Prebiotic oligosaccharides in early life alter gut microbiome development in male mice while supporting influenza vaccination responses.

Beneficial modulation of the gut microbiota is an attractive therapeutic approach to improve the efficacy of vaccine-induced immunity. In this study, mice were supplemented with the prebiotic milk oligosaccharide 2'-fucosyllactose (2'FL) as well as a complex mixture of immune modulatory prebiotic short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (scGOS/lcFOS) from different stages in early life. Adult mice were vaccinated with trivalent influenza vaccine (TIV) and both development of the gut microbiota and antibody-mediated vaccine responses were followed over time. Within the control group, female mice demonstrated a larger antibody response to TIV vaccination than male mice, which was accompanied by enhanced cytokine production by splenocytes and a higher percentage of plasma cells in skin draining lymph nodes. In addition, the prebiotic diet improved vaccine-specific antibody responses in male mice. Introduction of prebiotics into the diet modulated the gut microbiota composition and at the genus level several bacterial groups showed a significant interaction effect which potentially contributed to the immunological effects observed. This study provides insight in the effect of scGOS/lcFOS/2'FL in influenza vaccination antibody production.

Performance of BRCA1/2 mutation prediction models in male breast cancer patients.

To establish whether existing mutation prediction models can identify which male breast cancer (MBC) patients should be offered BRCA1 and BRCA2 diagnostic DNA screening, we compared the performance of BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm), BRCAPRO (BRCA probability) and the Myriad prevalence table ("Myriad"). These models were evaluated using the family data of 307 Dutch MBC probands tested for BRCA1/2, 58 (19%) of whom were carriers. We compared the numbers of observed vs predicted carriers and assessed the Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) for each model. BOADICEA predicted the total number of BRCA1/2 mutation carriers quite accurately (observed/predicted ratio: 0.94). When a cut-off of 10% and 20% prior probability was used, BRCAPRO showed a non-significant better performance (observed/predicted ratio BOADICEA: 0.81, 95% confidence interval [CI]: [0.60-1.09] and 0.79, 95% CI: [0.57-1.09], vs. BRCAPRO: 1.02, 95% CI: [0.75-1.38] and 0.94, 95% CI: [0.68-1.31], respectively). Myriad underestimated the number of carriers in up to 69% of the cases. BRCAPRO showed a non-significant, higher AUC than BOADICEA (0.798 vs 0.776). Myriad showed a significantly lower AUC (0.671). BRCAPRO and BOADICEA can efficiently identify MBC patients as BRCA1/2 mutation carriers. Besides their general applicability, these tools will be of particular value in countries with limited healthcare resources.

Increases in duodenal glutamic acid supply linearly increase small intestinal starch digestion but not nitrogen balance in cattle.

Small intestinal starch digestion (SISD) in cattle is often limited; however, greater postruminal flow of high-quality protein (e.g., casein) can increase SISD, and Glu can mimic responses to casein for SISD. We evaluated effects of increasing Glu flows to the duodenum on SISD and N retention in cattle. Cattle received (DM basis) continuous duodenal infusion of raw cornstarch (1.5 ± 0.08 kg/d) and 0, 30.9 ± 0.6, 62.4 ± 1.2, or 120.4 ± 3.4 g/d Glu or 387.9 ± 17.5 g/d casein. As expected, the positive control (i.e., casein) increased ( = 0.05) SISD. Interestingly, SISD linearly increased ( = 0.02) with increasing amounts of Glu. Starch flow to the ileum linearly decreased ( = 0.04) in response to greater postruminal Glu and tended to decrease ( = 0.07) with duodenal casein infusion. Ileal flow of ethanol-soluble starch was not affected by duodenal Glu ( = 0.16) or casein ( = 0.42). There was a tendency ( = 0.08) for a quadratic response to Glu for ileal glucose flow with greater flows for intermediate levels of Glu, but casein had no effect ( = 0.81) on glucose flows to the ileum. Greater postruminal supplies of Glu (linear, = 0.05) and casein ( = 0.02) decreased fecal starch flow. Postruminal starch digestion was increased by both casein ( = 0.03) and Glu (linear, = 0.05). Nitrogen intake from feed was not different among treatments ( ≥ 0.23). By design, infusate N increased from 0 to 13 ± 1.5 g/d with greater amounts of Glu, and casein provided 61 ± 1.3 g N/d. Urinary N excretion was not affected ( ≥ 0.30) by postruminal Glu flow, but urine N was increased by casein ( < 0.01). Glutamic acid did not affect N retention ( ≥ 0.34), but casein increased N retention ( < 0.01). However, N retained as a percent of N intake (26.7 ± 1.7%) was not different when cattle were provided Glu ( ≥ 0.16) or casein ( = 0.38).

