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Biological age is a better measure of functional capacity than chronological age.1 One of the measures of biological age is telomere length. Telomeres are nucleoprotein complexes that protect chromosome ends from damage. The DNA component of telomeres progressively shortens as biological age increases and thus acts as a read out for ‘miles on the biological clock’. 2 Telomere length progressively shortens as biological age increases. Within health care, ageing is almost exclusively described in terms of chronological age. Recent studies explored using biological age to stratify patients and predict outcomes.3 This project acts as a pilot study to investigate whether biological age is related to intensive care unit (ICU) outcomes and whether ICU patients age biologically at an accelerated rate. This project used blood samples from a previous study where patients underwent cardiac surgery and were admitted to the ICU. Blood samples were obtained before surgery and on days 1, 2, and 3 after surgery. The database contained the following physiological parameters: haemoglobin, urea, creatinine, RIFLE score, length of ICU stay, and whether renal replacement therapy was required. Information on co-morbidities and medication was also provided. DNA was isolated using a Maxwell machine and telomere length determined via quantitative PCR. One hundred and fifty-five blood samples from 46 patients underwent analysis. Telomere length did not differ significantly over the 4 days (P=0.662). No relationship was found between telomere length and any physiological parameter, co-morbidity, or medication. There was a trend towards significance with RIFLE score at day 3 increasing as telomere length decreased, although this was not statistically significant (P=0.09). No relationship between telomere length and the available physiological parameters, comorbidities, or medication was found. Telomere length did not vary during ICU stay. This study was limited by its small sample size. Future studies would benefit from a larger sample size; in addition, blood samples could also be obtained at 6 months after discharge to allow gradual alterations in biological age to be determined. Recent studies give evidence that telomere length is a weak biomarker of ageing,3 and that more meaningful data might be obtained using superior markers, such as CDKN2A expression or expression levels of non-coding RNAs.3

Objectif : Etudier les hospitalisations chez les autochtones et les non-autochtones pour des soins psychiatriques aigus dans le nord-ouest de l'Ontario, en 1992. Methode : Reprendre en 1992 une etude qui a eu lieu en 1986-1987 visant a comparer les hospitalisations chez les autochtones et les non-autochtones pour des soins psychiatriques aigus dans le nord-ouest de l'Ontario et examiner les inscriptions des autochtones aupres des organismes de sante mentale communautaires au cours des 6 premiers mois de 1993. Resultats : L'analyse comparative des hospitalisations a revele les suivantes : le nombre d'autochtones hospitalises depasse de 33 % le taux moyen de la population generale ; la depression semble sous-diagnostiquee chez les autochtones ; ceux-ci continuent d'etre hospitalises principalement pour des raisons autres que des troubles psychiatriques graves ; la toxicomanie et les problemes avec la loi ont souvent un role a jouer ; leur sejour a l'hopital est 2 fois plus long que celui du groupe temoin de non-autochtones ; ils sont souvent issus de milieux ruraux ; ils sont moins souvent pris en main par un service aux malades externes et plus souvent par le systeme de justice criminel. L'examen des inscriptions aupres des organismes de sante mentale communautaires a revele les suivantes : une surrepresentation similaire des autochtones ; les troubles de l'humeur et les perturbations de la pensee des autochtones de ce secteur etaient semblables a ceux des non-autochtones ; et la longueur de leur sejour etait semblable. L'hopital psychiatrique semble offrir un traitement de soins aigus non pas pour des troubles psychiatriques graves (ce qui constitue son mandat), mais pour les hospitalisations atypiques qui resultent de problemes economiques, sociaux et culturels. On soupconne un sous-diagnostic de la depression atypique chez la population autochtone hospitalisee. Lorsqu'on pose des questions sur l'origine du traitement, on apprend que le profil de diagnostic des autochtones et des non-autochtones est identique en ce qui a trait aux aspects humeur et pensee. Conclusion : Il n 'y a pas eu de changements considerables au cours de 5 dernieres annees quant au recours aux services psychiatriques hospitaliers chez les autochtones. Il se peut que les stereotypes culturels influencent le diagnostic des autochtones de facon negative. L'amelioration des programmes de controle de traitement chez les autochtones ainsi que le developpement communautaire peuvent resoudre en partie le probleme. Le redressement des mandats et des responsabilites des organismes communautaires (generiques et specifiques a une culture) permettra de reduire le nombre d'hospitalisations inutiles.

