Making time for what's important: what elements should we value when planning practice-based professional training?

Newly qualified professional healthcare graduates, whether training to become doctors, dentists, veterinary surgeons or nurses, tend to need some support as they take their first steps along that bumpy road from university to confident, competent practice. We identify some key features of the UK programme of dental practice-based training to acknowledge its strengths - 12 months of clinical practice within a well-established dental team, one-to-one weekly meetings with the same dedicated mentor, regular peer learning with the same group of peers over 12 months and the opportunity to observe role models from the profession including training programme directors and other general dental practitioners (GDPs). This educational programme is unique to dentistry and this article outlines why we believe it is important to value these features when designing postgraduate professional training in healthcare sciences.

A retrospective study of peanut and tree nut allergy: Sensitization and correlations with clinical manifestations.

Peanut (PN) and tree nut (TN) allergies are among the leading causes of fatal food-induced anaphylaxis and are increasing in prevalence, especially in children. Their cosensitization and concurrent clinical allergy have been understudied. This retrospective study investigated the correlation between PN and TN allergy, both in terms of in vitro sensitization (IVS) and clinical allergic manifestations. We conducted a retrospective medical record review at the Allergy Clinic at University Hospital of Brooklyn. Fourteen hundred six charts were reviewed, of which 76 (5.4%) had documented relevant clinical allergy: PN allergy but not TN allergy (n = 29) or TN allergy but not PN allergy (n = 11) or both (n = 30). Six patients with PN allergy but no TN exposure history were not included in the analysis. The majority of patients (67/76, 88.1%) had a concurrent history of asthma, rhinoconjunctivitis, or AD. Sensitivity of TN IVS predicting PN IVS was 38/39 (97%). Similarly, sensitivity of PN IVS predicting TN IVS was 38/42 (91%). Sensitivity of TN clinical allergy predicting PN allergy was 30/59 (51%). Sensitivity of PN clinical allergy predicting TN allergy was 30/41 (73%). The total number of organ systems involved in reported clinical reactions correlated with IVS to TN (p = 0.004) but not IVS to PN (p = 0.983). In summary, we found PN sensitization predicts TN sensitization in vitro, with lower predictability for clinical reactions.

Mutations in AEC syndrome skin reveal a role for p63 in basement membrane adhesion, skin barrier integrity and hair follicle biology.

BACKGROUND: AEC (ankyloblepharon-ectodermal defects-clefting) syndrome is an autosomal dominant ectodermal dysplasia disorder caused by mutations in the transcription factor p63. Clinically, the skin is dry and often fragile; other features can include partial eyelid fusion (ankyloblepharon), hypodontia, orofacial clefting, sparse hair or alopecia, and nail dystrophy. OBJECTIVES: To investigate how p63 gene mutations affect gene and protein expression in AEC syndrome skin. METHODS: We performed microarray analysis on samples of intact and eroded AEC syndrome skin compared with control skin. Changes were verified by quantitative real-time reverse transcription-polymerase chain reaction and, for basal keratinocyte-associated genes, by immunohistochemistry and analysis of microdissected skin. RESULTS: We identified significant upregulation of six genes and downregulation of 69 genes in AEC syndrome skin, with the main changes in genes implicated in epidermal adhesion, skin barrier formation and hair follicle biology. There was reduced expression of genes encoding the basement membrane proteins FRAS1 and collagen VII, as well as the skin barrier-associated small proline-rich proteins 1A and 4, late cornified envelope protein 5A, hornerin, and lipid transporters including ALOX15B. Reduced expression of the hair-associated keratins 25, 27, 31, 33B, 34, 35, 81 and 85 was also noted. We also confirmed similar alterations in gene expression for 26 of the 75 genes in eroded AEC scalp skin. CONCLUSIONS: This study identifies specific changes in skin structural biology and signalling pathways that result from mutant p63 and provides new molecular insight into the AEC syndrome phenotype.

Rapp-Hodgkin and Hay-Wells ectodermal dysplasia syndromes represent a variable spectrum of the same genetic disorder.

