Autoimmunity to insulin, beta cell dysfunction, and development of insulin-dependent diabetes mellitus

Circulating insulin autoantibodies (INSAAb) were measured in discordant monozygotic twins, first-degree relatives, and other groups at "high risk" for the development of insulin-dependent diabetes mellitus (IDDM), and these results correlated with both islet cell antibody (ICAb) status and beta cell function. INSAAb were positive in 31.6% (12 of 38) ICAb-positive subjects but in only 3.1% (3 of 97) ICAb-negative subjects (X2 = 22.4; P less than 0.001). Elevated levels of INSAAb tended to correlate with younger age and were observed in individuals irrespective of the prevailing degree of their beta cell function. Eight of 15 subjects detected to be INSAAb positive have thus far progressed to clinical IDDM (X2 = 18.3; P less than 0.001). Thus, autoantibodies reactive with the insulin molecule (1) appear to constitute an additional serologic marker of ongoing autoimmunity and development of IDDM, and (2) may reflect heterogeneity in the pathogenesis of IDDM.     

Jogging geht mit niedrigem Absentismus einher (Berner L?uferstudie'84)

Zusammenfassung 4358 männliche Läufer, Teilnehmer am 16-km-Lauf «GP von Bern» 1984, bilden die Studienpopulation einer Querschnittsuntersuchung, in welcher unter anderem die Beziehungen zwischen Jogging und Absentismus analysiert wurden. Die Laufzeit für die 16-km-Strecke und die Zahl der gefehlten Arbeitstage korrelieren positiv (p<0,001); die Laufaktivität (pro Woche im Mittel gelaufene Kilometer) und Absentismus korrelieren entsprechend invers, allerdings nur bis zu einem Trainingsumfang von nicht mehr als ca. 50 km/Woche. Zigarettenrauchende Läufer weisen über 50% mehr Absenzen auf als Nichtrauchende (p<0,001). Zunehmende Bedeutung des Joggingmotivs «als Ausgleich zum Berufsalltag» korreliert invers mit Absentismus (p<0,001), hohe Bedeutung wettkampforientierter Beweggründe für Jogging ist jedoch positiv mit Absentismus assoziiert (p<0,001). Eine multiple Regressionsanalyse mit insgesamt 8 Faktoren vermag lediglich 11% der Varianz der Arbeitsplatzabsenzen zu erklären, was auf die Komplexität der untersuchten abhängigen Variable hindeutet. Die Frage nach der Kausalität der Beziehung zwischen aktivem, regelmässigem (nicht übermässigem) Jogging und erniedrigtem Absentismus bleibt offen. Erst Interventions-studien würden eine bessere Beurteilung des vermuteten Potentials von Bewegung und Sport zur Reduktion von Absentismus erlauben.

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Jogging is related to reduced absenteeism (the Berne Grand-prix study'84)

Summary 4358 male runners over age 16, competitors of the 16 km race Grand-prix of Berne 1984, represent the study population of a cross-sectional survey. As a part of it, relationships between jogging and absenteeism were investigated. 16 km running time was positively associated with the number of missed work days (p<0,001); training activity (kilometers run per week, one-year's average) and absenteeism were related in an inverse way, but only up to a training distance of not more than 50 km/wk. Runners who smoked cigarettes missed over 50% more work days than nonsmokers (p<0,001). The relative importance of the motive for jogging as a balance to work was associated with decreased absenteeism (p<0,001), whereas relative importance of competition-orientated motives was associated with increased absenteeism (p<0,001). A multiple regression analysis involving 8 factors was not able to explain more than 11% of the observed variance in missed work days, which underlines the complexity of this dependent variable. The question concerning a possible causal relationship between active, regular, moderate jogging and reduced absenteeism remains unanswered.