Needle localizations of radiologically suspicious but clinically impalpable breast lesions are being carried out with increasing frequency as a result of the National Breast Screening Programme. At our institution, the Nottingham Lesion Location Set (Mediplus Ltd, Bourne End, Bucks) has been used, without complication, for at least 50 such procedures (Fig. 1). It comprises an 18 gauge (G), or 21 G cannula, a fine needle localization wire which is fed through the cannula during initial positioning and a 20 G bluntended cannula which is introduced over the wire by the surgeon in theatre to facilitate identification of the wire tip. The following case report, undocumented to date, describes an unusual hazard of breast localization.

Assembling information about individuals over time allows health managers and researchers to describe the progression of diseases, the care history of individuals and the sequences of care episodes that potentially result in improving individuals' health status. However, current mental health statistics generally focus on sets of events rather than groups of individuals making it impossible to distinguish between two different persons being admitted and the same person being admitted twice. Accurate figures on treatment prevalence cannot be generated and multiservice users across time or across agencies will inflate the statistics used to plan needed services. The capacity to link consistently defined bits of information together is critical to developing a reliable information system. This article examines the adequacy of using unique identifier codes to accomplish linkage by focusing on one example of record linkage that incorporates mental health information from both community and institutional sectors in one region of Ontario, Canada. Findings indicate that unique "cradle to grave" identifiers do not guarantee accuracy if manual transcription is involved.

Exposure to solar radiation is increasingly being associated with a risk of cutaneous melanoma, and some risk has also been attributed to exposure to fluorescent lights. The risk of cutaneous melanoma associated with exposure to some sources of artificial ultraviolet radiation was examined in a case-control study in a Scottish population with fairly low exposure to natural ultraviolet radiation. The risk was not significantly or consistently raised for exposure to fluorescent lights at home or at work. The use of ultraviolet lamps and sunbeds, however, was associated with a significantly increased risk (relative risk = 2.9; 95% confidence interval 1.3 to 6.4), and the risk was significantly related to duration of use. The risk was particularly raised among people who have first used [corrected] ultraviolet beds or lamps more than [corrected] five years before presentation (relative risk = 9.1; 95% confidence intervals 2.0-40.6), in whom it was significantly related to cumulative hours of exposure. The risks associated with exposure to ultraviolet lamps and sunbeds remained significant after adjustment for other risk factors for melanoma.

Na+-selective and Ca2+-selective microelectrodes were used to examine the ionic mechanisms regulating acetylcholine (ACh) stimulation of pancreatic secretion. The cytosolic concentrations of free ionized Na+ and Ca2+ ([Na]i, [Ca]i) were determined in unstimulated acinar cells to be 10.5 +/- 0.4 mM and 0.43 +/- 0.03 microM, respectively. By measuring the induced changes in intracellular Ca2+, Na+, and membrane potentials (ECa, ENa, Em), we were able to demonstrate that 5 X 10(-8) M ACh depolarized Em by 4.3 +/- 0.2 mV and increased [Na]i and [ca]i to 12.2 +/- 0.3 mM and 0.58 +/- 0.02 microM, respectively. Stimulation with ACh at concentrations ranging from 10(-8) to 10(-5) M increased [Ca]i from 0.4 microM to between 0.5 and 1.0 microM. Amylase release reached a maximum at 10(-7) M ACh stimulation and progressively decreased at higher concentrations of stimulus. Increasing the stimulus above an optimal concentration appears to reduce or inhibit enzyme release. These experiments provide direct evidence supporting the concept that acinar cell secretion is triggered by increases in [Ca]i and of calcium's ability to act as primary intracellular mediator. Stimulation after removal of extracellular Ca2+ eliminated the increase in [ca]i that is usually observed in secreting cells, while producing the normal depolarization of Em and increase in [Na]i. These studies demonstrate the increases in [Ca]i are derived from an increase in membrane permeability to Ca2+ and the ability of ACh to depolarize the Em by a transmembrane movement of Na+ that is independent of the change in intracellular Ca2+.