BACKGROUND: Rapp-Hodgkin syndrome (RHS) and Hay-Wells [also known as ankyloblepharon-ectodermal defects-cleft lip/palate (AEC)] syndrome have been designated as distinct ectodermal dysplasia syndromes despite both disorders having overlapping clinical features and the same mutated gene, TP63. OBJECTIVES: To search for TP63 mutations in two unrelated cases of RHS and two of AEC syndrome and to review the TP63 mutation database and clinical descriptions of affected individuals, the goal being to refine genotype-phenotype correlation and to determine the clinical/molecular justification for RHS and AEC continuing to exist as separate entities. METHODS: Clinical examination of four affected cases and sequencing of genomic DNA using TP63-specific primers. Literature review of published clinical descriptions of RHS and AEC syndrome cases containing TP63 mutation data. RESULTS: Cases of RHS and AEC show considerable clinical overlap, particularly with regard to hypotrichosis and mid-face hypoplasia, and the clinical feature of ankyloblepharon in AEC is often subtle, transient and a poor distinguishing clinical sign. We identified two new and two recurrent heterozygous mutations in TP63: c.1456insA (p.Leu486fsX52), RHS; c.1537T>G (p.Phe513Val), RHS; c.1787delG (p.Gly596fsX68), AEC; and c.1682G>A (p.Gly561Asp), AEC. Including this study, 42 different mutations in TP63 in RHS and AEC have now been reported, three of which are exactly the same in both syndromes. CONCLUSIONS: Our clinicopathological and molecular findings indicate that there is no justification for the continued use of eponyms in referring to these particular ectodermal dysplasia syndromes. We support the view that the terms 'Hay-Wells' and 'Rapp-Hodgkin' should be abandoned in favour of the all-inclusive diagnosis 'AEC syndrome', notwithstanding the inconsistency or often transient nature of the ankyloblepharon.

Molecular basis of EEC (ectrodactyly, ectodermal dysplasia, clefting) syndrome: five new mutations in the DNA-binding domain of the TP63 gene and genotype-phenotype correlation.

Summary EEC (ectrodactyly, ectodermal dysplasia, clefting; OMIM 604292) syndrome is an autosomal dominant developmental disorder. Characteristic clinical features comprise abnormalities in several ectodermal structures including skin, hair, teeth, nails and sweat glands as well as orofacial clefting and limb defects. Pathogenic mutations in the TP63 transcription factor have been identified as the molecular basis of EEC syndrome and to date 34 mutations have been reported. The majority of mutations involve heterozygous missense mutations in the DNA-binding domain of TP63, a region critical for direct interactions with DNA target sequences. In this report, we present an overview of EEC syndrome, discuss the role of TP63 in embryonic development and skin homeostasis, and report five new TP63 gene mutations. We highlight the significant intra- and interfamilial phenotypic variability in affected individuals and outline the emerging paradigm for genotype-phenotype correlation in this inherited ectodermal dysplasia syndrome.

PORCN gene mutations and the protean nature of focal dermal hypoplasia.

Focal dermal hypoplasia (FDH) is an X-linked dominant disorder featuring developmental abnormalities of ectodermal and mesodermal tissues. Pathogenic mutations in the PORCN gene (locus Xp11.23) were identified in 2007 and thus far 27 different mutations have been reported. PORCN encodes a putative O-acyltransferase which facilitates secretion of Wnt proteins required for ectomesodermal tissue development. We investigated PORCN gene pathology and pattern of X-chromosome inactivation analysis in two unrelated Caucasian female patients who presented with multiple developmental abnormalities consistent with FDH. We also reviewed the clinical and molecular data for all reported PORCN mutations and assessed genotype-phenotype correlation for sporadic and familial cases of FDH. DNA sequencing revealed two new PORCN gene mutations: p.W282X and c.74delG (p.G25fsX51). X-chromosome inactivation analysis revealed a random pattern in one case but was uninformative in the other. Collectively, point/small mutations account for 24 out of the 29 PORCN mutations and are typically seen in sporadic cases; larger deletions are more common in familial cases. Identification of two new PORCN gene mutations confirms the importance of PORCN-associated Wnt signalling in embryogenesis. Both new cases showed Blaschko-linear dermal hypoplasia and extensive ectomesodermal abnormalities, including severe limb developmental anomalies and a giant cell tumour of bone in one patient. Clinical variability can be attributed to the degree of lyonization and postzygotic genomic mosaicism, which are important mechanisms in determining the clinical presentation.

Localized bullous pemphigoid in a patient with primary lymphoedema tarda.