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Le jogging est associé à un absentéisme réduit (Berner Läuferstudie '84)

Résumé 4358 coureurs agés de 16 ans et plus, participants à la course de 16 km «Grand-Prix de Berne» en 1984, forment l'échantillon d'une étude transversale, à l'occasion de laquelle les relations entre le jogging et l'absentéisme ont également été analysées. Il existe une corrélation positive entre le chronométrage des 16 km et le nombre de jours de travail manqués (p<0,001); en plus, la distance parcourue (moyenne des kilomètres de jogging par semaine) et l'absentéisme sont correlés de façon inverse, mais seulement jusqu'à 50 km d'entraînement hebdomadaire. Les coureurs fumeurs de cigarettes ont plus de 50% d'absences de plus que les coureurs non-fumeurs (p<0,001). L'importance relative du motif pour le jogging «comme compensation au travail journalier» est associée de manière inverse à l'absentéisme (p<0,001), tandis que le contraire est le cas pour l'importance des motifs axés vers la compétition (p<0,001). Une analyse multivariée basée sur un total de 8 facteurs peut expliquer que 11% de la variance de l'absentisme, soulignant ainsi le caractère complexe de la variable dépendente analysée. La question visant la relation causale entre le jogging actif et régulier (mais non exagéré) et un absentisme diminué reste ouverte. Seule des études avec intervention permetteraient de mieux juger le potentiel supposé du sport et de l'activité physique en loisir de réduire l'absentisme.

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Der Autor dankt René Rehmann für die Durchführung sämtlicher Datenanalysen, Horst Noack für die kritische Durchsicht des Manuskripts sowie Theres Bietenholz und Christine Vauclair-Liniger für die sekretarielle Hilfe.     

A comparative study of portal vein embolization versus radiation lobectomy with Yttrium-90 micropheres in preparation for liver resection for initially unresectable hepatocellular carcinoma

BackgroundPortal vein embolization before liver resection is considered the therapy of choice for patients with inadequate future liver remnants. The concept of radioembolization with Yttrium-90 to achieve the same goal has limited data.MethodsWe retrospectively compared patients who underwent portal vein embolization and Yttrium-90 lobectomy before resection of hepatocellular carcinoma in patients with chronic liver disease.ResultsSeventy-three patients underwent portal vein embolization and 22 patients underwent Yttrium-90. Forty-seven percent of patients before portal vein embolization required additional procedures for tumor control, and 27% of patients after Yttrium-90 required additional procedure to mainly induce further hypertrophy. Both therapies achieved the goal of future liver remnants >40%, but the degree of hypertrophy was significantly higher in Yttrium-90 patients (63% for Yttrium-90, 36% for portal vein embolization, P < .01). Tumor response was significantly better with Yttrium-90, achieving complete response in 50% of patients. Resectability rate was higher after portal vein embolization (85% for portal vein embolization, 64% for Yttrium-90, P = .03). Tumor progression was the most common reason precluding surgery. Complete tumor control was the reason not to pursue surgery in 18% of patients after Yttrium-90.ConclusionBoth preoperative portal vein embolization and Yttrium-90, increases liver resectability rates by inducing hypertrophy of future liver remnants in patients with hepatocellular carcinoma and chronic liver disease. Yttrium-90 lobectomy achieved better tumor control and provided more time to assess therapy response, optimizing the indication for surgery.     

Racial Disparities in Eligibility for Preemptive Waitlisting for Kidney Transplantation and Modification of eGFR Thresholds to Equalize Waitlist Time

BackgroundPatients may accrue wait time for kidney transplantation when their eGFR is ≤20 ml/min. However, Black patients have faster progression of their kidney disease compared with White patients, which may lead to disparities in accruable time on the kidney transplant waitlist before dialysis initiation.MethodsWe compared differences in accruable wait time and transplant preparation by CKD-EPI estimating equations in Chronic Renal Insufficiency Cohort participants, on the basis of estimates of kidney function by creatinine (eGFR_cr), cystatin C (eGFR_cys), or both (eGFR_cr-cys). We used Weibull accelerated failure time models to determine the association between race (non-Hispanic Black or non-Hispanic White) and time to ESKD from an eGFR of ≤20 ml/min per 1.73 m². We then estimated how much higher the eGFR threshold for waitlisting would be required to achieve equity in accruable preemptive wait time for the two groups.ResultsBy eGFR_cr, 444 CRIC participants were eligible for waitlist registration, but the potential time between eGFR ≤20 ml/min per 1.73 m² and ESKD was 32% shorter for Blacks versus Whites. By eGFR_cys, 435 participants were eligible, and Blacks had 35% shorter potential wait time compared with Whites. By the eGFR_cr-cys equation, 461 participants were eligible, and Blacks had a 31% shorter potential wait time than Whites. We estimated that registering Blacks on the waitlist as early as an eGFR of 24–25 ml/min per 1.73 m² might improve racial equity in accruable wait time before ESKD onset.ConclusionsPolicies allowing for waitlist registration at higher GFR levels for Black patients compared with White patients could theoretically attenuate disparities in accruable wait time and improve racial equity in transplant access.     

