Patient preferences on the use of technology in cancer surveillance after curative surgery: A cross-sectional analysis

Background

Advances in communication technology have enabled new methods of delivering test results to cancer survivors. We sought to determine patient preferences regarding the use of newer technology in delivering test results during cancer surveillance.

Mittheilung einiger Fälle von Meningea-Blutungen,nebst Bemerkungen über die Technik der Eröffnung des Schädels bei denselben

Ohne Zusammenfassung (Mit 2 Abbildungen.)     

Experimentelle Untersuchungen zum Einfluß der Ovarialhormone auf die Entwicklung der Rattenmandibula

Zusammenfassung Weiblichen Ratten des Wistar-Stammes wurden am 1. oder 2. Lebenstag die Ovarien entfernt. Intakte Wurfgeschwister dienten als Kontrolltiere. An den mazerierten Unterkiefern erfolgten Flächen- sowie Längen- und Streckenmessungen von der Geburt an bis zur Pubertät. Es zeigte sich, daß insgesamt die Wachstumsraten bei den neonatal ovarektomierten Tieren im Vergleich zur Kontrollgruppe geringer waren. Deutliche Unterschiede wurden vor allem an den Mandibularflächen und im Vertikaldurchmesser des Kondylarbereiches gefunden. Der Flächeninhalt der Mandibulae stieg im Untersuchungszeitraum auf das 6fache, die Fläche im Bereich der Kondylen vergrößerte sich im gleichen Zeitraum auf das 14fache. Aus den Ergebnissen kann gefolgert werden, daß das Wachstum der Mandibula durch die niedrige präpubertale Sekretion der Ovarialhormone stimuliert wird. Den stärkeren Einfluß üben aber wahrscheinlich andere Wuchsfaktoren, z. B. Wachstumshormon, Schilddrüsenhormone, Androgene und wahrscheinlich das Insulin aus.

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Summary Female rats of a Wistar strain were ovariectomized on the first day of life. Intact littermates served as controls. The growth of the mandibles was evaluated from birth till puberty by measuring the total area as well as the length and the distance between different points. The results demonstrated a generally lower mandibular growth in the neonatally castrated females as compared to the intact controls. Significant differences were mainly found in the total area of the mandible as well as in the vertical diameter of the condyles. Throughout the period of investigation, the total area of the mandibles increased 6fold and that of the condyles 14fold. The findings suggest that the relatively low oestrogen secretion during the prepubertal development stimulates mandibular growth, but that the predominant influence may be exerted by other growth factors, e. g. growth hormone, thyroid hormones, androgens and probably insulin.

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Résumé Des rates de la colonie Wistar furent ovariectomisées un ou deux jours après la naissance. Des soeurs intactes servirent de contrôle. Depuis la naissance jusqu'à la puberté, on mesura la croissance des mandibules, tant sur leur surface totale que sur leur longueur et on nota la distance séparant différents points donnés. Les résultats ont montré une croissance mandibulaire généralement inférieure chez les femelles châtrées, dans la période néonatale, par rapport aux femelles intactes du groupe de contrôle. On observa des différences significatives dans la surface mandibulaire, ainsi que dans le diamètre vertical de la région condylienne. La surface totale des mandibules augmenta de 6 fois et celle des condyles de 14 fois pendant la période d'observation. On pourrait conclure, au vu des résultats obtenus, que la croissance mandibulaire est stimulée par la sécrétion prépubérale relativement basse d'oestrogènes, mais que l'influence prédominante appartient probablement à d'autres facteurs de croissance, tels que l'hormone de croissance, les hormones thyroidiennes, les androgènes et probablement l'insuline.

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Herrn OMR Prof. Dr. med. habil.R. Fränkel zum 75. Geburtstag, vorgetragen beim Geburtstagssymposium in Reinhardsbrunn.     

PM–Scl‐75 is the main autoantigen in patients with the polymyositis/scleroderma overlap syndrome

Objective

To compare the autoantigenicity of the recently described N‐terminally elongated PM–Scl‐75 protein with that of PM–Scl‐100 and the originally defined PM–Scl‐75 polypeptide, and to determine its value for analyzing sera from patients with the polymyositis (PM)/scleroderma overlap syndrome.

