FRACTALS IN PATHOLOGY

Many natural objects, including most objects studied in pathology, have complex structural characteristics and the complexity of their structures, for example the degree of branching of vessels or the irregularity of a tumour boundary, remains at a constant level over a wide range of magnifications. These structures also have patterns that repeat themselves at different magnifications, a property known as scaling self-similarity. This has important implications for measurement of parameters such as length and area, since Euclidean measurements of these may be invalid. The fractal system of geometry overcomes the limitations of the Euclidean geometry for such objects and measurement of the fractal dimension gives an index of their space-filling properties. The fractal dimension may be measured using image analysis systems and the box-counting, divider (perimeter-stepping) and pixel dilation methods have all been described in the published literature. Fractal analysis has found applications in the detection of coding regions in DNA and measurement of the space-filling properties of tumours, blood vessels and neurones. Fractal concepts have also been usefully incorporated into models of biological processes, including epithelial cell growth, blood vessel growth, periodontal disease and viral infections. © 1997 John Wiley & Sons, Ltd.     

SCHIZOPHRENIA WITH ONSET AT THE EXTREMES OF ADULT LIFE

Objective. To define the epidemiology, phenomenology, premorbid and risk factors in patients with the first manifestation of a schizophrenia-like illness after the age of 60 years, and compare them with patients with an onset before the age of 25 years. Design/setting/subjects. All contacts for a non-affective psychotic illness across all ages of onset were ascertained through a psychiatric case register; patients were rediagnosed according to operationalized criteria for psychotic illness, and those with a very early and very late onset compared. Main outcomes measures. Phenomenological, premorbid and aetiological parameters were compared in the two groups, using risk ratios and 95% confidence intervals. Results. Very late onset patients (N=72) were, compared to their very early onset counterparts (N=192), more likely to be female, have good premorbid functioning and developmental history, and to exhibit persecutory delusions and hallucinations; they were less likely to have negative schizophrenic symptoms, to have a positive family history of schizophrenia, or have suffered pregnancy or birth complications. Conclusions. The results highlight premorbid, aetiological and phenomenological differences between patients with the onset of a schizophrenia-like illness at the extremes of adult life, and suggest it is premature to consider the two groups to be merely different manifestations of the same illness. © 1997 John Wiley & Sons, Ltd.     

EVALUATING TREATMENTS WHEN A GENDER BY TREATMENT INTERACTION MAY EXIST

We propose a two-stage procedure for investigating whether males and females respond differently to treatment. The size of the first stage is based on the assumption of homogeneity of treatment effects across genders. Using stage I, we test for a gender by treatment interaction. If non-significant, we compute an overall average treatment effect and terminate the study. If we find an apparent interaction at the end of the first stage, we consider each gender separately. Because we now need to estimate treatment effects separately for each gender, we may have a need to collect additional information in a second stage. We consider the performance of our procedure for a normally distributed endpoint as well as for a survival model. © 1997 by John Wiley & Sons, Ltd.     

Allergic skin reactions provoked by a root canal disinfectant with reduced formaldehyde concentration

Abstract. The immunogenic potential of a root canal disinfectant (FA 6/25) with a reduced formaldehyde concentration (one-third of that in Formocresol) was studied after application to one incisor tooth per guinea-pig, both presensitized and non-presensitized. Skin reaction after occlusive patch testing was studied. Several indications were found that the disinfectant caused an allergic reaction.     

Do Traditional VT Zones Improve Outcome in Primary Prevention ICD Patients?

