Risk factors for residual fibroglandular breast tissue following a mastectomy - an overview and retrospective cohort study.

BACKGROUND: Residual fibroglandular breast tissue (RFGT) following a mastectomy is associated with the remaining of occult breast cancer at the time of mastectomy as well as an increased local recurrence risk thereafter. Despite its oncologic implications, data on measures to prevent RFGT are lacking. Therefore, in a first step knowledge of risk factors for RFGT is of uttermost importance in order to allow identification of patients at risk and subsequently adaption of the surgical treatment and potentially prevention of RFGT a priori. METHODS: We performed a systematic literature review in PubMed using the MESH terms [residual fibroglandular breast tissue], [residual breast tissue], [mastectomy] and [risk factor] followed by a retrospective data analysis including all patients with a mastectomy treated at the Department of Obstetrics and Gynecology of the Medical University of Vienna, Austria, between 01.01.2015 and 26.02.2020 in order to identify risk factors of RFGT following a mastectomy. The primary aim of the study was to assess a potential difference in RFGT volume between the different types of mastectomy. The secondary objectives of the study were to identify other potential risk factors for RFGT as well as to compare the skin and subcutaneous fat tissue thickness pre- to postoperatively. RESULTS: Significantly higher RFGT volumes were observed following a nipple-sparing mastectomy (NSM) compared to a skin-sparing mastectomy (SSM) and radical mastectomy (RME) (p < .001). Furthermore, RFGT volume was significantly associated with the variables: reconstruction (p = .012), acellular dermal matrix (ADM) or mesh (p = .031), patient age (p = .022), preoperative fibroglandular tissue (FGT) volume (p = .012) and preoperative whole breast volume (including the skin envelope and nipple-areola-complex) (p = .030). The reduction in the postoperative compared to preoperative skin envelope thickness measured medially and laterally reached statistical significance in the NSM-cohort (medial p < .001, lateral p = .001) and showed a numerical difference in the RME and SSM-cohort. CONCLUSION: Mastectomy type, reconstruction, ADM or mesh, patient age, preoperative FGT volume and whole breast volume were identified as risk factors for RFGT in univariable analysis. The observed reduction in the post- compared to preoperative skin envelope thickness should be avoided considering the known associated increase in risk for ischemic complications.

Multiple breath washout in pediatric patients after lung transplantation.

Forced expiratory volume in 1 second (FEV1 ) from spirometry is the most commonly used parameter to detect early allograft dysfunction after lung transplantation (LTx). There are concerns regarding its sensitivity. Nitrogen-multiple breath washout (N2 -MBW) is sensitive at detecting early global (lung clearance index [LCI]) and acinar (Sacin ) airway inhomogeneity. We investigated whether N2 -MBW indices indicate small airways pathology after LTx in children with stable spirometry. Thirty-seven children without bronchiolitis obliterans syndrome [BOS] at a median of 1.6 (0.6-3.0) years after LTx underwent N2 -MBW and spirometry, 28 of those on 2 occasions (≤6 months apart) during clinically stable periods. Additional longitudinal data (11 and 8 measurements, respectively) are provided from 2 patients with BOS. In patients without BOS, LCI and Sacin were significantly elevated compared with healthy controls. LCI was abnormal at the 2 test occasions in 81% and 71% of patients, respectively, compared with 30% and 39% of patients with abnormal FEV1 /forced vital capacity (FVC). Correlations of LCI with FEV1 /FVC (r = 0.1, P = .4) and FEV1 (r = -0.1, P = .6) were poor. N2 -MBW represents a sensitive and reproducible tool for the early detection of airways pathology in stable transplant recipients. Moreover, indices were highly elevated in both patients with BOS. Spirometry and LCI showed poor correlation, indicating distinct and complementary physiologic measures.

Changes in breathing pattern upon 100% oxygen in children at early school age.

Nitrogen multiple-breath washout (N2MBW) is an increasingly used tidal breathing test in young children to assess ventilation inhomogeneity. However, the test requires 100% oxygen to perform. We aimed to examine the potential influence of pure oxygen on breathing pattern in school-aged children. We performed tidal breathing measurements under room air followed by N2MBW in 16 former preterm children and 24 healthy controls. We compared tidal volume (VT), coefficient of variation of VT (CVVT), respiratory rate (RR), and minute ventilation (VE) between tidal breathing and N2MBW, and between the start and end of tidal breathing. Mean (range) age was 6.8 (5.9, 9.0) years. VT, RR and VE showed no significant change upon oxygen-exposure, while CVVT significantly decreased by 5% (95% CI: 1.2, 9.0; p=0.012). However CVVT was also the only parameter which significantly decreased during tidal breathing. Overall, pure oxygen has no systematic effect on breathing pattern in young school-aged children. N2MBW can reliably be used as tracer gas in this age group.

