Disruptive viability selection on a black plumage trait associated with dominance.

Traits used in communication, such as colour signals, are expected to have positive consequences for reproductive success, but their associations with survival are little understood. Previous studies have mainly investigated linear relationships between signals and survival, but both hump-shaped and U-shaped relationships can also be predicted, depending on the main costs involved in trait expression. Furthermore, few studies have taken the plasticity of signals into account in viability selection analyses. The relationship between signal expression and survival is of particular interest in melanin-based traits, because their main costs are still debated. Here, we first determined the main factors explaining variability in a melanin-based trait linked to dominance: the bib size of a colonial bird, the sociable weaver Philetairus socius. We then used these analyses to obtain a measure representative of the individual mean expression of bib size. Finally, we used capture-recapture models to study how survival varied in relation to bib size. Variation in bib size was strongly affected by year and moderately affected by age, body condition and colony size. In addition, individuals bearing small and large bibs had higher survival than those with intermediate bibs, and this U-shaped relationship between survival and bib size appeared to be more pronounced in some years than others. These results constitute a rare example of disruptive viability selection, and point towards the potential importance of social costs incurred by the dominance signalling function of badges of status.

Homozygosity mapping of a gene for arterial tortuosity syndrome to chromosome 20q13.

BACKGROUND: Arterial tortuosity syndrome (ATS) is an uncommon connective tissue disorder of unknown aetiology. The most prominent feature is tortuosity of the large arteries, but lengthening, stenosis, and aneurysm formation are also frequent. METHODS: We performed a genomewide screen by homozygosity mapping of three consanguineous multiplex families, two from Morocco, and one from Italy, which included 11 ATS patients. The two families from Morocco may possibly have a common ancestor. RESULTS: We mapped the ATS gene to chromosome 20q13. Recombinations within an extended haplotype of 11 microsatellite markers localised the ATS gene between markers D20S836 and D20S109, an interval of 9.5 cM. CONCLUSIONS: Cloning and completing functional and structural analysis of the ATS gene may provide new insights into the molecular mechanisms of elastogenesis.

Comprehensive molecular screening of the FBN1 gene favors locus homogeneity of classical Marfan syndrome.

In order to estimate the contribution of mutations at the fibrillin-1 locus (FBN1) to classical Marfan syndrome (MFS) and to study possible phenotypic differences between patients with an FBN1 mutation vs. without, a comprehensive molecular study of the FBN1 gene in a cohort of 93 MFS patients fulfilling the clinical diagnosis of MFS according to the Ghent nosology was performed. The initial mutation screening by CSGE/SSCP allowed identification of an FBN1-mutation in 73 patients. Next, sequencing of all FBN1-exons was performed in 11 mutation-negative patients, while in nine others, DHPLC was used. This allowed identification of seven and five additional mutations, respectively. Southern blot analysis revealed an abnormal hybridization pattern in one more patient. A total of 23 out of the 85 mutations identified here are reported for the first time. Phenotypic comparison of MFS patients with cysteine-involving mutations vs. premature termination mutations revealed significant differences in ocular and skeletal involvement. The phenotype of the eight patients without proven FBN1 mutation did not differ from the others with respect to the presence of major cardiac, ocular, and skeletal manifestations or positive familial history. Most likely, a portion of FBN1-mutations remains undetected because of technical limitations. In conclusion, the involvement of the FBN1-gene could be demonstrated in at least 91% of all MFS patients (85/93), which strongly suggests that this gene is the predominant, if not the sole, locus for MFS.

Determination of ascorbic acid and isoascorbic acid by capillary zone electrophoresis: application to fruit juices and to a pharmaceutical formulation.

Capillary zone electrophoresis was applied to the determination of ascorbic and isoascorbic acid, analysing the various parameters of influence such as the separation voltage, the buffer pH and concentration, the type of separation capillary or the loading conditions. Both analytes could be adequately determined within 5 min. The proposed method uses a 20 cm x 25 microns i.d. coated column, 0.1 M phosphate buffer pH 5.0, 8 kV separation voltage and light absorption detection at 265 nm. Linear calibration curves were obtained in the 0-1 mg mi-1 range, with detection limits of 0.5 micrograms ml-1. This method proved to be very rapid, simple and practical for the qualitative and quantitative determination of ascorbic acid in lemon and orange juices, as well as in a commercially available pharmaceutical formulation.

