Clinical correlation and molecular evaluation confirm that the MLH1 p.Arg182Gly (c.544A>G) mutation is pathogenic and causes Lynch syndrome

Approximately 25 % of mismatch repair (MMR) variants are exonic nucleotide substitutions. Some result in the substitution of one amino acid for another in the protein sequence, so-called missense variants, while others are silent. The interpretation of the effect of missense and silent variants as deleterious or neutral is challenging. Pre-symptomatic testing for clinical use is not recommended for relatives of individuals with variants classified as ‘of uncertain significance’. These relatives, including non-carriers, are considered at high-risk as long as the contribution of the variant to disease causation cannot be determined. This results in continuing anxiety, and the application of potentially unnecessary screening and prophylactic interventions. We encountered a large Irish Lynch syndrome kindred that carries the c.544A>G (p.Arg182Gly) alteration in the MLH1 gene and we undertook to study the variant. The clinical significance of the variant remains unresolved in the literature. Data are presented on cancer incidence within five kindreds with the same germline missense variant in the MLH1 MMR gene. Extensive testing of relevant family members in one kindred, a review of the literature, review of online MMR mutation databases and use of in silico phenotype prediction tools were undertaken to study the significance of this variant. Clinical, histological, immunohistochemical and molecular evidence from these families and other independent clinical and scientific evidence indicates that the MLH1 p.Arg182Gly (c.544A>G) change causes Lynch syndrome and supports reclassification of the variant as pathogenic.     

Incidental finding of a true human tail in an adult: a case report

True human tails are rare vestigial structures that are typically removed in childhood. Here a case is presented in which an inconspicuous sacrococcygeal tail was incidentally discovered in late adulthood. A 56‐year‐old man with no significant past medical history presented to a dermatology clinic with a chief complaint of a hyperpigmented lesion on his central back. However, on full body skin exam, a separate flesh‐colored 0.7 cm × 0.5 cm appendage was discovered in the midline sacrococcygeal region. This lesion had been present and unchanged since childhood. This particular lesion was removed via shave biopsy. Microscopic exam found it to be consistent with a diagnosis of a true human tail. There were no apparent involved spinal cord structures, and no further treatment was thought to be necessary. Human tails are congenital anomalies associated with occult spinal lesions in about 50% of cases. Therefore, it is in these patients' best interest to thoroughly evaluate for spinal cord involvement prior to biopsy. There is a relative lack of literature published on the topic, and a greater awareness of human tails would be helpful to ensure their inclusion in a differential diagnosis for persistent sacrococcygeal lesions in patients of any age.     

Nursing prioritization of the patient need for care: A tacit knowledge embedded in the clinical decision-making literature

Every day in clinical settings, nurses practise in complex and dynamic situations. Nurses work to achieve emergent order in these situations through nursing prioritization of the patient need for care. As direct research on nursing prioritization had not been reported, a study, using critical realism as method, was designed to discern the profession's embedded understanding from within the clinical decision-making literature. The research synthesizes a tacit knowledge on nursing prioritization of the patient need for care from key international literature (from 1966 to 2003). Nursing prioritization was discerned in both education and practice literatures; interrelationships between these and theoretical approaches were also identified. Nursing prioritization of the patient need for care was revealed both as a non-sequential decision-making process throughout unfolding patient situations and as an advanced skill of nursing practice. Increasing confidence with this skill is the hallmark of developing expertise.     

The use of reflection in a palliative care programme: a quantitative study of the development of reflective skills over an academic year

The use of reflection in a palliative care programme: a quantitative study of the development of reflective skills over an academic year Reflection has gained a reputation for encouraging the integration between theory and practice within professional education. However, this reputation is based on an evidence base that mostly consists of theoretical debate. The aim of this study was to test our experience that the ability to reflect is developmental and that some reflective skills are harder to achieve than others. The research was undertaken by assessing the degree to which registered nurses achieved reflective criteria within assignments submitted for a variety of palliative care undergraduate modules. A total of 160 assignments were analysed using a marking grid constructed from a literature review and the results were compared between students and across academic terms. The results suggest that students are able to describe their practice but find it harder to analyse knowledge, the context of care and to action plan. Nevertheless, reflective abilities developed over time with significant developments made between each term. However, the development of skills indicative of critical reflection was less evident and confined to the ability to raise implications for future learning. The lack of multivariate analysis limits the study. However, the findings build on previous research and prompt questions for future work, particularly with respect to the process of reflection and how this can be supported in order to encourage the development of critical reflective skills.     

Microphonic versus end-tidal carbon dioxide nasal airflow detection in neonates with apnea

Impedance pneumography in combination with expired CO2 monitoring are commonly used techniques for detecting central and obstructive apnea in infants. In this investigation an American Telephone and Telegraph StarSet-1 3000-ohm self-actuating microphone connected to the end of an infant cannula was used to monitor neonatal nasal airflow to detect breaths and apnea. The microphone was placed in a soundproof container to eliminate environmental sound artifacts. Analyses of 100 breaths from five patient samples during active and quiet sleep showed that there was no significant difference between microphone and expired CO2 recording of respiration. The techniques were 98% and 96% sensitive, respectively. Microphonic detection of nasal airflow identified 27 of the 32 episodes of upper airway obstruction (84.2%) registered by end-tidal CO2 recording. Inspiratory and expiratory events could also be well documented. Microphonic recording of nasal airflow is a reliable and inexpensive technique to detect apnea.     

Thyroid dysfunction in Down's syndrome.

One hundred and sixteen children with Down''s syndrome, living in the community, were examined for clinical or laboratory evidence of thyroid dysfunction. Three were hypothyroid and one was hyperthyroid. Twenty eight (29%) had thyroid autoantibodies. Autoimmune conditions were present in first or second degree relatives of 35 (30%) of the children, and in 17 (15%) this was a thyroid disorder. The families of normal control children also showed a 30% incidence of overt autoimmune conditions, and 19 (16%) families showed overt thyroid disease.     

Paediatric telephone consultation--a neglected area of health service delivery

Telephone enquiries to a large paediatric institution were monitored over a 4 week period. Of the 1764 calls handled during this period (an average of 63 per day), over 75% sought advice regarding symptoms of illness in their children. The commonest were to do with vomiting and diarrhoea, fever, infectious disease, respiratory symptoms and feeding problems. It is suggested that it is no longer appropriate for such calls to be handled in an ad hoc manner as is the custom in most hospitals, but that specific telephone protocols be developed and evaluated to address this important area of paediatric consultation.     

Efficacy of repeated doses of ivermectin against Mansonella perstans

Treatment of Mansonella perstans infection, although seldom necessary, is difficult. In a 3 year's trial of normal and high-dose annual and 3-monthly ivermectin treatment against Onchocerca volvulus, the effects on M. perstans were recorded and related to the cumulative dose received. The World Health Organization's African Programme for Onchocerciasis Control may thus reduce the endemicity of M. perstans.