As the ionophore A23187 is believed to act by increasing cytosolic Ca2+ ([Ca]i), it offers a mechanism for experimentally controlling [Ca]i. Ca2+-selective microelectrodes were employed to examine the effect of A23187 on [Ca]i and the role of [Ca]i in acinar secretion. The mean [Ca]i in acinar cells of the mouse pancreas was determined to be 0.43 +/- 0.03 microM. When the ionophore was added to the saline bathing the acinar cells, 10(-6) M A23187 depolarized the membrane potential (Em) by 5.2 +/- 0.3 mM and the intracellular Ca-electrode potential (ECs) by 9.8 +/- 0.6 while 10(-5) M A23187 depolarized Em by 7.4 +/- 0.3 mV and ECs by 14.1 +/- 0.8. These changes in potentials reflect an increase in [Ca]i to 0.62 +/- 0.03 microM with 10(-6) M and 0.73 +/- 0.05 microM with 10(-5) M A23187. The increase in [Ca]i observed with 10(-6) M A23187 was similar to that found with concentrations of acetylcholine (Ach) that produced maximal enzyme secretion, whereas the increase in [Ca]i with 10(-5) M was similar in magnitude to that observed with ACh concentration that inhibited or reduced secretion. Measurements of amylase release during 30 min exposure of A23187 produced an 88.4% increase in amylase activity over basal levels with 10(-6) M and little or no change with (10(-5) M, indicating that the ionophore influences secretion through changes in [Ca]i in a manner analogous to the natural secretagogue ACh. This report establishes that acinar secretion occurs only within a narrow range of [Ca]i activities and suggests intracellular increases in both "bound" and "free" calcium may occur during cell activation.

To explain the improved survival rates of females with malignant melanoma compared with that of males in this region of the United Kingdom (a recognized low incidence area for melanoma), clinicopathologic differences between the sexes of 477 patients presenting with primary melanoma at all stages, were examined between 1961 and 1976. The survival of 356 males and females presenting with Stage I melanoma were also compared, taking death from melanoma as the critical event. The data were analyzed using the Cox multivariate model, which allows several prognostic variables to be considered simultaneously, and enabled the assessment of the effect of, and interactions between, these variables. Female superiority in survival was due to: (1) more lesions on the female lower limb, a site associated with a good prognosis; (2) thinner lesions at presentation in the female; (3) an interaction with age in which females between the age of 50 and 79 years fare significantly better than a similar age group of males. This age/sex interaction has not been observed in high incidence areas. It suggests, therefore, that melanoma may behave differently in different geographical areas.Cancer 58:788-792, 1986.

A multicentre case-control study of 216 patients with palmoplantar pustulosis and 626 controls with miscellaneous dermatoses showed a considerably higher prevalence of smoking in the group with palmoplantar pustulosis. This was the first indication that smoking may be an important factor in this skin disease, possibly by affecting the inflammatory responses of the skin.

Electrophysiological studies were undertaken to determine the transmembrane and transepithelial changes in free Ca2+ concentration that occur during serotonin-induced secretion in the salivary glands of the blowfly, Phormia regina. Ca-selective and conventional microelectrodes were used to measure intracellular and luminal Ca2+ concentrations ([Ca]L), serosal membrane and transepithelial potentials (Em, Etr), and their changes during serotonin (5-hydroxytryptamine, 5HT)-induced salivary secretion. The effect of stimulus concentration on these parameters and enzyme release was also determined. Previous studies provided evidence that serosal stimulation with 10(-8) M 5HT caused a hyperpolarization of Em and short phasic two- to threefold increases in [Ca]i. In these studies, higher concentrations of 5HT (10(-7) M) resulted in depolarization of Em by 13 +/- 1.2 mV and of ECa by 64 +/- 2.1 mV, a dramatic increase in [Ca]i, and a decrease in enzyme release. In addition, serotonin (10(-8) M) reduced the normal spontaneous Etr (+19.6 +/- 1 mV) to near zero while causing an increase in [Ca]L from 1.3 +/- 0.3 X 10(-5) mM to 2.0 +/- 0.1 X 10(-3) mM, a concentration isomolar with that of the bathing medium. These results provide direct electrochemical evidence that, during stimulus-secretion coupling of the salivary epithelial cells, the neurohormone serotonin controls the secretory response by the regulation of intracellular Ca2+ and induces transepithelial transport of Ca2+, thereby suggesting that, during secretion, the neurohormone causes the salivary gland to behave as a "leaky epithelium" by activating the paracellular shunt pathways.