Status of immunization and iron nutrition in New York City homeless children.

A retrospective review of the hospital records of New York City children aged 6 months through 6 years showed that 63 homeless children had a higher rate of immunization delay than an age- and sex-stratified sample of 63 domiciled children living at the same federal poverty level. In a logistic regression model, this difference persisted after controlling for sex, age, ethnicity, presence of chronic illness, and reason for referral. In a 6-month- to 2-year-old subgroup, homeless and domiciled children had equal rates of anemia, but homeless children were more likely to have elevated erythrocyte protoporphyrin (EP) levels consistent with iron deficiency. This difference, too, persisted after controlling for the same confounding factors. Elevated EP levels and immunization delay were likely to coexist in the homeless children. The higher rate of immunization delay is compatible with the occurrence of measles outbreaks in some New York City shelters. The higher rates of iron deficiency may reflect overall poor nutrition. All these findings have significant implications for the design of health-care programs for homeless children.

[Haemagnioma of the liver in newborn infant (author's transl)]. / Haemagnioom van de lever bij een prematuur

A case of a giant cavernous and capillary haemangioma of the liver in newborn infant occurred. Resection of the tumor by right hepatic lobectomy was carried out without morbidity or permanent derangement of liver function. There was regeneration of the liver.

Genetic causes of familial hypercholesterolaemia in a Malaysian population.

A total of 86 unrelated Malaysian patients with familial hypercholesterolaemia (FH) were studied for mutations in their low-density lipoprotein receptor (LDL-R) gene. Amongst them, 23 had a LDL-R gene mutation, while none having an Apolipoprotein B-3500 (Apo B-3500) mutation. Patients with the LDL-R gene defect appeared to have a higher level of low-density lipoprotein cholesterol (LDL-C), an increased incidence of xanthomas and coronary heart disease (CHD), but no relationships were found between the type of LDL-R gene mutations and their lipid levels or clinical signs of CHD. In contrast to Western data, our findings seemed to indicate a predominance of mutations in the ligand binding domain and an absence of Apo B-3500 gene mutation. The latter finding may offer a genetic basis as to why Asian patients with familial hypercholesterolaemia have lower LDL-C levels and less premature CHD than their Western counterparts.

High prevalence of a novel mutation in the exon 4 of the low-density lipoprotein receptor gene causing familial hypercholesterolemia in Belgium.

In a cohort of 70 unrelated patients living in Southern Belgium with autosomal dominantly inherited hypercholesterolemia, 11 had a hitherto undescribed mutation in exon 4. It consisted in a C-->A mutation at nucleotide 366, resulting in a stop codon at residue Cys122. This C122X mutation is expected to cause a class I receptor defect. The biochemical and clinical data collected from the patients carrying the mutation were consistent with a severe form of familial hypercholesterolemia (FH). Some differences between generations were noted. Amongst the C122X carriers, those born after 1926 had cardiovascular complications earlier than those born before 1926. This raises the possibility that changes in environmental factors during the course of the century have had an unfavorable impact on the prognosis of the disease. The mutation was found in 16% of the suspected FH patients and less frequently (less than 3% of suspected FH) in Northern Belgium. The haplotype of the chromosomes carrying the mutation was the same in all C122X families, but extensive genealogical studies failed to reveal a common ancestor. We conclude that C122X is an old and common cause of FH in Belgium. Screening for this mutation may be useful in the diagnosis of FH in Belgium.

The effect of semi-automatic external defibrillation by emergency medical technicians on survival after out-of-hospital cardiac arrest: an observational study in urban and rural areas in Belgium.