Paget's disease of bone: an endocrine society clinical practice guideline

OBJECTIVE: The aim of this guideline was to formulate practice guidelines for the diagnosis and treatment of Paget's disease of the bone. PARTICIPANTS: The guideline was developed by an Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer. EVIDENCE: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. CONSENSUS PROCESS: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Two systematic reviews were conducted to summarize supporting evidence. CONCLUSIONS: We recommend that plain radiographs be obtained of the pertinent regions of the skeleton in patients with suspected Paget's disease. If the diagnosis is confirmed, we suggest that a radionucleotide bone scan be done to determine the extent of the disease. After diagnosis of Paget's disease, we recommend measurement of serum total alkaline phosphatase or, when warranted, a more specific marker of bone formation or bone resorption to assess the response to treatment or evolution of the disease in untreated patients. We suggest treatment with a bisphosphonate for most patients with active Paget's disease who are at risk for future complications. We suggest a single 5-mg dose of iv zoledronate as the treatment of choice in patients who have no contraindication. In patients with monostotic disease who have a normal serum total alkaline phosphatase, we suggest that a specific marker of bone formation and bone resorption be measured, although these may still be normal. Serial radionuclide bone scans may determine the response to treatment if the markers are normal. We suggest that bisphosphonate treatment may be effective in preventing or slowing the progress of hearing loss and osteoarthritis in joints adjacent to Paget's disease and may reverse paraplegia associated with spinal Paget's disease. We suggest treatment with a bisphosphonate before surgery on pagetic bone.(AU)

Exhaled nitric oxide in symptomatic children at preschool age predicts later asthma.

BACKGROUND: Prediction of asthma in young children with respiratory symptoms is hampered by the lack of objective measures applicable in clinical routine. In this prospective study in a preschool children cohort, we assessed whether the fraction of exhaled nitric oxide (FeNO), a biomarker of airway inflammation, is associated with asthma at school age. METHODS: At baseline, IgE and eosinophils were measured in the blood, and FeNO was measured offline in 391 children aged 3-47 months with lower airway symptoms. We developed an asthma predictive index (API) including high FeNO as major criterion. At follow-up, primary outcome was physician-diagnosed asthma based on standardized interviews in those children reaching school age (n = 166). RESULTS: FeNO was significantly elevated in those children with later asthma (68/166) as compared to children not developing asthma. Median (IQR) FeNO was 10.5 (6.6-17.2) vs. 7.4 (5.3-10.3) ppb. Per 5 ppb FeNO increase, the odds ratio (95% CI) for asthma increased by 2.44 (1.61-3.70) without changing when adjusting for confounders. Using the new API, children scored at risk had 58.0% probability for later asthma, whereas the negative predictive value was 78.2%, which was comparable to the classical API. CONCLUSIONS: In this cohort of high-risk preschool children, elevated FeNO is associated with increased risk for school-age asthma. The new API including FeNO identifies children at risk of later asthma comparably to the classical API, but does not require blood sampling.

Normative data for lung function and exhaled nitric oxide in unsedated healthy infants.

Despite association with lung growth and long-term respiratory morbidity, there is a lack of normative lung function data for unsedated infants conforming to latest European Respiratory Society/American Thoracic Society standards. Lung function was measured using an ultrasonic flow meter in 342 unsedated, healthy, term-born infants at a mean ± sd age of 5.1 ± 0.8 weeks during natural sleep according to the latest standards. Tidal breathing flow-volume loops (TBFVL) and exhaled nitric oxide (eNO) measurements were obtained from 100 regular breaths. We aimed for three acceptable measurements for multiple-breath washout and 5-10 acceptable interruption resistance (R(int)) measurements. Acceptable measurements were obtained in ≤ 285 infants with high variability. Mean values were 7.48 mL·kg⁻¹ (95% limits of agreement 4.95-10.0 mL·kg⁻¹) for tidal volume, 14.3 ppb (2.6-26.1 ppb) for eNO, 23.9 mL·kg⁻¹ (16.0-31.8 mL·kg⁻¹) for functional residual capacity, 6.75 (5.63-7.87) for lung clearance index and 3.78 kPa·s·L⁻¹ (1.14-6.42 kPa·s·L⁻¹) for R(int). In males, TBFVL outcomes were associated with anthropometric parameters and in females, with maternal smoking during pregnancy, maternal asthma and Caesarean section. This large normative data set in unsedated infants offers reference values for future research and particularly for studies where sedation may put infants at risk. Furthermore, it highlights the impact of maternal and environmental risk factors on neonatal lung function.