Peripheral telomere length and hippocampal volume in adolescents with major depressive disorder.

Several studies have reported that adults with major depressive disorder have shorter telomere length and reduced hippocampal volumes. Moreover, studies of adult populations without major depressive disorder suggest a relationship between peripheral telomere length and hippocampal volume. However, the relationship of these findings in adolescents with major depressive disorder has yet to be explored. We examined whether adolescent major depressive disorder is associated with altered peripheral telomere length and hippocampal volume, and whether these measures relate to one another. In 54 unmedicated adolescents (13-18 years) with major depressive disorder and 63 well-matched healthy controls, telomere length was assessed from saliva using quantitative polymerase chain reaction methods, and bilateral hippocampal volumes were measured with magnetic resonance imaging. After adjusting for age and sex (and total brain volume in the hippocampal analysis), adolescents with major depressive disorder exhibited significantly shorter telomere length and significantly smaller right, but not left hippocampal volume. When corrected for age, sex, diagnostic group and total brain volume, telomere length was not significantly associated with left or right hippocampal volume, suggesting that these cellular and neural processes may be mechanistically distinct during adolescence. Our findings suggest that shortening of telomere length and reduction of hippocampal volume are already present in early-onset major depressive disorder and thus unlikely to be only a result of accumulated years of exposure to major depressive disorder.

In- and outdoor reproduction of first generation common sole Solea solea under a natural photothermal regime: Temporal progression of sexual maturation assessed by monitoring plasma steroids and gonadotropin mRNA expression.

Reproduction of many temperate fishes is seasonal and maturation and spawning of gametes are under photothermal control. Reproductive success of first generation (G1) common sole Solea solea in captivity has been low. In this study, the sexual maturation status has been assessed during the prespawning months in G1 sole that were housed (a) outdoor under the natural photoperiod and temperature, or (b) indoor under artificial photothermal induction. Maturation was assessed in male and female G1 broodstock in November as controls, after which the remaining population was divided over two outdoor flow-through tanks placed in a pond and two indoor recirculating aquaculture system (RAS) tanks. Subsequently, maturation status (gonadosomatic index GSI and plasma levels of testosterone T and 17ß-estradiol E2) was assessed in one tank for each condition in January, February and during spawning in early April, while fish in the other tank were not disturbed in achieving reproductive success. Quantitative real-time PCR was performed to determine species-specific gonadotropin mRNA expression in females. Successful G1 spawning and egg fertilisation occurred in all experimental tanks. Gonadal development was similar under both conditions. Higher E2 and T levels were found in indoor housed females. Gonadotropin expression revealed similar profiles between outdoor and indoor housed females. G1 sole could be reproduced in the outdoor tanks under the natural photoperiod and in the indoor tanks under artificial simulation of this regime that includes a potentially crucial chilling period of 2-3 months at 5-7 °C.

Staphylococcal-derived superantigen enhances peanut induced Th2 responses in the skin.