The introduction of semi-automatic external defibrillators (SAEDs) allowed emergency medical technicians (EMTs) to deliver electroshocks in cases of out-of-hospital ventricular fibrillation (VF) or ventricular tachycardia (VT), often many minutes before the arrival of the mobile intensive care unit (MICU) team. In this observational study we report on the results obtained by the EMTs from the fire departments of Gent, Aalter and Brugge. In Gent, an SAED project started in May 1991. By December 1995, the SAED's electrodes had been attached in 367 cardiac arrest patients. The first rhythm detected by the device was asystole or electromechanical dissociation (EMD) in 241 patients (66%): only 5 of these patients survived to hospital discharge (2%). In the remaining 126 VF/VT cases (34%) the survival rate was 21% (26/126). In 14 of these 26 patients the shock(s) delivered by the EMTs restored spontaneous circulation before the arrival of the MICU team, with only venous cannulation and/or intubation being performed by the MICU team. In 4 other VF patients, the shock(s) delivered by EMTs converted the VF, with the MICU team successfully taking care of VF/VT relapses or postcountershock EMD. In the remaining 8 VF/VT cases, only the MICU attempts could resuscitate the patient. The SAED project in Aalter was set up in April 1993. By December 1995, care was taken for only 21 patients. None of the 4 VF/VT patients and the 17 asystole/EMD patients survived. In Brugge, there were 240 cardiac arrest cases treated with SAED between January 1991 and December 1995. Among the 89 VF/VT cases, there were 20 survivors (22%): 8 cases survived thanks to SAED shock(s) delivered by EMTs, in 3 cases survival was due to the combination of SAED shock(s) by EMTs and extensive ALS treatment by the MICU team, and in 9 cases restoration of spontaneous circulation was only obtained after application of ALS techniques by the MICU team. This observational study seems to show a beneficial effect of the introduction of SAED in Gent and Brugge. In Aalter the number of treated cases is tool low to draw conclusions. Anyhow, the global survival rate in the three areas remains low. Therefore, more efforts are needed to strengthen the other links of the chain of survival (early access to the emergency medical services-system, early basic cardiopulmonary resuscitation and early advanced life support.

[Sentinel lymph node excision. Treatment method of the N0 neck in patients with oral and oropharyngeal carcinoma]. / Sentinel-Lymphknotenexstirpation. Behandlungsmethode des N0-Halses bei Patienten mit oralen und oropharyngealen Karzinomen.

BACKGROUND: The clinically non-metastatic neck is an unsolved problem in the treatment of oral and oropharyngeal squamous cell carcinomas. A rational procedure is looked for which is neither exaggerated nor neglects the needed safety. PATIENTS AND METHODS: 15 patients with primary squamous cell carcinomas of the oral cavity and the oropharynx, staging T1-4N0M0 were examined. After peritumoral intramucodermal injection of tc99m-labeled colloidal albumin the lymphoscintigraphy using gamma-camera imaging prior and hand-held gamma-probe during operation were used for identification of the nodes. Selective sentinel lymph node exstirpation was followed by radical tumor resection. RESULTS: In all cases (n = 41) lymph nodes could be detected, 40 of them were sentinel lymph nodes, distributed to all neck levels, in 5 cases bilateral drainage. 92.5% of sentinel lymph nodes could be actually removed. All but 1 (97.5%) were true-negative. In the positive case modified radical neck dissection harvested another affected node. CONCLUSIONS: Methodically seen, the sentinel procedure works well and might lead to reduced post-surgical morbidity in about 50% of patients with oral cancer. To date, the procedure should be confined to studies with special requirements to diagnostics and subsequent treatment.

Radioisotope-guided surgery in patients with pheochromocytoma and recurrent medullary thyroid carcinoma: a comparison of preoperative and intraoperative tumor localization with histopathologic findings.

BACKGROUND: The objective of this study was to appraise the detection of metastases of medullary thyroid carcinoma (MTC) and pheochromocytoma using radioguided surgery (RGS) and to compare the results with external imaging modalities, surgical palpation, and histopathologic findings. METHODS: Twenty-five patients with recurrent MTC underwent preoperative scintigraphic imaging with 500 megabecquerels (MBq) of technetium 99m(V)-dimercaptosuccinic acid [(99m)Tc(V)-DMSA] and 222 MBq of indium 111 ((111)In)-pentetreotide. The radiopharmaceutical that showed the greatest preoperative tumor uptake was selected for intraoperative RGS. Surgery was performed 24 hours after the administration of (111)In-pentetreotide or 4 hours after the injection of (99m)Tc(V)-DMSA. Furthermore, three male patients underwent surgery who suffered from recurrent pheochromocytoma (injection of 180 MBq iodine 123-labeled metaiodobenzylguanidine [(123)I-MIBG] 4--5 hours before surgery). RESULTS: Overall, lesion detection sensitivities in patients with MTC for computed tomography, (111)In-pentetreotide, and (99m)Tc(V)-DMSA were 32%, 34%, and 65%, respectively. Surgical palpation identified lymph node metastases of recurrent MTC with a sensitivity of 65%, whereas RGS localized 64 malignant lesions (sensitivity, 97%). Altogether, 71 lesions could be excised, 5 of which were adjudged false positive with respect to MTC metastases. Both surgical palpation and RGS localized all paravertebral subdiaphragmatic lesions (size > or = 2 cm) of recurrent pheochromocytoma seen in the preoperative MIBG scan. CONCLUSIONS: RGS was capable of localizing more and smaller metastases of MTC compared with conventional imaging modalities and surgical palpation. However, the relatively high radioligand accumulation in the kidneys ((111)In-pentetreotide) and the dense hepatic and biliary signals using MIBG limited their use for intraoperative detection of tumors in the area of the adrenal gland.