Longitudinal monitoring of pediatric cystic fibrosis lung disease using nitrite in exhaled breath condensate.

Cystic fibrosis (CF) lung disease is characterized by airway inflammation and airway infection. Nitrites in exhaled breath condensate (EBC-NO(2)(-)) have been shown to be increased in children and adults with CF compared to healthy controls suggesting its use as a measure of airway inflammation. This longitudinal study aimed to evaluate if repeated measurements of EBC-NO(2)(-) are helpful in monitoring CF lung disease activity in children. Thirty-two children with mild CF lung disease (age 10.6 +/- 3.3 years) were recruited in two study centers. Follow-up visits occurred every 3 months over a period of 1 year with a total of five visits. Each visit included a clinical assessment incorporating a modified Shwachman-Kulczycki (SK) score, spirometry, an oropharyngeal swab, or sputum sample for bacterial analysis and an EBC sample analyzed for NO(2)(-) using a spectrophotometric assay. Furthermore at the first and the last visit a chest radiograph was done and scored (Chrispin-Norman (CN) score). There was no correlation of EBC-NO(2)(-) and parameters of spirometry, SK-score, or CN-score. Furthermore, increased EBC-NO(2)(-) levels did not predict subsequent pulmonary exacerbations. We conclude that repeated measurements of EBC-NO(2)(-) are not helpful in the longitudinal monitoring of mild CF lung disease in children.

Predicting factors for severity of rheumatoid arthritis: a prospective multicenter cohort study of 172 patients over 3 years.

Rheumatoid arthritis may take an unfavourable course leading to rapid functional decline in a certain percentage of patients. Early identification of these patients is desirable. The aim of this study was to evaluate clinical and laboratory parameters for their value in the prediction of bad outcome. A total of 172 patients with early arthritis were followed for 3 years. Higher initial values for erythrocyte sedimentation rate, IgG and IgM rheumatoid factor, serum concentration of cartilage oligomeric matrix protein, Health Assessment Questionnaire score, Larsen score of feet, disease activity score, and swollen and tender joint count predicted worse outcome. An association with the presence of IgA rheumatoid factor or anti-cyclic-citrullinated peptide could not be established. We conclude that prognosis in an individual with rheumatoid arthritis depends on many factors. The determination of independent prognostic factors for progression of rheumatoid arthritis is a valuable tool in early arthritis to select patients for more aggressive therapy.

Death in correctional facilities: opportunities for automated external defibrillation.

BACKGROUND: Death due to cardiovascular disease occurs more frequently in prisons than the national average. Due to close surveillance 24 h/day, the ability to reach the patient within 3 min and time consuming access for the EMS crews, it was hypothesised that the deployment of automated external defibrillators (AEDs) might make improvements regarding Call-to-the-First-AED-Prompt (CTP) interval and formed the aim of this study. METHODS: Our investigation was analysed on an intention to treat basis and conducted in a prospective, open and observational design. As the primary outcome, the CTP-intervals were compared to the arrival intervals of the EMS. As a secondary outcome, an analysis of all deceased inmates was described. RESULTS: The average daily population of inmates in Austrian correctional facilities is 7714. During a period of 13 months, 10 instances in which an AED was activated and electrodes attached to a collapsed inmate, were reported. The CTP-interval (median+/-S.D.) was 2.3+/-1.6 S.D. min. It took the EMS 10.0+/-4.3 S.D. min. to arrive at the patient's side. Four out of 10 cases of cardiac arrest occurred due to myocardial infarction. Of 39 deceased inmates, a post mortem examination was completed in 34 cases. In 13 cases, cardiovascular disease was the cause of death. DISCUSSION: The main finding was a four-fold reduction of the CTP-interval. This fact indicates the potential improvements which could be achieved with the deployment of AEDs. Our secondary objective revealed that death due to cardiovascular disease was found in a high proportion and could be considered to be a strong incentive to initiate programmes to counter cardiovascular death in prison.

