Implications and Management of Lobular Carcinoma in situ of the Breast (LCIS)

Abstract: Lobular carcinoma in situ (LCIS) has gone from a rare form of mammary cancer to a marker of increased risk. Treatment options have undergone a corresponding change from ipsilateral mastectomy with axillary node dissection to observation once it became clear that the majority of patients did not progress to invasive cancer. However, recent events suggest a re-evaluation of LCIS management options. It is clear that even meticulous observation may fail to detect invasive cancer before systemic spread has taken place. This fact plus the identification of breast cancer genes have brought a renewed interest in prophylactic mastectomy. At the same time pathologists feel that it is possible to identify microscopic features of LCIS pointing to an increased likelihood of developing invasive cancer. As a result physicians are being asked to better quantitate risks for individual patients. Most patients with LCIS do not need bilateral mastectomies, but we are coming closer to identifying the minority that would be better served by prophylactic surgery.     

Neurobehavioral effects among subjects exposed to high static and gradient magnetic fields from a 1.5 Tesla magnetic resonance imaging system--a case-crossover pilot study.

The interactive use of magnetic resonance imaging (MRI) techniques is increasing in operating theaters. A study was performed on 17 male company volunteers to assess the neurobehavioral effects of exposure to magnetic fields from a 1.5 Tesla MRI system. The subjects' neurobehavioral performances on a neurobehavioral test battery were compared in four 1-hr sessions with and without exposure to magnetic fields, and with and without additional movements. Adverse effects were found for hand coordination (-4%, P < 0.05; Pursuit Aiming II) and near visual contrast sensitivity (-16% and -15%, P < 0.10; Vistech 6000). The results from the remaining tests were inconclusive due to a strong learning effect. No additional effect from gradient fields was detected. The results indicate that working near a 1.5 Tesla MRI system may lead to neurobehavioral effects. Further research is recommended, especially in members of operating teams using interactive MRI systems.     

Langj?hrige Herzinsuffizienz und Eisenmangelan?mie infolge eines Morbus Rendu-Osler-Weber

Ohne Zusammenfassung     

Amitriptyline pharmacokinetics and clinical response: II. Metabolic polymorphism assessed by hydroxylation of debrisoquine and mephenytoin

A subgroup of 16 out of 30 endogenous depressive inpatients (cf. part I), treated for 3 weeks with 150 mg amitriptyline (AT) daily, participated in a pharmacogenetic study: all were phenotyped with debrisoquine and 3 of them with mephenytoin. Four patients were found to be poor metabolizers (PMs) of debrisoquine and one of mephenytoin. Plasma levels of AT + NT (nortriptyline) were highest in the PMs of debrisoquine, but the ratio of hydroxylated metabolites to the parent compounds appeared to be lower in these subjects. From these data, it is speculated that, in the PM of mephenytoin, the demethylation of AT is impaired. In 12 patients, free plasma 10-hydroxy-AT (ATOH) and 10-hydroxy-NT (NTOH) were found to be bound to a similar extent to plasma proteins, but not so firmly as their parent compounds, by a factor of 6 and 4 respectively. While mean total plasma ATOH reached only 15% of the value of AT, total plasma NTOH was as high as NT. ATOH correlated significantly with its parent compound, but NTOH did not correlate with NT. No drug plasma levels/clinical relationship was found in this small group of patients, even when the hydroxylated metabolites were taken into account. Both poor and extensive metabolizers of debrisoquine responded to treatment. The debrisoquine-test appears to be a useful clinical tool for detecting in patients a genetic deficiency in the hydroxylation of AT-type drugs.     

Ergosterol biosynthesis inhibition by the thiocarbamate antifungal agents tolnaftate and tolciclate.

The thiocarbamate antimycotics tolnaftate and tolciclate blocked sterol biosynthesis in fungal cells and cell extracts, with accumulation of squalene. This point of action was confirmed by the direct inhibition of microsomal squalene epoxidase from Candida albicans. There was no inhibition of other steps in ergosterol biosynthesis. In whole Candida cells, ergosterol biosynthesis inhibition was not complete at drug concentrations up to 100 mg/liter, whereas full inhibition occurred in a cell-free test system. Rat liver cell-free cholesterol biosynthesis was much less sensitive to the drugs. The biochemical action of tolnaftate and tolciclate is thus similar to that of the allylamine antimycotics naftifine and terbinafine.     

Influenza B virus reinfection

Four outbreaks of influenza B infection occurred in Houston, Texas in the years 1976-1984. In the Houston Family Study, age-related infection and illness rates in the recent two epidemics resembled those reported previously. A total of 118 persons, including 35 children followed from birth, were followed longitudinally through this entire period and 331 persons were studied through at least two outbreaks. Fifty-nine (88%) of 67 children studied for four outbreaks were infected and 25% had a second infection; about half of the adults had one infection but only one of 51 was reinfected. Infection rates were proportionally lower for those followed through 2-3 outbreaks. Those with documented infection were protected decreasingly over time against reinfection and associated illness in subsequent epidemics. Such protection decreased in efficacy from 65% after 2-3 years, to 46% after 4-5 years, and to no protection after seven years.     

Isolation and interspecies-transfer of a plasmid from Pasteurella multocida encoding for streptomycin resistance

A plasmid encoding streptomycin-resistance could be detected in 13 of 32 Pasteurella multocida-cultures isolated from cattle and swine. The plasmid of these cultures proved to be similar upon Southern blot hybridization. It could be transformed into Escherichia coli 490A, where it also expressed streptomycin resistance.     

The balance of positive and negative affects in major depression: a further test of the States of Mind model.

The States of Mind (SOM) model provided a framework for assessing the balance between self-reported positive and negative affects in a sample of 39 outpatients with major depression and 43 healthy control subjects. The SOM model proposes that healthy functioning is characterized by an optimal balance of positive (P) and negative (N) cognitions or affects (P/(P + N) approximately 0.63), and that psychopathology is marked by deviations from the optimal balance. Research thus far has focused on the functional significance of cognitive rather than affective balance. Within this framework, we hypothesized that patients in untreated episodes of major depression would balance their positive and negative affects at the same level where depressed patients in other studies have balanced their positive and negative cognitions--namely, at P/(P + N) approximately 0.37. Points and confidence interval (CI) estimation procedures yielded results (mean = 0.35, 95% CI = 0.30 - 0.40) consistent with this hypothesis in a sample of 39 depressed male outpatients. Correlational analysis indicated that affect balance is inversely related to symptom severity as measured by self-report (Beck) and clinician-rating (Hamilton) scales.