: Our objectives were to characterize body composition and metabolic parameters, to establish ALMS1 mutation spectrum of United Kingdom AS patients, and to determine whether a genotype-phenotype correlation exists.

Design and Patients: We conducted a cross-sectional cohort study of 12 unrelated subjects with AS. Age-standardized body composition was assessed by anthropometry and dual-energy x-ray absorptiometry and insulin sensitivity by homeostasis model assessment. The exons and intron-exon boundaries of ALMS1 were directly sequenced.

Setting: The study was performed during the annual Alström Syndrome UK multidisciplinary screening clinic.

Results: AS patients have early-onset obesity, but body mass index, waist circumference, and body fat from dual-energy x-ray absorptiometry were negatively correlated with age (r = −0.37, P = 0.2; r = −0.84, P = 0.002; and r = −0.6, P = 0.05). Despite this, insulin resistance increased, demonstrated by raised fasting insulin and fall in homeostasis model assessment insulin sensitivity with age (r = −0.64, P = 0.02). ALMS1 mutations were identified in 10 of 12 patients, with a potential founder mutation in exon 16 present in five [np 10775del (C); Del3592fs/ter3597]. No genotype-phenotype correlation was observed.

Conclusions: We identified mutations in ALMS1 in more than 80% of patients with no genotype-phenotype correlation. In AS, severe childhood obesity, waist circumference, and body fat decrease with age, whereas insulin resistance increases. The abdominal obesity, insulin resistance, diabetes, hypertriglyceridemia, and hypertension suggest that AS could represent a monogenic model for the metabolic syndrome.
Self-Esteem and Social Adjustment in Young Women with Turner Syndrome—Influence of Pubertal Management and Sexuality: Population-Based Cohort Study
Authors: Carel Jean-Claude , Elie Caroline , Ecosse Emmanuel , Tauber Maïthé , Léger Juliane , Cabrol Sylvie , Nicolino Marc , Brauner Raja , Chaussain Jean-Louis , Coste Joël
Published: May 2006

Context: Pediatric management of patients with Turner syndrome focuses on height, frequently resulting in a delay of pubertal induction. The influence of pubertal management on psychosocial adjustment and sex life has not been evaluated in Turner syndrome patients.

Objective: The objective of the study was to identify the determinants of self-esteem, social adjustment, and initiation of sex life in patients with Turner syndrome, particularly those related to pubertal management.

Design: This was a prospective evaluation, the StaTur study.

Setting: The study was conducted with a population-based registry of GH-treated patients.

Participants: Participants included 566 young adult women with Turner syndrome, aged 22.6 ± 2.6 yr (range, 18.3–31.2).

Main Outcome Measures: Measures used in the study were Coopersmith’s Self-Esteem Inventory, Social Adjustment Scale Self-Report, questions on sexual experience, and extensive data on pediatric management.

Results: Low self-esteem was associated with otological involvement and limited sexual experience. Low social adjustment was associated with lower paternal socioeconomic class and an absence of sexual experience. Late age at first kiss or date was associated with cardiac involvement and a lack of spontaneous pubertal development. Age at first sexual intercourse was related to age at puberty and paternal socioeconomic class. Delayed induction of puberty had a long-lasting effect on sex life. Height and height gain due to GH treatment had no effect on outcomes.

Conclusions: Puberty should be induced at a physiologically appropriate age in patients with Turner syndrome to optimize self-esteem, social adjustment, and initiation of the patient’s sex life. Therapeutic interventions altering normal pubertal development in other groups of patients should be reconsidered in light of these findings.
Increased Anti-Müllerian Hormone Serum Concentrations in Prepubertal Daughters of Women with Polycystic Ovary Syndrome
Authors: Sir-Petermann Teresa , Codner Ethel , Maliqueo Manuel , Echiburú Bárbara , Hitschfeld Catalina , Crisosto Nicolás , Pérez-Bravo Francisco , Recabarren Sergio E. , Cassorla Fernando
Published: May 2006

Context: Anti-Müllerian hormone (AMH) is produced by the granulosa cells and reflects follicular development. Adult women with polycystic ovary syndrome (PCOS) have increased levels of AMH associated with an excessive number of growing follicles. However, it is not known whether these abnormalities are present before the clinical onset of PCOS.

Objective: Our objective was to investigate whether prepubertal daughters of women with PCOS have increased AMH levels.

Design: Fourteen female infants (2–3 months old) and 25 prepubertal girls (4–7 yr old) born to PCOS mothers were studied. As a control group, we studied 21 female infants and 24 prepubertal girls born to mothers with regular menses and without hyperandrogenism. The group with PCOS mothers and the control group had normal birth weight and were born from spontaneous singleton pregnancies. Circulating concentrations of gonadotropins, testosterone, androstenedione, estradiol, 17-OH-progesterone, SHBG, inhibin B, and AMH were determined by specific assays.