[Treatment of osteoarthritis of the knee joint. Efficacy and tolerance to acemetacin slow release in comparison to celecoxib]. / Behandlung der Gonarthrose. Wirksamkeit und Verträglichkeit von retardiertem Acemetacin im Vergleich zu Celecoxib.

OBJECTIVE: The aim of this trial was to compare acemetacin (ACE) with celecoxib (CEL) in terms of tolerability and efficacy in the treatment of osteoarthritis of the knee joint. METHODS: A total of 105 patients (26-64 years old) suffering from primary osteoarthritis (OA) of the knee were enrolled in this international, multicenter, randomized, double blind controlled trial. Fifty three patients were given ACE and 52 CEL. They were treated with either 90 mg bid of slow release ACE or 200 mg bid of CEL for 6 weeks. Additional gastroprotective therapy was not provided. Tolerability was assessed by physical examination, laboratory tests, vital signs and reports of side effects, as well as by patient and physician global assessments. Efficacy parameters comprised pain assessment by visual analogue scale (VAS) and ordinal scale, WOMAC, SF-36 and patient and physician global impressions of efficacy. In addition, acetaminophen consumption was recorded. RESULTS: In 21 ACE (39.6%) and 19 CEL patients (36.5%), the number of side effects totaled 56 (ACE n=29; CEL n=27) (ns). Mean pain reduction at week 6 was highly significant ( P<0.0001) in both groups and amounted to 38.7 mm (+/-20.3) in the ACE group and to 35.1 mm (+/-18.7) in the CEL group (ns). Very similar results were seen with respect to the other efficacy parameters. CONCLUSION: ACE is not inferior to CEL for the short-term treatment of knee OA in terms of tolerability and efficacy.

Comparison of the efficacy and tolerability of dexibuprofen and celecoxib in the treatment of osteoarthritis of the hip.

CONTEXT: Osteoarthritis (OA) is often treated with nonsteroidal anti-inflammatory drugs (NSAIDs) or selective inhibitors of cyclooxygenase-2 (COX-2). OBJECTIVE: This clinical trial aimed to assess directly the relative therapeutic efficacy of the isolated active enantiomer of ibuprofen, named dexibuprofen (S(+)-ibuprofen) in a special crystal form, and the selective COX-2 inhibitor celecoxib in adults with OA of the hip. Moreover, the hypothesis that the tolerability/safety profile of dexibuprofen is comparable to celecoxib is to be tested. METHODS: The investigation was a randomized, parallel-group, double-blind, active controlled clinical trial, conducted from January 2001 to February 2002 in 4 rehabilitation centers in Austria. 148 inpatients were randomly assigned to dexibuprofen 800 mg or celecoxib 200 mg daily. The primary criterion was the improvement in the Western Ontario and' McMasters osteoarthritis index (WOMAC OA index) after 15 days of therapy. RESULTS: Evaluation of the WOMAC OA index proved that dexibuprofen 400 mg b.i.d. is not inferior to celecoxib 100 mg b.i.d. with the Mann-Whitney estimator equal to 0.5129 and the corresponding lower boundary of the 95% confidence interval equal to 0.4409. The overall incidence of adverse drug reactions was 12.16% in the dexibuprofen group and 13.51% in the celecoxib group. 8.1% of patients on dexibuprofen and 9.5% on celecoxib suffered from gastrointestinal disorders. CONCLUSION: In the presented clinical trial dexibuprofen has at least equal efficacy and a comparable safety/tolerability profile as celecoxib in adult patients suffering from osteoarthritis of the hip.

[Functional capacity and cartilage oligomeric protein (COMP) in serum of patients with maturity-onset polyarthritis]. / Funktionelle Kapazität und Cartilage Oligomeric Matrix Protein (COMP) im Serum bei Patienten mit Alterspolyarthritis.

OBJECTIVE: To compare late onset with adult onset rheumatoid arthritis. METHODS: Fifty-eight patients with late onset rheumatoid arthritis (LORA) were compared to 117 patients with adult onset rheumatoid arthritis (AORA) with respect to clinical and functional parameters. Furthermore, in 104 patients serum cartilage oligomeric matrix protein (COMP) was measured. Results were compared by means of ANOVA and possible influences of age, gender and clinical parameters were evaluated by Spearman rank correlation. RESULTS: Except a different distribution in gender (40% males in the LORA group) and a higher ESR, no differences could be found with respect to clinical parameters. However, a significantly higher HAQ score and significantly higher serum-COMP levels could be shown in the LORA group. HAQ scores correlated not only with disease activity parameters (C-reactive protein, disease activity score) but also with the age. Serum-COMP levels did show a correlation with the age as well, but not with disease activity. CONCLUSION: It is concluded that the higher serum-COMP levels in late onset rheumatoid arthritis could be due to concomitant osteoarthritic processes in larger joints, which are not symptomatic. The age dependence of the HAQ score is only weak, but may be the reason why patients with LORA show a worse functional capacity compared to patients with adult onset rheumatoid arthritis.