BACKGROUND: The allergen-induced activation and expansion of IL-4 producing T helper type 2 (Th2) cells is a key event in the initiation and progression of allergic disease. Intriguingly, concomitant early childhood staphylococcal skin infections are being increasingly implicated in the allergen-induced switch of primary T cell responses towards the Th2 phenotype. OBJECTIVE: We sought to identify whether or not staphylococcal-derived superantigen can influence the primary T cell response in the skin to food allergens with a view to determining whether such exposures create the immune pathology that predisposes to the development of food allergy. METHODS: Using a novel Th2 reporter model, we determined the ability of the staphylococcal superantigen (SEB) to influence priming in the skin of IL-4 expressing Th2 cells by peanut extract (PE). Factors including the effect of SEB on the magnitude of the Th2 response in the skin draining lymph nodes, T cell receptor V region usage and the influence of endotoxin were evaluated. RESULTS: Primary exposure to PE and SEB lead to significantly enhanced PE specific Th2 responses when the mice were subsequently exposed to PE alone. The enhancement of the Th2 response was dependent on the Vß-binding properties of the SEB, but was not affected by endotoxin-mediated TLR-4 effects or strain differences in the mice. CONCLUSIONS AND CLINICAL RELEVANCE: These results identify that in the skin environment, the presence of SEB can significantly increase the numbers of allergen-induced Th2 cells which develop in response to subsequent allergen exposure. These data highlight the process by which individuals may become pathologically sensitized to food allergens in early life.

Perinatal complications increase the risk of postpartum depression. The Generation R Study.

OBJECTIVE: To examine whether specific pregnancy and delivery complications are risk factors for postpartum depression. DESIGN: A prospective longitudinal study. SETTING: Rotterdam, the Netherlands. POPULATION: A cohort of 4941 pregnant women who enrolled in the Generation R Study. METHODS: Information on perinatal complications was obtained from the midwife and hospital registries or by questionnaire. Logistic regression analyses were used to calculate the risk of postpartum depression for the separate perinatal complications. MAIN OUTCOME MEASURES: Postpartum psychiatric symptoms were assessed 2 months after delivery using the Edinburgh postnatal depression scale. RESULTS: Several perinatal complications were significantly associated with postpartum depression, namely: pre-eclampsia (adjusted OR, aOR 2.58, 95% CI 1.30-5.14), hospitalization during pregnancy (aOR 2.25, 95% CI 1.19-4.26), emergency caesarean section (aOR 1.53, 95% CI 1.02-2.31), suspicion of fetal distress (aOR 1.56, 95% CI 1.08-2.27), a medically indicated delivery provided by an obstetrician (aOR 2.43, 95% CI 1.56-3.78), and hospital admission of the baby (aOR 1.45, 95% CI 1.10-1.92). Unplanned pregnancy, thrombosis, meconium-stained amniotic fluid, and Apgar score were not associated with postpartum depression after adjustment for confounding factors, such as pre-existing psychopathological symptoms and sociodemographic characteristics. The risk of postpartum depression increased with the number of perinatal complications women experienced (P < 0.001). CONCLUSIONS: We showed that several pregnancy and delivery complications present a risk for women's mental health in the postpartum period. Obstetricians, midwives, general practitioners, and staff at baby well clinics should be aware that women who experienced perinatal complications-especially those with a number of perinatal complications-are at risk for developing postpartum depression.

Heart rate variability (HRV) in adolescent females with anxiety disorders and major depressive disorder.

AIM: The aim of this study was to investigate heart rate variability (HRV) in a clinical sample of female adolescents with anxiety disorders (AD) and/or major depressive disorder (MDD) compared with healthy controls and to assess the effect of selective serotonin reuptake inhibitors (SSRI) on HRV. METHODS: Heart rate variability was measured in adolescent female psychiatric patients with AD and/or MDD (n = 69), mean age 16.8 years (range: 14.5-18.4), from 13 out-patient clinics and in healthy controls (n = 65), mean age 16.5 years (range: 15.9-17.7). HRV was registered in the sitting position during 4 min with no interventions. RESULTS: Logarithmically transformed high frequency HRV (HF), low frequency HRV (LF) and standard deviation of inter beat intervals (SDNN) were lower in the clinical sample compared with the controls (Cohen's d for HF = 0.57, LF = 0.55, SDNN = 0.60). This was not explained by body mass index, blood pressure or physical activity. Medication with SSRI explained 15.5% of the total variance of HF, 3.0% of LF and 6.5% of SDNN. CONCLUSIONS: Adolescent female psychiatric patients with AD and/or MDD show reduced HRV compared with healthy controls. Medication with SSRI explained a part of this difference.