Methods

Serum samples obtained from patients with the PM/scleroderma overlap syndrome and from patients with several other diseases were analyzed for the presence of autoantibodies reactive with recombinant PM–Scl‐100 and PM–Scl‐75 (both the original and the longer form) proteins, in an enzyme‐linked immunosorbent assay (ELISA).

Results

Autoantibodies recognizing the longer PM–Scl‐75 protein isoform were detected in 28% of the patients with PM/scleroderma. This percentage is slightly higher than that for PM–Scl‐100 (25%) and is significantly higher than that for the previously defined PM–Scl‐75 protein (11%). In addition, we identified a significant number of patients who had anti–PM–Scl‐75 but not anti–PM–Scl‐100 antibodies. This finding contrasts with what has been previously reported for the shorter version of the PM–Scl‐75 protein.

Conclusion

Our data indicate that use of the long PM–Scl‐75 isoform in addition to PM–Scl‐100 in ELISAs significantly increases the number of patients in whom anti–PM‐Scl autoantibodies can be detected.

     

Dyskerin localizes to the nucleolus and its mislocalization is unlikely to play a role in the pathogenesis of dyskeratosis congenita.

Mutations in the DKC1 gene are responsible for causing the bone marrow failure syndrome, dyskeratosis congenita (DKC; OMIM 305000). The majority of mutations identified to date are missense mutations and are clustered in exons 3, 4 and 11. It is predicted that the corresponding protein dyskerin is a nucleolar phosphoprotein which functions in both pseudo-uridylation and cleavage of precursor rRNA. Dyskerin contains multiple putative nuclear localization signals (NLSs) at the N-terminus (KKHKKKKERKS) and C-terminus [KRKR(X)(17)KKEKKKSKKDKKAK(X)(17)-KKKKKKKKAKEVELVSE]. By fusing dyskerin with the enhanced green fluorescent protein (EGFP) and by following a time course of expression in mammalian cell lines, we showed that full-length dyskerin initially localizes to the nucleoplasm and subsequently accumulates in the nucleoli. A co-localization to the coiled bodies was observed in some cells where dyskerin-EGFP had translocated to the nucleoli. Analysis of a series of mutant constructs indicated that whereas the most C-terminal lysine-rich clusters [KKEKKKS-KKDKKAK(X)(17)KKKKKKKKAKEVELVSE] influence the rate of nucleoplasmic and nucleolar accumulation, the KRKR sequence is primarily responsible for the nuclear import. Nucleolar localization was maintained when either the N- or C-terminal motifs were mutated, but not when all NLSs were removed. We conclude that the intranuclear localization of dyskerin is accomplished by the synergistic effect of a number of NLSs and that the nucleolar localization signals are contained within the NLSs. Further, examination of dyskerin-EGFP fusions mimicking mutations detected in patients indicated that the intracellular mislocalization of dyskerin is unlikely to cause DKC.     

Immediate recall of oral contraceptive instructions: Implications for providers

Objective: The object of the study was to determine the patient characteristics associated with inadequate recall of oral contraceptive pill-taking instructions. Study Design: Sexually active women aged 13 to 40 years (n = 150) attending university-based family planning clinics completed anonymous self-report measures that assessed demographic and reproductive characteristics, understanding of pill-taking instructions, and contraceptive compliance. Logistic regression was used to determine factors associated with inadequate recall for the sample, stratified by minority versus nonminority women. Results: Minority women with inadequate recall were almost 6 times more likely than minority women with adequate recall not to know the name of the prescribed oral contraceptive and were 3 times more likely to have less than a high school education. In addition there were 1-fold and 2-fold increases in likelihood of inadequate recall as certainty of pill-taking instructions and general oral contraceptive knowledge, respectively, decreased. Inadequate recall was associated with poor compliance. Conclusion: Women with inadequate recall may be identified at the conclusion of their visit so that interventions to enhance their pill-taking skills can be provided. (Am J Obstet Gynecol 1999;180:1399-406.)     