Enzyme preparations were isolated from post-mortem adrenal tissue of a patient with lipoid adrenal hyperplasia and normal human- and bovine adrenal tissue. Cholesterol-cleaving properties were studied in incubation experiments with the addition of appropriate substrates. Cholesterol-cleaving activity of enzyme preparations of adrenal tissue from the patient was extremely low as compared with normal controls. There was no difference in 20α-hydroxycholesterol-cleaving activity. There is thus evidence for a deficient 20α-cholesterol-hydroxylase activity in the adrenal tissue of this patient with lipoid adrenal hyperplasia.

Examination of 180 patients with cutaneous malignant melanoma and 197 control patients in a case-control study showed that the risk of melanoma is strongly related to numbers of benign melanocytic naevi (moles). Some unusual features of naevi--a diameter exceeding 7 mm, colour variation, and irregular lateral outline--also showed a strong association with the risk of melanoma, but the relation of numbers of naevi to risk was present even in the group of patients whose naevi had none of these unusual features. Biopsy of clinically atypical naevi from several of the patients at highest risk generally did not show dysplastic histology. Thus a group of people at high risk of melanoma may be identified by using simple clinical assessment of naevi.

The action of insulin on the resting membrane potential (Em) and intracellular sodium and potassium activities (aNa, aK) of rat soleus muscle fibers was determined by direct intracellular measurements of aNa, aK, and Em using Na-selective, K-selective, and conventional microelectrodes. The use of these microelectrodes allowed us to continuously monitor these parameters in the same fiber. Although we were able to accurately measure aNa and aK and continuously monitor their levels throughout periods of insulin stimulation of up to 20 min duration, we were unable to detect any significant change in Em, aNa, or aK. Varying the concentration of insulin or extracellular glucose failed to alter our observations. These results indicate that the action of insulin on the sarcolemma and subsequent increase in glucose transport must result from some mechanism independent of a change in membrane potential or intracellular sodium or potassium activity.

Ion-selective microelectrodes were employed to determine the electrochemical driving forces involved in the transepithelial transport of Na+ and Cl- during acetylcholine (ACh) stimulation of pancreatic acinar cells. In HCO-3-free Ringer solution, the mean values of intracellular Cl and Na activities (aiCl and aiNa) were 68.9 +/- 1.1 and 8.3 +/- 0.3 mM, respectively. The mean value of aiCl is above the calculated equilibrium value, indicating that Cl entry into the cell is an energy-requiring process. Continuous measurement of intracellular electrode potentials during stimulation of the cells with concentrations of ACh ranging from 10(-7) to 10(-5) M demonstrated the neurotransmitter's influence on transmembrane Na+ and Cl- movement in secreting cells. The mean values of the induced changes in aiCl and aiNa at every concentration of ACh measured were not significantly different (P greater than 0.5), although the mean changes in either aiNa or aiCl determined with every decade change in ACh concentration were significant (P less than 0.05). The transmembrane Na+ electrochemical gradient dissipated with the induced increases in aiCl. These results suggest that, during stimulus-secretion coupling of pancreatic acinar cells, there is a transcellular route for NaCl secretion, and the energy for NaCl entry into the cell may be derived from the Na+ electrochemical gradient that exists across the basolateral epithelial membrane. They also suggest that the ACh-induced changes in ionic permeability of the plasma membrane may be the coupling mechanism by which the simultaneous events enzyme release and electrolyte secretion are controlled in stimulated cells.

In a study of risk factors for the development of melanocytic naevi in relation to the pathogenesis of malignant melanoma 197 white adults were examined by four dermatologists and naevus counts correlated with several other features. Highly significant associations were found between large numbers of banal acquired melanocytic naevi and the ability to tan easily without burning (skin types 3 and 4; relative risk 4.6), brown or hazel eyes (relative risk 3.5), green or grey eyes (relative risk 3.5) and brown or black hair (relative risk 3.7). No significant associations with numbers of naevi were shown for parity or use of oral contraceptives or other steroid hormones. This is the first study to find any relation between melanocytic naevi and phenotypic factors in a white population.

The term ermine phenotype has been chosen to describe patients with white hair with black tufts. The patients also have sensorineural hearing loss. This rare phenotype may come about either by failure of migration of melanocytes or by an autoimmune mechanism. Examples of each are cited. The authors describe a possible third type. Comparison with other pigment loss-sensorineural hearing loss syndromes is made.