Unique skin changes in a case of Albright hereditary osteodystrophy caused by a rare GNAS1 mutation.

Albright hereditary osteodystrophy (AHO) is a syndrome of short stature, obesity, brachydactyly and subcutaneous calcifications with pseudohypoparathyroidism (PHP; leading to hypocalcaemia, hyperphosphataemia and elevated levels of parathyroid hormone, PTH). It was first described over 60 years ago. Since then, much has been learned about the aetiology of AHO which has been shown to be caused by heterozygous loss-of-function mutations within the GNAS1 gene. GNAS1 is subject to imprinting leading to phenotypic heterogeneity within kindreds with one mutation. Patients with AHO often present with symptoms of hypocalcaemia and/or with subcutaneous calcifications. The latter is thought to be the typical skin abnormality in AHO. We describe a family with AHO and hormone resistance (PHP type Ia) resulting from a rare mutation in GNAS1. The proband presented with small subcutaneous calcifications in the helix of the right ear and concentrated in a sharply demarcated zone of subcutaneous and dermal hypoplasia. This abnormality has so far not been described in patients with AHO. We speculate on the mechanism of dermal hypoplasia and resistance to PTH and suggest that subcutanous or dermal hypoplasia might be another feature which can be present in patients with AHO.

Using undergraduate nursing students as mediators in a knowledge transfer programme for care for patients with advanced cancer.

Nursing today faces numerous challenges. Societal changes lead to reorganization of health care, changing workloads with sicker patients in hospital and home care, and limited economic resources. The increasing and changing nature of knowledge needed for expert care provision challenges nurses to continually update their competencies. These are issues demanding proactive and dynamic changes in the way nurses conceive their mandates and practice. The aim of the action-research project presented here was to foster improved quality of care for patients with advanced cancer through collaborative endeavours integrating cancer nursing clinical practice, research and education in a knowledge exchange programme. The programme was based on input about caregiving needs from multi-professional staff caring for patients with advanced cancer in a variety of healthcare settings. Undergraduate baccalaureate nursing students were then engaged in literature studies to help address these needs. Results of the studies were communicated back to the involved clinicians in a variety of ways. In this paper, we discuss what we have experienced as opportunities and obstacles in conducting the project, based on our reflections and external evaluations. This is linked to a broader discussion of ways of integrating cancer nursing research, education and practice.

Analysis of verbal communication during teaching in the operating room and the potentials for surgical training.

BACKGROUND: Verbal communication in the operating room during surgical procedures affects team performance, reflects individual skills, and is related to the complexity of the operation process. During the procedural training of surgeons (residents), feedback and guidance is given through verbal communication. A classification method based on structural analysis of the contents was developed to analyze verbal communication. This study aimed to evaluate whether a classification method for the contents of verbal communication in the operating room could provide insight into the teaching processes. METHODS: Eight laparoscopic cholecystectomies were videotaped. Two entire cholecystectomies and the dissection phase of six additional procedures were analyzed by categorization of the communication in terms of type (4 categories: commanding, explaining, questioning, and miscellaneous) and content (9 categories: operation method, location, direction, instrument handling, visualization, anatomy and pathology, general, private, undefinable). The operation was divided into six phases: start, dissection, clipping, separating, control, closing. RESULTS: Classification of the communication during two entire procedures showed that each phase of the operation was dominated by different kinds of communication. A high percentage of explaining anatomy and pathology was found throughout the whole procedure except for the control and closing phases. In the dissection phases, 60% of verbal communication concerned explaining. These explaining communication events were divided as follows: 27% operation method, 19% anatomy and pathology, 25% location (positioning of the instrument-tissue interaction), 15% direction (direction of tissue manipulation), 11% instrument handling, and 3% other nonclassified instructions. CONCLUSION: The proposed classification method is feasible for analyzing verbal communication during surgical procedures. Communication content objectively reflects the interaction between surgeon and resident. This information can potentially be used to specify training needs, and may contribute to the evaluation of different training methods.