ASO Author Reflections: A Plea Against Blind Fear of Benign ‘High-Risk’ Lesions of the Breast: Five Recommendations to Minimize Unnecessary Treatment

Annals of Surgical Oncology -     

Lymphokine-activated killer (LAK) cells modulate the effects of IL-2 on a T cell-mediated immune response.

The ability of LAK cells and/or IL-2 to affect the course of an established T cell response was examined in a delayed-type hypersensitivity (DTH) model. IL-2 greatly increased the magnitude of the response at 24 h, while LAK cells alone had no effect. The administration of LAK cells and IL-2 together also had no effect on the magnitude of the DTH response, demonstrating that LAK cells were able to remove the enhancement seen with IL-2 alone. The presence of LAK cells reduced the serum half-life of IL-2 significantly, but not to an extent able to account for the observed loss of IL-2 induced DTH enhancement. IL-2 administration influenced cell phenotypes in the spleen and draining lymph nodes (DLN), as well as increasing splenic weight; the additional presence of LAK cells markedly altered these effects of IL-2 in the spleen (but not the DLN). Taken together, these results suggest that LAK cells interact with activated T-cells within the immune system and modulate their function.     

Hip fracture mortality and morbidity in Switzerland and Japan: A cross-cultural comparison

Summary Based on national mortality data, the frequency of hip fractures in elderly people was compared between Switzerland and Japan. Age-adjusted annual incidence rates per 100 000 population estimated for Swiss persons over 60 years were around 150 and 200 in males and around 450 in females, while for the Japanese they were only 132 in males and 285 in females. Age-adjusted death rates from hip fracture for the Swiss over 60 were 20.0 in males and 28.9 in females, while for the Japanese they were only 1.6 in males and 2.7 in females. The inclination of the age-dependent slope in hip fracture mortality rates was substantially the same in both countries, but there was a lag time of approximately 10 years in Japan. Remarkably, the proportion of deaths due to falls among all accidental deaths was several times greater in both sexes for the Swiss than for the Japanese. This differential might be an important underlying reason for the observed difference between death rates of hip fracture in Switzerland and Japan. Other known behavioral risk factors for hip fracture such as diet, exercise, estrogen use etc. are unlikely to explain the observed difference in hip fracture mortality and morbidity between Switzerland and Japan. However, given the doubts on the reliability and thus comparability of the available data on mortality and morbidity, the present findings should be regarded as preliminary. In conclusion, we believe that the unexplained and large difference in the burden of hip fracture between Switzerland and Japan merits further studies, including new aetiological hypotheses.