We report a case of localized bullous pemphigoid (BP) in a woman patient with primary lymphoedema tarda. There is only one previous case reported of localized pemphigoid in an area of lymphoedema, this being of the cicatricial variant. Slow circulation in the lymphatic vessels, increased capillary permeability with preferential localization of antibodies in the area, and potential cleavage of the epidermal junction due to increased hydrostatic pressure leading to autoimmunity, have all been advocated as possible pathogenic mechanisms. Nevertheless, we consider that the mechanism by which localized pemphigoid arises on lymphoedema remains elusive, based on a previous case of generalized BP sparing an area of postsurgical lymphoedema.

Chronic administration of fluoxetine alters locomotor behavior, but does not potentiate the locomotor stimulating effects of CRH in juvenile Chinook salmon (Oncorhynchus tshawytscha).

The present study investigated: 1) the behavioral effects of chronic administration of a serotonin uptake inhibitor (fluoxetine) in juvenile Chinook salmon, Oncorhynchus tshawytscha and, 2) whether chronic administration of fluoxetine alters the behavioral effects of corticotropin-releasing hormone (CRH). Chronic (20 day) treatment with fluoxetine decreased locomotor activity when compared to fish given long-term injections of saline. An intracerebroventricular (i.c.v.) injection of CRH had no effect on locomotor activity following a 20 day intraperitoneal treatment with either saline or fluoxetine. Chronic treatment with fluoxetine also increased the amount of time fish spent near the center of the tank. A similar increase was seen in fish given a chronic intraperitoneal (i.p.) series of saline followed by an acute i.c.v. injection of CRH. However, the effect was not additive when fish were given chronic i.p. injections of fluoxetine followed by an acute i.c.v. injection of CRH. These results provide evidence to support the hypothesis that the serotonergic system is involved in mediating locomotor activity and habitat choice in teleosts.

Comparison of the amniotic fluid index with gray-scale and color Doppler ultrasound.

OBJECTIVES: This study was undertaken to compare the amniotic fluid index (AFI) obtained with gray-scale ultrasound and color Doppler. STUDY DESIGN: We examined 77 patients ranging from 22 to 41 weeks' gestation with two of five sonographers obtaining two measures of the AFI utilizing gray-scale and color Doppler. RESULTS: Of the measurements of AFI, 96% showed the gray scale measurement to be greater than the color measurement (p < 0.0001; mean 9.3 +/- 3.3 cm vs. 8.5 +/- 3.0 cm). At gray-scale AFI < 5 cm, color AFI was essentially the same, but at gray-scale AFI 5-10 cm, color AFI was < 5 cm, 15.2% and 7.8% of the time. At gray-scale AFI > 10 cm, no color AFI was < 5 cm. Individual (n = 5) interobserver reliability was r = 0.79 (p < 0.0001) and intraobserver reliability was r = 0.94 (p < 0.0001). CONCLUSIONS: AFI by color Doppler was always less than with gray scale. At an AFI of 5-10 cm, color demonstrated an AFI of < 5 cm in up to 16% of patients, and increased the diagnosis of oligohydramnios.

Transesophageal echocardiography: not an innocuous procedure.

We report 3 patients who sustained intrathoracic esophageal perforations due to transesophageal echocardiography encountered during the past 2 years. Lack of suspicion of this complication led to delay in diagnosis. Surgical management led to survival of all 3 patients.

Volumetric umbilical artery blood flow: comparison of the normal versus the single umbilical artery cord.

OBJECTIVE: This was a study of the volumetric blood flow in single umbilical artery (SUA) cords as compared to three-vessel cords. HYPOTHESIS: SUA flow will be twice that of an artery in a normal cord. METHODS: We studied 276 patients (24 SUA, 252 normal cord) at 18-40 weeks' gestation utilizing gray-scale and color Doppler. Flow, flow/kg, velocity, artery diameter, Doppler velocimetry indices, estimated fetal weight (EFW) and amniotic fluid index (AFI) were compared. All fetuses were anatomically and cytogenetically normal. RESULTS: Blood flow increased with advancing gestation and the SUA volume was twice that in the normal cord artery. Flow/kg decreased for both cords, with the SUA values twice those of normal cords. Arterial diameter and velocity increased, but to a greater degree in SUA. Velocimetry, although in the normal range, decreased progressively with the resistance indices always lower in the SUA cord. EFW and AFI were the same for both groups. CONCLUSION: Volumetric blood and its components were measured indirectly with ultrasound. The SUA cord artery carried twice the blood volume of an artery in a three-vessel cord. Other flow parameters changed appropriately to explain the increased flow. For the anatomically normal fetus with SUA there was no increase in intrauterine growth restriction.