New Alzheimer's disease locus on chromosome 8.

BACKGROUND: Family history is one of the most consistent risk factors for dementia. Therefore, analysis of families with a distinct inheritance pattern of disease can be a powerful approach for the identification of previously unknown disease genes. OBJECTIVE: To map susceptibility regions for Alzheimer's disease. METHODS: A complete genome scan with 369 microsatellite markers was carried out in 12 extended families collected in Sweden. Age at disease onset ranged from 53 to 78 years, but in 10 of the families there was at least one member with age at onset of < or =65 years. Mutations in known early-onset Alzheimer's disease susceptibility genes have been excluded. All people were genotyped for APOE, but no clear linkage with the epsilon4 allele was observed. RESULTS: Although no common disease locus could be found in all families, in two families an extended haplotype was identified on chromosome 8q shared by all affected members. In one of the families, a non-parametric multimarker logarithm of the odds (LOD) score of 4.2 (p = 0.004) was obtained and analysis based on a dominant model showed a parametric LOD score of 2.4 for this region. All six affected members of this family shared a haplotype of 10 markers spanning about 40 cM. Three affected members in another family also shared a haplotype in the same region. CONCLUSION: On the basis of our data, we propose the existence of a dominantly acting Alzheimer's disease susceptibility locus on chromosome 8.

Transforming growth factor-beta1 incorporation in an alpha-tricalcium phosphate/dicalcium phosphate dihydrate/tetracalcium phosphate monoxide cement: release characteristics and physicochemical properties.

The osteoconductive properties of calcium phosphate cements (CPCs) may be improved by the addition of growth factors, such as recombinant human transforming growth factor-beta1 (rhTGF-beta1). Previously we have shown that rhTGF-beta1 was released from cement enriched with rhTGF-beta1 and subsequently stimulated the differentiation of pre-osteoblastic cells from adult rat long bones. It is unknown whether the addition of rhTGF-beta1 changes the material properties of this alpha-tricalcium-phosphate (alpha-TCP)/tetracalcium-phosphate-monoxide (TeCP)/dicalcium-phosphate-dihydrate (DCPD) cement, and what the characteristics of the release of rhTGF-beta1 from this CPC are. Therefore, in the present study we determined the release of rhTGF-beta1 from cement pellets in vitro. The possible intervening effects of the CPC modification for intermixing rhTGF-beta1 on physicochemical properties were studied by assessing the compressive strength and setting time, as well as crystallinity, calcium to phosphorus ratio, porosity and microscopic structure. Most of the previously incorporated rhTGF-beta1 in the cement pellets was released within the first 48 h. For all concentrations of rhTGF-beta1 intermixed (100 ng-2.5 mg/g CPC), approximately 0.5% of the amount of rhTGF-beta1 incorporated initially was released in the first 2 h, increasing to 1.0% after 48 h. The release of rhTGF-beta1 continued hereafter at a rate of about 0.1% up to 1 week, after which no additional release was found. The initial setting time, nor the final setting time was changed in control cement without rhTGF-beta1 (standard CPC) or in cement modified for rhTGF-beta1 (modified CPC) at 20 degrees C and 37 degrees C. Setting times were more than six times decreased at 37 degrees C compared to 20 degrees C. The compressive strength was initially low for both standard CPC and modified CPC, after which it increased between 24 h and 8 weeks. The compressive strength for the modified CPC was significantly higher compared with standard at 1, 2, and 8 weeks after mixing. X-ray diffraction revealed that both standard and modified CPC changed similarly from the original components into crystalline apatite. The calcium to phosphorus ratio as determined by an electron microprobe did not differ at all time points measured for standard CPC and modified CPC. In both standard CPC and modified CPC the separated particles became connected by crystals, forming a structure in which the particles could hardly be recognised in a densifying matrix with some small pores. The present study shows that the calcium phosphate cement is not severely changed by modification for the addition of rhTGF-beta1. The addition of rhTGF-beta1 in CPC enhances the biologic response as shown in our previous study and did not interfere with the aimed physical and chemical properties as shown in this study. We conclude that the addition of rhTGF-beta1 enlarges the potential of the CPC in bone replacement therapy.