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Zusammenfassung Gestützt auf nationale Sterbedaten wird die Häufigkeit von Hüftfrakturen bei Betagten in der Schweiz und Japan verglichen. Alterskorrigierte jährliche Inzidenzraten (bezogen auf 100 000 Einwohner) bezifferten sich bei den Schweizer Personen über 60 Jahren auf ca. 150–200 bei den Männern sowie ca. 450 bei den Frauen, während bei den Japanern die entsprechenden Inzidenzen lediglich 132 bei den Männern und 285 bei den Frauen betrugen. Die alterskorrigierte durch Hüftfrakturen bedinte Mortalität (pro 100000) betrug bei den Schweizern über 60 Jahren 20,0 bei den Männern und 28,9 bei den Frauen, während bei den Japanern die entsprechenden Werte bei 1,6 für Männer und 2,7 für Frauen lagen. Die Gerade, die das Verhältnis zwischen Alter und Hüftfraktur-Mortalität charakterisiert, zeigte in beiden Ländern ungefähr die gleiche Steigung, war in Japan jedoch um ca. 10 Jahre rechtsverschoben. Bemerkenswerterweise war der Anteil sturzbedingter Todesfälle unter allen unfallbedingten Todesfällen bei beiden Geschlechtern in der Schweiz wesentlich höher als in Japan. Dieser Unterschied könnte eine wichtige, zurgrundeliegende Ursache für die Differenz in der Hüftfrakturmortalität zwischen der Schweiz und Japan darstellen. Andere verhaltensabhängige Risikofaktoren für Hüftfraktur wie Ernährung, körperliche Bewegung, Oestrogenzufuhr usw. vermögen die beobachteten Unterschiede in der Mortalität und Morbidität an Hüftfraktur zwischen der Schweiz und Japan kaum zu erklären Angesichts der ungewissen Reliabilität und Vergleichbarkeit der zur Verfügung stehenden Daten müssen die vorliegenden Ergebnisse allerdings mit Vorsicht interpretiert werden. Zusammenfassend glauben wir, dass der grosse und weitgehend unerklärte schweizerisch-japanische Unterschied im Auftreten von Hüftfrakturen weiter abgeklärt werden sollte, unter Einschluss neuer ätiologischer Hypothesen.

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Résumé Basée sur les données de mortalité nationales, la fréquence des fractures de hanche des personnes âgées est comparée entre la Suisse et le Japon. Les taux d'incidence annuels corrigés pour l'effet de l'âge chez les personnes suisses âgées de plus de 60 ans sont d'environ 150–200 chez les hommes (par rapport à 100 000 habitants), ainsi qu'environ 450 chez les femmes, tandis qu'au Japon les incidences correspondantes s'élèvent à 132 chez les hommes et 285 chez les femmes. La mortalité des fractures de hanche, corrigée pour l'effet de l'âge s'élève chez les Suisses âgés de plus de 60 ans à 20,0 (par 100 000) chez les hommes et à 28,9 chez les femmes, alors que chez les Japonais les taux correspondants sont 1,6 chez les hommes et 2,7 chez les femmes. La proportion de décès faisant suite à des chutes parmi l'ensemble des accidents mortels est remarquablement plus élevée en Suisse qu'au Japon, pour les femmes comme pour les hommes. Cette différence pourrait expliquer le taux élvé de décès suite à une fracture de hanche observé en Suisse. D'autres facteurs de risque pour la fracture de hanche liés au style de vie ne sont apparemment pas en mesure d'expliquer les différences de mortalité et de morbidité par fracture de hanche observées entre la Suisse et le Japon. Face aux doutes qui concernent la fiabilité et la comparabilité des données à disposition, ces résultats doivent être interprétés avec prudence. Toutefois, nous pensons que la différence substantielle des taux de fractures de hanche entre Suisse et Japon, qui reste inexpliquée, devrait être examinée plus en détail, également en ce qui concerne de nouvelles hypothèses étiologiques.

     

Increased neuronal damage in apolipoprotein E-deficient mice following global ischaemia

There is accumulating evidence that apolipoprotein E (apoE) plays a role in regulating the response to and outcome following brain injury. The present study compared the histological outcome and recovery following an episode of global ischaemia in apoE-deficient mice and wild-type littermates (12-week-old males, n = 8 per group). Transient global ischaemia was induced for a period of 17 min and the animals were allowed to recover for 72 h. Transient global ischaemia induced selective neuronal degeneration in several brain regions in wild-type mice. There was statistically significant increased ischaemic neuronal damage in apoE-deficient mice compared with wild-type mice in six of the seven regions examined (hippocampal regions CA1, CA3/CA4 and dentate gyrus; thalamus; cortex and caudate nucleus; P < 0.05). The data substantiate a role for apoE in modifying the response of the CNS to acute injury.