Selective inhibition of the Na+/H+ exchanger type 3 activates CO2/H+-sensitive medullary neurones

Hypercapnia as well as lowered intracellular pH (pH_i) increase the bioelectric activity of CO₂/H⁺-sensitive neurones (VLNcs) of the ventrolateral medulla oblongata. Here we describe that immunoreactive Na⁺/H⁺ exchanger (NHE3) is present in ventrolateral neurones from medullary organotypic cultures (obex level). To test whether VLNcs can be acidified and thereby activated by inhibition of NHE3, we used the novel high-affinity NHE3-inhibitors S1611 and S3226. Both drugs raised the firing rates of VLNcs to at least 150% of the control values, and depolarized membrane potential by up to 15 mV at concentrations (0.5–1 μmol/l) suitable for selective inhibition of NHE3. The changes in bioelectric activity strongly resembled the responses to hypercapnia (PCO₂: 60–100 mmHg). In BCECF-AM-loaded cultures a subfraction of ventrolateral VLNcs was found to be intracellularly acidified by 0.05–0.1 pH units following treatment with S1611; the time course of this acidification was similar to that evoked by hypercapnia. All drug effects were sustained and readily reversible upon washing. Non-CO₂/H⁺-responsive medullary neurones as well as hippocampal CA3 neurones were unaffected by up to 20 μmol/l S1611. It is concluded that the selective inhibition of NHE3 acidifies and activates CO₂/H⁺-sensitive neurones within the ventrolateral medulla oblongata. Received: 12 February 1999 / Received after revision and accepted: 15 April 1999     

Anti-inflammatory effects of the anticonvulsant drug levetiracetam on electrophysiological properties of astroglia are mediated via TGFβ1 regulation

BACKGROUND AND PURPOSE

The involvement of astrocytes as immune-competent players in inflammation and the pathogenesis of epilepsy and seizure-induced brain damage has recently been recognized. In clinical trials and practice, levetiracetam (LEV) has proven to be an effective antiepileptic drug (AED) in various forms of epileptic seizures, when applied as mono- or added therapy. Little is known about the mechanism(s) of action of LEV. Evidence so far suggests a mode of action different from that of classical AEDs. We have shown that LEV restored functional gap junction coupling and basic membrane properties in an astrocytic inflammatory model in vitro.

EXPERIMENTAL APPROACH

Here, we used neonatal rat astrocytes co-cultured with high proportions (30%) of activated microglia or treated with the pro-inflammatory cytokine interleukin-1β to provoke inflammatory responses. Effects of LEV (50 µg·mL⁻¹) on electrophysiological properties of astrocytes (by whole cell patch clamp) and on secretion of TGFβ1 (by elisa) were studied in these co-cultures.

KEY RESULTS

LEV restored impaired astrocyte membrane resting potentials via modification of inward and outward rectifier currents, and promoted TGFβ1 expression in inflammatory and control co-cultures. Furthermore, LEV and TGFβ1 exhibited similar facilitating effects on the generation of astrocyte voltage-gated currents in inflammatory co-cultures and the effects of LEV were prevented by antibody to TGFβ1.

CONCLUSIONS AND IMPLICATIONS

Our data suggest that LEV is likely to reduce the harmful spread of excitation elicited by seizure events within the astro-glial functional syncytium, with stabilizing consequences for neuronal–glial interactions.     

Genetic association of the human corticotropin releasing hormone receptor 1 (CRHR1) with binge drinking and alcohol intake patterns in two independent samples

To investigate the role of the corticotropin releasing hormone receptor 1 (CRHR1) in patterns of human alcohol drinking and its potential contribution to alcohol dependence, we analysed two independent samples: a sample of adolescents, which consisted of individuals from the 'Mannheim Study of Risk Children' (MARC), who had little previous exposure to alcohol, and a sample of alcohol-dependent adults, who met DSM-IV criteria of alcohol dependence. Following determination of allelic frequencies of 14 polymorphisms of the CRHR1 gene, two haplotype tagging (ht)SNPs discriminating between haplotypes with a frequency of > or =0.7% were identified. Both samples were genotyped and systematically examined for association with the htSNPs of CRHR1. In the adolescent sample, significant group differences between genotypes were observed in binge drinking, lifetime prevalence of alcohol intake and lifetime prevalence of drunkenness. The sample of adult alcohol-dependent patients showed association of CRHR1 with high amount of drinking. This is the first time that an association of CRHR1 with specific patterns of alcohol consumption has been reported. Our findings support results from animal models, suggesting an importance of CRHR1 in integrating gene-environment effects in alcohol use disorders.