Transforming growth factor-beta1 incorporation in a calcium phosphate bone cement: material properties and release characteristics.

The bone regenerative properties of calcium phosphate cements (CPCs) may be improved by the addition of growth factors, such as recombinant human transforming growth factor-beta1 (rhTGF-beta1). Previously, we showed that rhTGF-beta1 in CPC stimulated the differentiation of preosteoblastic cells from adult rat long bones. The intermixing of rhTGF-beta1 in CPC, which was subsequently applied to rat calvarial defects, enhanced bone growth around the cement and increased the degradation of the cement. However, it is unknown whether the addition of rhTGF-beta1 changes the material properties of CPC and what the characteristics of the release of rhTGF-beta1 from CPC are. Therefore, we determined in this study the release of rhTGF-beta1, in vitro, from the cement pellets as implanted in the rat calvariae. The possible intervening effects of rhTGF-beta1 intermixing on the clinical compliance of CPC were studied through an assessment of its compressive strength and setting time, as well as its crystallinity, calcium-to-phosphorus ratio, porosity, and microscopic structure. We prepared CPC by mixing calcium phosphate powder (58% alpha-tricalcium phosphate, 25% anhydrous dicalcium phosphate, 8.5% calcium carbonate, and 8.5% hydroxyapatite) with a liquid (3 g/mL). The liquid for standard CPC consisted of water with 4% disodium hydrogen phosphate, whereas the liquid for modified CPC was mixed with an equal amount of 4 mM hydrochloride with 0.2% bovine serum albumin. The hydrochloride liquid contained rhTGF-beta1 in different concentrations for the release experiments. Most of the rhTGF-beta1 incorporated in the cement pellets was released within the first 48 h. For all concentrations of intermixed rhTGF-beta1 (100 ng to 2.5 mg/g of CPC), approximately 0.5% was released in the first 4 h, increasing to 1.0% after 48 h. Further release was only about 0.1% from 2 days to 8 weeks. CPC modification slightly increased the initial setting time at 20 degrees C from 2.6 to 5 min but had no effect on the final setting time of CPC at 20 degrees C or the initial and final setting times at 37 degrees C. The compressive strength was increased from 18 MPa in the standard CPC to 28 MPa in the modified CPC only 4 h after mixing. The compressive strength diminished in the modified CPC between 24 h and 8 weeks from 55 to 25 MPa. No other significant change was found with the CPC modification for rhTGF-beta1. X-ray diffraction revealed that standard and modified CPCs changed similarly from the original components, alpha-tricalcium phosphate and anhydrous dicalcium phosphate, into an apatite cement. The calcium-to-phosphorus ratio, as determined with an electron microprobe, did not differ for standard CPC and modified CPC. Standard and modified CPCs became dense and homogeneous structures after 24 h, but the modified CPC contained more crystal plaques than the standard CPC, as observed with scanning electron microscopy (SEM). SEM and back- scattered electron images revealed that after 8 weeks the cements showed equally and uniformly dense structures with microscopic pores (<1 microm). Both CPCs showed fewer crystal plaques at 8 weeks than at 24 h. This study shows that CPC is not severely changed by its modification for rhTGF-beta1. The prolonged setting time of modified cement may affect the clinical handling but is still within acceptable limits. The compressive strength for both standard and modified cements was within the range of thin trabecular bone; therefore, both CPCs can withstand equal mechanical loading. The faster diminishing compressive strength of modified cement from 24 h to 8 weeks likely results in early breakdown and so might be favorable for bone regeneration. Together with the beneficial effects on bone regeneration from the addition of rhTGF-beta1 to CPC, as shown in our previous studies, we conclude that the envisaged applications for CPC in bone defects are upgraded by the intermixing of rhTGF-beta1. Therefore, the combination of CPC and rhTGF-beta1 forms a promising synthetic bone graft.