A urine midmolecule osteocalcin assay shows higher discriminatory power than a serum midmolecule osteocalcin assay during short-term alendronate treatment of osteoporotic patients.

We isolated and characterized a peptide fragment corresponding to amino acid sequence 14-28 of human osteocalcin in urine from Paget's disease, and developed a polyclonal antibody reactive to this peptide in urine. We used this antibody to measure urinary fragments of osteocalcin and compared to efficacy of the urinary osteocalcin assay with a serum osteocalcin (sOC) assay (ELISA-Osteo, Cis-Bio International) to monitor the short-term changes in bone turnover in response to alendronate treatment. The synthetic peptide-based urinary osteocalcin (uOC) radioimmunoassay (RIA) showed an analytical sensitivity of 6.25 ng/mL, standard curve range of 3.12-400 ng/mL, and mean intra- (n = 20) and interassay (n = 30) coefficient of variation (CV) of <15%. Urine osteocalcin concentrations in postmenopausal osteoporotic patients were approximately 90% higher than in normal premenopausal controls. Series of 24 h urine and matched serum samples were collected at baseline, 30 days, and 90 days after treatment of postmenopausal osteoporotic patients with daily dose of 10 mg alendronate. We measured urinary osteocalcin (uOc) levels and urinary N-telopeptide (uNTx, Ostex) in urine samples and serum N-telopeptide (sNTx), C-telopeptide (sCTx, Osteometer), serum osteocalcin (sOC) as well as bone-specific alkaline phosphatase (sALP) (Alkphose-B, Metra Biosystems) in serum samples. The percent change data obtained between baseline and 30 days (n = 18) posttreatment suggested a rapid decline in uOC concentration (-27%, p < 0.01) in response to alendronate treatment, as compared with a marginal and nonsignificant decrease in sOC (-7.2%, p = 0.417) or sALP (-3.4%, p = 0.689), two specific markers of bone formation. As expected, due to the coupling of bone formation and bone resorption, the concentration of all markers showed a 30%-45% decline compared with baseline values after 90 days (n = 16) of treatment. Correlation of markers after a 30 day treatment with alendronate revealed a higher correlation (r = 0.61, p < 0.01) between uOC and uNTx, as compared with sOC (r = 0.03, p = 0.447) or sALP (r = -0.14, p = 0.295) with uNTx. Similarly, correlation coefficients with r values between 0.48 and 0.55 (p < 0.05) were observed between uOC, sNTx, and sCTx, whereas no significant correlation was observed between sOC and sNTx or sCTx. These results provide indirect evidence that fragments measured by the urine assay probably originated from bone resorption, and suggest that the uOC assay could be used to assess short-term changes in bone metabolism with regard to osteocalcin.

Albers-Schönberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene.

Albers-Schönberg disease, or autosomal dominant osteopetrosis, type II (ADO II), is the most common form of osteopetrosis, a group of conditions characterized by an increased skeletal mass due to impaired bone and cartilage resorption. Following the assignment of the gene causing ADO II to chromosome 16p13.3, we now report seven different mutations in the gene encoding the ClCN7 chloride channel in all 12 ADO II families analysed. Additionally, a patient with the severe, autosomal recessive, infantile form of osteopetrosis (ARO) was identified as being homozygous for a ClCN7 mutation. From genotype-phenotype correlations, it seems that ADO II reflects a dominant negative effect, whereas loss-of-function mutations in ClCN7 do not cause abnormalities in heterozygous individuals. Because some ARO patients have mutations in both copies of the ClCN7 gene, ADO II is allelic with a subset of ARO cases.

Long-term management and outcome of parathyroidectomy for sporadic primary multiple-gland disease.