Results: Serum concentrations of AMH were significantly higher in the PCOS group compared with the control group during early infancy (20.4 ± 15.6 vs. 9.16 ± 8.6 pmol/liter; P = 0.024) and during childhood (14.8 ± 7.7 vs. 9.61 ± 4.4 pmol/liter; P = 0.007). Gonadotropin and serum sex steroid concentrations were similar in both groups during the two study periods, except for FSH, which was lower during childhood in girls born to PCOS mothers.

Conclusions: We conclude that serum AMH concentrations are increased in prepubertal daughters of PCOS women, suggesting that these girls appear to show evidence of an altered follicular development during infancy and childhood.
Serum Profiles of Free and Conjugated Neuroactive Pregnanolone Isomers in Nonpregnant Women of Fertile Age
Authors: Havlíková Helena , Hill Martin , Kancheva Lyudmila , Vrbíková Jana , Pouzar Vladimír , Černý Ivan , Kancheva Radmila , Stárka Luboslav
Published: May 2006

Background: Pregnanolone isomers (PI) with a hydroxy group in the 3α-position are neuroinhibitors operating via positive modulation of GABAA receptors. The 3β-PI and sulfates of PI and pregnenolone exert the opposite effect. In addition to the brain’s in situ synthesis, some circulating steroids can penetrate the blood-brain barrier.

Methods: To assess the physiological impact of peripheral endogenous neuroactive pregnanolone isomers and their polar conjugates in women, serum allopregnanolone (P3α5α), isopregnanolone (P3β5α), pregnanolone (P3α5β), epipregnanolone (P3β5β), pregnenolone, estradiol (including their polar conjugates), and additional steroids were measured in 16 women in the follicular and luteal phases of the menstrual cycle using gas chromatography/mass spectrometry and RIA for the analysis. Linear models and Spearman’s correlations were used for data evaluation.

Results and Discussion: The levels of conjugated PI were from one to almost three orders of magnitude higher in comparison with the free steroids. The results indicate that a substantial proportion of the progesterone is metabolized in the sequence progesterone→5β-dihydroprogesterone→P3α5β→conjugated P3α5β. The sulfation of PI and particularly of P3α5β moderates the levels of free PI and restrains estradiol biosynthesis via progesterone degradation. PI including the conjugates reflected changing progesterone formation during the menstrual cycle. In the follicular phase, the positive correlation with conjugated pregnenolone, the independence of progesterone, and the negative age relationships of PI indicate their adrenal origin. The dependence on progesterone and the independence of conjugated pregnenolone suggest a gonadal source of PI in the luteal phase. The neuroactivating PI prevailed over neuroinhibiting PI.
Effect of Long-Term Calorie Restriction with Adequate Protein and Micronutrients on Thyroid Hormones
Authors: Fontana Luigi , Klein Samuel , Holloszy John O. , Premachandra Bhartur N.
Published: May 2006

Context: Caloric restriction (CR) retards aging in mammals. It has been hypothesized that a reduction in T3 hormone may increase life span by conserving energy and reducing free-radical production.

Objective: The objective of the study was to assess the relationship between long-term CR with adequate protein and micronutrient intake on thyroid function in healthy lean weight-stable adult men and women.

Design, Setting, and Participants: In this study, serum thyroid hormones were evaluated in 28 men and women (mean age, 52 ± 12 yr) consuming a CR diet for 3–15 yr (6 ± 3 yr), 28 age- and sex-matched sedentary (WD), and 28 body fat-matched exercising (EX) subjects who were eating Western diets.

Main Outcome Measures: Serum total and free T4, total and free T3, reverse T3, and TSH concentrations were the main outcome measures.

Results: Energy intake was lower in the CR group (1779 ± 355 kcal/d) than the WD (2433 ± 502 kcal/d) and EX (2811 ± 711 kcal/d) groups (P < 0.001). Serum T3 concentration was lower in the CR group than the WD and EX groups (73.6 ± 22 vs. 91.0 ± 13 vs. 94.3 ± 17 ng/dl, respectively) (P ≤ 0.001), whereas serum total and free T4, reverse T3, and TSH concentrations were similar among groups.

Conclusions: Long-term CR with adequate protein and micronutrient intake in lean and weight-stable healthy humans is associated with a sustained reduction in serum T3 concentration, similar to that found in CR rodents and monkeys. This effect is likely due to CR itself, rather than to a decrease in body fat mass, and could be involved in slowing the rate of aging.