Transforming growth factor-beta1 incorporated in calcium phosphate cement stimulates osteotransductivity in rat calvarial bone defects.

Bone regeneration of the alveolar crest around dental implants is an important factor in the success of implant use. Calcium phosphate cement can be used as a bone substitute and applied clinically as a paste to fill micro- and macroscopic bone defects. We have shown earlier that the intermixing of the recombinant human transforming growth factor-beta1 (rhTGF-beta1) in hardening calcium phosphate cement stimulated osteoblastic differentiation of rat primary bone cells in vitro. The aim of the present study was to examine whether the similar enrichment with rhTGF-beta1 affects the replacement of calcium phosphate cement by bone (osteotransduction) in calvarial critical size defects (csd) of adult rats. Two bone defects of 5 mm diameter were created bilaterally in each skull of 10 adult male rats. Both defects were filled with 53 mg of calcium phosphate cement without rhTGF-beta1 (control) at one side, and with 10 or 20 ng rhTGF-beta1 at the other side. After 8 weeks, defects with surrounding skull were analysed histologically and histomorphometrically. The addition of rhTGF-beta1 in the cement increased the amount of bone in rat skull defects. This finding coincidences with our in vitro observations, that intermixing of rhTGF-beta1 in calcium phosphate cement stimulates bone cell differentiation. Addition of rhTGF-beta1 stimulated bone formation as indicated by an increased bone volume of 50% and an increased bone/cement contact of 65%, in comparison to control defects with cement without rhTGF-beta1. In addition, rhTGF-beta1 reduced the remaining volume of cement, by 11% at 10 ng rhTGF-beta1, and by 20% at 20 ng rhTGF-beta1 in the cement. Defect closure was not affected. We conclude that the intermixing of rhTGF-beta1 in a fast-setting calcium phosphate cement stimulates bone growth and the osteotransduction of the cement. For bone regeneration procedures around endosseous implants, calcium phosphate cement with rhTGF-beta1 might be an appropriate combination for early osseointegration and implant use.

Is good 'quality of life' possible at the end of life? An explorative study of the experiences of a group of cancer patients in two different care cultures.

The purpose of this paper was to explore how a group of gravely ill patients, cared for in different care cultures, assessed their quality of life during their last month of life. The study material comprised quality of life assessments from 47 cancer patients, completed during their last month of life. Two quality of life questionnaires, the EORTC QLQ-C30 and a psychosocial well-being questionnaire, were used. The data were treated in accordance with instructions for the respective questionnaires, and the results are presented primarily as means, mostly at the group level. Assessments from patients in two different care cultures, care-orientated and cure-orientated, were compared. The results show that despite having an assessed lower quality of life in many dimensions than people in general, several patients experienced happiness and satisfaction during their last month of life. 'Cognitive functioning' and 'emotional functioning' were the dimensions that differed least from those of the general population, and 'physical functioning', 'role functioning' and 'global health status/quality of life' differed the most. 'Fatigue' showed the highest mean for the symptom scales/items. There was a tendency for those cared for in the cure-orientated care culture to report more symptoms than those in the care-orientated care culture. An exception to this was 'pain', which was reported more often by those in the care-orientated care culture. The implications of the results are discussed from different angles. The significance of knowledge concerning how patients experience their quality of life is also discussed with respect to the care and the planning of care for dying patients.