HYPOTHESIS: For a specific subset of patients with sporadic primary multiple-gland parathyroid disease, subtotal parathyroidectomy results in long-term normocalcemia in the majority of patients, with a minimal complication rate. DESIGN: Retrospective analysis of outcomes in patients undergoing parathyroidectomy performed by a single surgeon (A.E.G.) between 1984 and 1999. SETTING: A multidisciplinary endocrine service based at a tertiary referral center. PATIENTS: Patients undergoing subtotal parathyroidectomy for primary hyperparathyroidism due to sporadic multiple-gland disease identified from a single surgeon's operative records (A.E.G.). MAIN OUTCOME MEASURES: Data analyzed included demographic factors, operative and pathologic findings, and postoperative and long-term clinical and laboratory results, including calcium and intact parathyroid hormone levels. RESULTS: Of 379 patients undergoing parathyroidectomy for hyperparathyroidism between 1984 and 1999, 49 (13%) had sporadic multiple-gland disease. Median preoperative calcium and intact parathyroid hormone (iPTH) levels were 2.7 mmol/L (10.8 mg/dL) and 11.79 pmol/L, respectively. Postoperative calcium and iPTH levels were available in 39 patients, and median values were 2.28 mmol/L (9.1 mg/dL) and 2.84 pmol/L, respectively. Long-term follow-up was available for 36 patients (73%), and duration ranged from 6 to 180 months (median, 44 months). Median calcium and iPTH levels at follow-up were 2.3 mmol/L (9.2 mg/dL) and 3.26 pmol/L, respectively, with 3 (8%) of 36 patients having evidence of persistent or recurrent hyperparathyroidism. No patient had biochemical evidence of hypoparathyroidism at long-term follow-up. Five patients (14%) had persistent elevated iPTH levels (range, 8.11-10.95 pmol/L) and normal calcium levels. CONCLUSIONS: Subtotal parathyroidectomy for sporadic primary multiple-gland disease resulted in a long-term normocalcemia rate of 92%, with minimal complications. Selective subtotal parathyroidectomy can yield excellent long-term results in patients with multiple-gland disease.

Bisphosphonate treatment inhibits the growth of prostate cancer cells.

The presence of skeletal metastases in patients suffering from cancer leads to a variety of clinical complications. Bisphosphonates are a class of drugs with a potent bone resorption inhibition activity that have found increasing utility in treating and managing patients with metastatic bone disease. Several clinical trials have demonstrated that bisphosphonates have clinical value in the treatment and management of skeletal metastases derived from advanced prostate cancer. Currently, the mechanism(s) through which bisphosphonates exert their activity is only beginning to be understood. We have studied the effects of bisphosphonate treatment on the growth of prostate cancer cell lines in vitro. Treatment of PC3, DU145, and LNCaP cells with pamidronate or zoledronate significantly reduced the growth of all three cell lines. Using flow cytometry, pamidronate treatment (100 microM) was shown to induce significant amounts of cell death in all three cell lines studied. In contrast, treatment with zoledronate (100 microM) did not induce cell death, instead exerting dramatic effects on cell proliferation, as evidenced by a major increase in cells present in the G0-G1 and S phase. Although both drugs reduced prostate cancer cell growth in the presence of serum, zoledronate was more potent under these conditions, disrupting growth at doses as low as 25 microM in the presence of 5% fetal bovine serum. These results raise the intriguing possibility that the observed clinical utility of bisphosphonates in managing skeletal metastases may in part derive from direct inhibition of prostate cancer cell growth in the bone microenvironment.

Guías para el diagnóstico y tratamiento de la enfermedad ósea de paget / Guidelines for the diagnosis and therapy of Paget's disease of the bone

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High gene flow levels lead to gamete wastage in a desert spider system.

Field censuses, breeding experiments, and a quantitative model are used to obtain insight into the extent and consequences of genetic mixing between locally adapted populations of a desert spider. Typically, 9% of the matings of desert riparian spiders (non-aggressive phenotype) in native habitat involve an arid-land partner (aggressive phenotype). Mating was found to be random with respect to behavioral phenotype, but linearly related to both the rate of immigration and survival of immigrants from surrounding arid habitats in the riparian area. Genetic mixing between riparian and arid-land spiders produces offspring that exhibit lower rates of survival in riparian habitat. Two extreme behavioral phenotypes were also observed in the field studies: approximately 5% of the female spiders attacked all males they encountered while another 22% ran from all potential mates. Punnett square analyses of the potential genotypes produced by introgression between arid- and riparian-adapted spiders indicate that these extreme phenotypes appear in F2 generation hybrids and backcrosses. Because there is a costly wastage of gametes in the case of mixed phenotype mating, model results indicate that within three generations of the cessation of gene flow, the riparian population would be free of mixed genotypes and moving towards genetic differentiation.