Retinoic acid induction of human tissue-type plasminogen activator gene expression via a direct repeat element (DR5) located at -7 kilobases.

All-trans-retinoic acid (RA) and retinoids induce synthesis of tissue-type plasminogen activator (t-PA) in endothelial and neuroblastoma cells in vitro and in rats in vivo. In HT1080 fibrosarcoma cells, induction of t-PA-related antigen secretion and t-PA mRNA steady state levels by RA were found to depend on de novo protein and mRNA synthesis. Fragments derived from the 5'-flanking region of the t-PA gene (+197 to -9578 base pairs (bp)) were linked to the chloramphenicol acetyltransferase gene. Transfection studies demonstrated that the region spanning bp -7145 to -9578 mediated induction by RA. A functional retinoic acid response element (RARE), consisting of a direct repeat of the GGGTCA motif spaced by 5 nucleotides (t-PA/DR5), was localized at -7.3 kilobases. The t-PA/DR5 element interacted with the heterodimer composed of retinoic acid receptor alpha and retinoid X receptor alpha in vitro, whereas its mutation abolished induction by RA in transient expression. In human EA.hy926 hybrid endothelial and in SK-N-SH neuroblastoma cells, the activity of t-PA/DR5 was found to be independent of the intervening sequence (-632 to -7144 bp) and of its distance from the transcription initiation site. Staurosporine, an inhibitor of protein kinase activity, inhibited induction by RA, suggesting that it required protein phosphorylation.

Reliability of reports of violent victimization and posttraumatic stress disorder among men and women with serious mental illness.

Although violent victimization is highly prevalent among men and women with serious mental illness (SMI; e.g., schizophrenia, bipolar disorder), future research in this area may be impeded by controversy concerning the ability of individuals with SMI to report traumatic events reliably. This article presents the results of a study exploring the temporal consistency of reports of childhood sexual abuse, adult sexual abuse, and adult physical abuse, as well as current symptoms of posttraumatic stress disorder (PTSD) among 50 people with SMI. Results show that trauma history and PTSD assessments can, for the most part, yield reliable information essential to further research in this area. The study also demonstrates the importance of using a variety of statistical methods to assess the reliability of self-reports of trauma history.

Characterization of mutations leading to recessive dystrophic epidermolysis bullosa and Marfan syndrome in a single patient.

Dystrophic epidermolysis bullosa (DEB) is a rare genetic skin disorder. In this report we have investigated an Italian child affected with recessive DEB (RDEB) and demonstrated that he was homozygous for the mutation R226X in the type VII collagen gene (COL7A1), leading to absence of type VII collagen at the dermal-epidermal junction. There was no family history of inherited skin blistering but the child's father was affected by Marfan syndrome, an autosomal dominant connective tissue disorder that results from mutations in the fibrillin-1 gene (FBN1). Analysis of this gene showed that the RDEB patient and his father were both heterozygous for a novel FBN1 mutation, C1971Y. This mutation affects one of the six obligate cysteine residues within one of the calcium-binding epidermal growth factor-like regions of the protein. At the age of 2-years the RDEB patient showed signs of early aortic dilatation, suggesting that he is likely to develop a Marfan syndrome phenotype in the future. This is a unique case of these two coexisting inherited disorders.

Bristow-Latarjet repair for recurrent anterior shoulder instability; an eight-year study.

A follow-up study was made of 44 patients who underwent 47 should operations as described by Bristow and Latarjet. The group consisted of 32 recurrent shoulder dislocations and 15 so-called spontaneous shoulder instabilities. The average follow-up was 3.7 years. No significant complications occurred either per- or postoperatively and relapse of luxation was not seen. Only one patient had objectively confirmed shoulder instability after the operation. The average limitation of external rotation at 90 degrees abduction was 12 degrees.