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.

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.

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.

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.

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.

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.

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.

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.

Cortical bone ingrowth in growth hormone-loaded grooved implants with calcium phosphate coatings in goat femurs.

Dental implants are successfully used for tissue-integrated protheses, but the long-term survival in the maxilla is shorter than in the mandible [Cune MS, Thesis, University of Utrecht, 1993; Jaffin RA, Berman CL. J Periodontol 1991;62:2-4]. However, by adding growth hormone at implantation, increased bone apposition may be expected, since it is known that growth hormone has a stimulating effect on the differentiation and proliferation of osteoblastic cells [Ernst M, Froesch ER. Biochem Biophys Res Commun 1988;151:142-47; Scheven BAA et al. Growth Regul 1991;1:160-67; Stracke H et al. Acta Endocrinol 1984;107:16-24]. We studied bone ingrowth and bone contact of grooved implants impregnated with growth hormone in the cortex of femurs of female goats. We compared the effect of growth hormone on grooved implants with or without calcium phosphate coatings at the bottom of the grooves. The coatings used were hydroxyapatite, fluorapatite and heat-treated hydroxyapatite. The implants had both small and large grooves. The implants were positioned in the cortex of one femur and were treated with recombinant human growth hormone, while the implants on the opposite femur served as controls. After 6 weeks, the implants and surrounding tissues were dissected and evaluated histomorphologically and morphometrically by light microscopy. The bone ingrowth and the bone contact in the grooves were quantified by digital image analysis. Calcium phosphate coating at the bottom of the grooves resulted in a significant increase of bone ingrowth and bone contact. Small grooves had significantly more bone ingrowth and bone contact than the larger grooves. However, all implants impregnated with growth hormone showed inhibition of bone contact and bone ingrowth. We conclude that recombinant human growth hormone inhibits bone formation in the grooves coated with calcium phosphate. Without the addition of growth hormone, the calcium phosphate coatings improved bone ingrowth and bone contact in the grooves. Further studies are required to determine whether growth hormone could also possibly act as a bone growth promoting factor in these implants.

Elimination of alkaline phosphatases from circulation by the galactose receptor. Different isoforms are cleared at various rates.

Three isoforms of human alkaline phosphatase (liver, bone and placental ALP) were purified and their elimination studied after intravenous injection in rats. The rates of elimination were significantly inhibited by prior injection of asialofetuin, indicating that the uptake was mediated by the galactose receptor in liver. Their relative clearance rates differed, being rapid for the bone ALP, significantly slower for the liver isoform and very slow for the placental ALP. The bone ALP showed a rapid initial clearance, apparently related to its large glycan heterogeneity and to the presence of molecules with a low sialic acid content. When isolated from serum the liver and bone ALP isoforms showed clearance rates differing slightly from those of the organ derived forms. We conclude that differences in carbohydrate structure and amount of sialic acid of the three isoforms result in various clearance rates. These differences will also affect their serum concentrations as well as the composition and heterogeneity of the individual isoforms in serum.

beta-Aminoisobutyric acid as a marker of thymine catabolism in malignancy.

Urine from untreated patients with various tumours and controls has been examined for the excretion of beta-aminoisobutyric acid and uric acid. The patients were classified into four groups: I, beta-aminoisobutyric acid and uric acid both normal; II, beta-aminoisobutyric acid normal, uric acid elevated; III, beta-aminoisobutyric acid elevated, uric acid normal; IV, beta-aminoisobutyric acid and uric acid both elevated. Uric acid was used as an indicator for tissue-breakdown. Pseudouridine being a specific parameter for t-RNA degradation was estimated for comparison. Increased urinary concentrations of beta-aminoisobutyric acid were frequently found in tumour patients, especially in patients with leukaemia and non-Hodgkin lymphoma. Tissue breakdown being the cause of the beta-aminoisobutyric aciduria could only be considered in part of the patients. Moreover, strongly elevated ratios of beta-aminoisobutyric acid to uric acid were found. Urinary patterns of pyrimidines and purines were determined in order to exclude other abnormalities. The results are discussed in relation to thymine metabolism and renal function.

Urinary purines and pyrimidines in patients with hyperammonemia of various origins.

Excretion patterns of pyrimidines and purines in patients with various types of hyperammonemia have been investigated by 2-dimensional thin-layer chromatography and high pressure liquid chromatography (HPLC). For the quantitative analysis of pseudouridine, uracil and uridine a new procedure has been developed, consisting of pre-fractionation with Dowex 1 X 8, followed by dual column HPLC on a strong anion-exchanger and a reverse phase column. Thymine has also been analyzed in the pre-fractionated urine by a new HPLC method using the reverse phase column in combination with a strong cation-exchange column. Quantitative data for urinary pyrimidines and uric acid in hyperammonemia are given. In patients with a defect in one of the urea cycle enzymes, the level of pyrimidine excretion was found to depend on plasma ammonia concentrations. In other hyperammonemic patients, an increased excretion of orotic acid, uracil and uridine has only been found in one of the two patients with lysinuric protein intolerance, all other patients showing normal excretion patterns. Elevated uric acid excretions have been found frequently in our patients with hyperammonemia, but they did not always coincide with high plasma ammonia levels. A possible explanation for the difference in the excretion levels of the various pyrimidines is discussed.

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.

Functional outcome after surgery for prevention of pharyngospasms in tracheoesophageal speakers. Part I: Speech characteristics.

The speech characteristics of 29 patients with primary tracheoesophageal puncture who received either a pharyngeal constrictor myotomy, a unilateral pharyngeal plexus neurectomy, or a unilateral pharyngeal plexus neurectomy with drainage myotomy limited to the cricopharyngeus were studied. All patients used a Blom-Singer low-pressure voice prosthesis. Audio recordings of each patient speaking with both the Blom-Singer tracheostoma valve and manual occlusion of the tracheostoma were recorded at 3 weeks, 6 months, and 12 months after surgery. The three surgical variations were equally effective at preventing pharyngospasms; only 1 patient (10%) in each group had some loss of fluency during the 12-month study period. Neurectomized patients produced significantly higher fundamental frequencies during reading than did patients in the other groups. Residual resting tone in the neurectomized pharyngoesophageal segment may contribute to more favorable speaking frequencies in this group.