Current status of voice restoration following total laryngectomy.

Total laryngectomy is the surgical procedure traditionally used to treat patients with advanced-stage cancer of the larynx. The impairments resulting from removal of such a small organ are, indeed, profound. They include loss of voice and speech; altered respiration, necessitating a permanent breathing opening in the neck; and diminished sense of smell and taste. When one considers these factors, successful treatment of laryngeal cancer cannot be measured by survival rate alone. Rapid, effective restoration of voice and speech is one of the primary focuses of rehabilitation and is pivotal to the prevention of the potential psychosocial and economic consequences of total laryngectomy. This article focuses on the methods of voice restoration currently being employed to reestablish the ability to speak.

Frontal sinus stents.

OBJECTIVES: The formation of scar tissue, synechiae, or osteogenesis in the narrow frontal outflow tract after instrumentation of the frontal sinus has led to attempts to enlarge the frontal duct or stenting. STUDY DESIGN: Prospective pilot study. RESULTS: Sixty-four Freeman frontal sinus stents were used to maintain patency in 46 patients. Stents were inserted using an endoscopic technique in 26 sinuses containing polyps, 20 with pansinusitis, and 18 cavities with stenosis of the frontal duct. External incisions with frontal sinusotomy were required to remove the stenosis and insert the stent in nine sinuses. Polypoid degeneration, granulation, purulent drainage, and lateralization of the middle turbinate were encountered infrequently. Frontal obliteration was subsequently required in six sinuses. CONCLUSION: The Freeman frontal sinus stent prevented blockage of the outflow tract in patients who had removal of disease in the sinus or duct or treatment of frontal stenosis.

Transforming growth factor-beta1 incorporated during setting in calcium phosphate cement stimulates bone cell differentiation in vitro.

Growth stimulation of periimplant tissues by growth factors like transforming growth factor-beta1 (TGF-beta1) may increase the indication for and success of implant use. Calcium phosphate as a material for implants or for coating of implants is known for its good biologic interaction with bone. Therefore, calcium phosphate implants combined with TGF-beta1 might improve osseointegration. In this study we hypothesise that the addition of recombinant human TGF-beta1 (rhTGF-beta1) to calcium phosphate cement (CPC) affects the differentiation of bone cells growing on the cement layer. rhTGF-beta1 incorporated during setting in a CPC layer at 20 ng rhTGF-beta1/60 mg cement was found to be gradually released into tissue culturing medium leading to a 20% release after 24 h. Two cell populations were obtained from collagenase-treated fragments of adult rat long bones: preosteoblastic cells, which were released by the collagenase treatment, and osteoblastic cells, which grew from the collagenase-stripped bone fragments. Both cell populations were tested for their osteoblastic characteristic phenotype by measuring their alkaline phosphatase (ALP) activity after vitamin D treatment and cyclic AMP after parathyroid hormone stimulation. After preculture the cells were plated on a layer of CPC containing 0 (control), 10, or 20 ng rhTGF-beta1/60 mg CPC. Bone cell differentiation was analyzed after 10 days by measuring the ALP activity, as well as the protein content of the cell layer. Incorporation of rhTGF-beta1 in the CPC did not change the ALP activity in osteoblastic cells, but a significant (analyzed by multivariate analysis of variance) increase was observed in preosteoblastic cells. Incorporation of 10 ng of rhTGF-beta1 in 60 mg of CPC increased the ALP activity in preosteoblastic cells by threefold and 20 ng rhTGF-beta1/60 mg CPC increased it by fivefold. The total protein content was not affected by rhTGF-beta1 in either of the cell populations. We conclude that rhTGF-beta1 incorporated during setting in CPC stimulates the differentiation of preosteoblastic cells in vitro. These results provide a basis for further studies on the use of this combination as an implant material in vivo.