We present some new analyses of data from the Western Canada Melanoma Study [1–3], based on 595 subjects with melanoma, excluding lentigo, and community controls. The validity of the study has been checked; interviewed patients do not differ from non-interviewed patients in pathological type, stage, or age, and the control group is virtually identical to the census populationon variables where this can be assessed. For many exposures, the proportions of patients and controls giving positive replies are virtually identical, suggesting no major response bias.

A case of hepatopulmonary hydatid disease in a Cypriot who presented with pyogenic infection with Streptococcus milleri is described. Although hydatid disease and pyogenic liver abscess are both rare in the UK, an underlying echinococcal pathology should be suspected in any patient from an area endemic for hydatid who presents with a pyogenic hepatic or hepatopulmonary abscess.

SUMMARY The clinical features of two female infants with incontinentia pigmenti and evidence of neurological abnormality are described. In one infant a neuropathological examination revealed a prenatal malformation of the cerebral cortex (micropolygyria) and unilateral pyramidal hypoplasia. There were also signs of a destructive process which had occurred later in development and which was characterised by some small cavities in the central white matter, sclerotic atrophy of a few cerebral gyri and patchy foci of neuronal loss in the cerebellum. RESUME Les auteurs decrivent les caracteristiques cliniques de deux nouveaux nes du sexe feminin avec incontinentia pigmenti et evidence de malformation neurologique. Chez un des nouveaux nes un examen neuropathologique a revele une malformation prenatale du cortex cerebral (micropolygyrie) et une hypoplasie pyramidale unilaterale. Il y avait aussi des signes d'un processus de destruction qui etait survenu a un stade plus tardif du developpement et qui etait caracterise par de petites cavites dans la matiere blanche centrale, l'atrophie sclerotique de quelques circonvolutions cerebrales et des foyers irreguliers de perte des neurones dans le cervelet. ZUSAMMENFASSUNG Die klinischen Merkmale zweier weiblicher Kleinkinder mit incontinentia pigmenti und neurologischen Anomalien werden beschrieben. Bei einem der Kleinkinder ergab die neuropathologische Untersuchung eine praenatale Anlagestorung der Hirnrinde (Micropolygyrie) mit einseitiger Hypoplasie der Pyramiden. Es fanden sich auch Anzeichen eines destruktiven Vorganges, der wahrend eines spateren Entwicklungsstadiums aufgetreten war mit kleinen Hohlraumbildungen in der weissen Substanz, mit sklerotischer Atrophie einiger Hirnwindungen und mit herdformigem Untergang von Neuronen im Kleinhirn. RESUMEN Se describe el cuadro clinico de dos lactantes afectas de incontinentia pigmenti con evidencia de anormalidad neurologica. En una de las lactantes un examen neuropatologico revelo una malformacion cerebral (micropoligira) e hipopoplasia piramidal unilateral. Habia tambien signos de un proceso destructwo que habia ocurrido mas tarde en el desarrollo y que caracterizaban unas cavidades pequenas en la materia blanca central, atrofia esclerorica de algunas de las circunvoluviones cerebrales, y focos esparcidos de dano neuronal en el cerebelo.

We have carried out a case control study on 200 patients presenting in the past 3 years with primary cutaneous malignant melanoma and 200 age- and sex-matched controls. Total body melanocytic naevus counts were performed on all 400 subjects by four trained dermatologists. Analysis was by stratum matched logistic regression, with stratum matching for age, sex and city of treatment. Each variable was adjusted for the other risk factors found in the study, such as hair and eye colour, skin type, amount of UV exposure and episodes of acute sunburn. Substantially increased risk of malignant melanoma was found for persons with large numbers of normal benign melanocytic naevi, with any moles larger than 7 mm in diameter, and also with irregular edges and colour variation in moles—the so-called dysplastic naevi. The number of moles present on the same anatomical areas as the tumour (arms, legs, trunk, face, head and neck, and palms and soles) was a stronger predictor of melanoma incidence than was the total number of body moles. The relationship of histology and Breslow thickness of melanoma to site, sex, age and number of naevi will also be presented. Our results show that a very high-risk group for melanoma can now be identified and these patients should be advised about avoiding excessive sun exposure and the early recognition of cutaneous melanoma.