Inhibition of tendon cell proliferation and matrix glycosaminoglycan synthesis by non-steroidal anti-inflammatory drugs in vitro.

The purpose of this study was to investigate the effects of some commonly used non-steroidal anti-inflammatory drugs (NSAIDs) on human tendon. Explants of human digital flexor and patella tendons were cultured in medium containing pharmacological concentrations of NSAIDs. Cell proliferation was measured by incorporation of 3H-thymidine and glycosaminoglycan synthesis was measured by incorporation of 35S-Sulphate. Diclofenac and aceclofenac had no significant effect either on tendon cell proliferation or glycosaminoglycan synthesis. Indomethacin and naproxen inhibited cell proliferation in patella tendons and inhibited glycosaminoglycan synthesis in both digital flexor and patella tendons. If applicable to the in vivo situation, these NSAIDs should be used with caution in the treatment of pain after tendon injury and surgery.

96-well plate-based method for total collagen analysis of cell cultures.

Total collagen assays are often laborious and use large quantities of consumables. We have developed a new method of assaying total 3H-proline-labeled collagen from cultured cells. Cells and media are harvested from 96-well plates directly onto fiberglass filtermats and counted in the Wallac 1205 flat-bed scintillation counter (BetaPlate). The assay was validated by comparison with a traditional total collagen assay. The resulting assay provides a rapid one-step method for quantifying collagen synthesis, which, unlike many collagen assays, does not require extensive dialysis or precipitation of proteins.

The role of transesophageal echocardiography in the diagnosis and management of patients with aortic perivalvular abscesses.

Aortic valve abscesses (AVAs) are a devastating complication of aortic valve endocarditis. Over 8 years, 25 patients were diagnosed with AVA by transesophageal echo (TEE). Management and outcomes were then analyzed. Eleven (44%) AVAs involved prosthetic valves, and 6 (24%) occurred in congenitally malformed valves. Twenty patients (80%) underwent surgical intervention; the rest were treated medically. Eleven (44%) of the patients died [6 (30%) surgery patients and all the medical patients]. Eight of 11 (73%) patients who died were culture positive for Staphylococcus aureus. All patients with congenitally malformed aortic valves underwent surgical intervention and survived. We conclude that: (1) despite advances in therapy and diagnosis, patients with AVAs have a high mortality rate; (2) prognosis with AVA is especially poor when S aureus is the infectious organism; (3) patients with AVAs in congenitally malformed valves have a great outcome with surgery; (4) patients treated medically have a very poor prognosis; earlier identification by TEE may be critical to improving survival.

Volumetric flow in the umbilical artery: normative data.

OBJECTIVE: Provide normative data for the volumetric blood flow (cc/min and cc/min/kg) in the umbilical artery. METHODS: Flow was determined from an umbilical artery in 252 normal obstetrical patients from 18-40 weeks' gestation utilizing pulsed Doppler and color flow Doppler with an angle of insonation of 30-60 degrees. Simultaneous velocimetry studies (S/D ratio, resistance and pulsatility indices), fetal biometry, and an anatomic survey were obtained to further define the normal population. RESULTS: There was a steady increase in the flow (cc/min) in the umbilical artery as pregnancy progressed. Flow/kg showed a steady decline as fetal weight increased. Umbilical artery diameter increased until reaching a plateau at 32-34 weeks. Velocimetric results were consistent with known data. CONCLUSIONS: Volumetric blood flow in the umbilical artery can be determined with relative ease and normative data from 18-40 weeks is presented for the first time.

Transesophageal echocardiography detection of an esophageal sarcoma mimicking aortic dissection.

This report shows that transesophageal echocardiography can detect thoracic pathology, in this case esophageal sarcoma, as well as cardiac and aortic abnormalities. Transesophageal echocardiography can help differentiate cardiac from aortic or other intrathoracic pathology when the patient's history and physical examination do not provide enough information.

Internal mammary artery perfusing the Leriche's syndrome.

Two cases of collateral perfusion of a lower extremity, by way of an internal mammary artery, in the presence of Leriche's syndrome are described. The importance of recognizing this condition prior to coronary artery bypass grafting is emphasized.