Aims: We reviewed outcomes in our primary prevention implantable cardioverter defibrillator (ICD) population according to whether the device was programmed with a single ventricular fibrillation (VF) zone or with two zones including a ventricular tachycardia (VT) zone in addition to a VF zone. Methods: This retrospective study examined 137 patients with primary prevention ICDs implanted at our institution between 2004 and 2006. Device programming and events during follow‐up were reviewed. Outcomes included all‐cause mortality, time to first shock, and incidence of shocks. Results: Eighty‐seven ICDs were programmed with a single VF zone (mean >193 ± 1 beats per minute [bpm]) comprising shocks only. Fifty ICDs had two zones (mean VT zone >171 ± 2 bpm; VF zone >205 ± 2 bpm), comprising antitachycardia pacing (100%), shocks (96%), and supraventricular (SVT) discriminators (98%) . Discriminator “time out” functions were disabled. Mean follow‐up was 30 ± 0.5 months and similar in both groups. All‐cause mortality (12.6% and 12.0%) and time to first shock were similar. However, the two‐zone group received more shocks (32.0% vs 13.8% P = 0.01). Five of 16 shocks in these patients were inappropriate for SVT rhythms. The single‐zone group had no inappropriate shocks for SVTs. Eighteen of 21 appropriate shocks were for ventricular arrhythmias at rates >200 bpm (three VF, 15 VT). This suggests that primary prevention ICD patients infrequently suffer ventricular arrhythmias at rates <200 bpm and that ATP may play a role in terminating rapid VTs. Conclusions: Patients with two‐zone devices received more shocks without any mortality benefit. (PACE 2010; 1353–1358)     

Effects of Coumarin Following Perinatal and Chronic Exposure in Sprague-Dawley Rats and CD-1 Mice

Coumarin, a naturally occurring substance most frequently usedas a fragrance enhancer and stabilizer, was administered inthe diet of Sprague-Dawley rats at dose levels of 0, 333, 1000,2000, 3000, and 5000 ppm or in the diet of CD-1 mice at doselevels of 0, 300, 1000, or 3000 ppm. Rats receiving 333, 1000,and 2000 ppm coumarin were exposed to these dose levels in uteroand during the lactational period, then chronically followingweaning. Rats in the 3000- and 5000-ppm dose groups and allmice received only postweanlng chronic exposure. All male ratswere terminated after 104 weeks of postweaning exposure; femalerats were terminated after 110 weeks. Male mice were terminatedat Week 101 and female mice at Week 109. Among rats, survivalwas decreased at 333 ppm, but signilicantly increased amongrats in the 3000- and 5000-ppm dose groups. Dramatic dose-relateddecreases in body weight gain were recorded for rats receiving2000, 3000, and 5000 ppm, clearly indicating that the MTD (maximumtolerated dose, as indicated by a body weight decrement of greaterthan 10–15%) was exceeded. Food consumption also was decreasedat the three highest dose levels, although body weight decrementwas disproportionately large compared to changes in food consumption.Treatment-related decreases in hemoglobin were recorded fromWeek 6 onward. Minimal treatment-related changes in he matologyand clinical chemistry were recorded. Increased liver weightswere observed for male and female rats receiving 3000 or 5000ppm and for females only at 1000 and 2000 ppm. Increased incidencesof cholanglofibroma, cholangiocarcinoma, and parenchymal livercell tumors were observed among male and female rats receiving5000 ppm. One male rat receiving 3000 ppm devel oped a cholangiocarcinoma;no tumor increase was observed in males or females at 2000 ppmor below. Coumarin, at a dose clearly exceeding the MTD can,therefore, induce liver tumors in rats, although survival, relativeto controls, was increased at the same dose levels. Among mice,a decrease in body weight gain was reported for males in the1000- and 3000-ppm dose groups during the first 52 weeks ofthe study. No dose-related abnormalities in clinical signs,clinical pathology, hematology, or gross or microscopic pathologywere noted.     

Enhanced association of plasminogen/plasmin with lesional epidermis of bullous pemphigoid

The distribution of plasminogen/plasmin, the central proteolytic component of the plasminogen activator/plasmin system was analysed in lesional skin of bullous pemphigoid by using monoclonal antibodies (MAbs) specific for distinct epitopes of the plasminogen/plasmin molecule. Four groups of MAbs were used: (i) MAbs HD-PG 1 and HD-PG 2, specific for epitopes associated with the lysine-binding sites I (kringle domain 1 + 2 + 3) and II (kringle domain 4) of plasminogen/plasmin, (ii) MAbs HD-PG 6 and HD-PG 7, specific for the lysine binding site I only, (iii) MAbs HD-PG 12 (formerly designated P 2) and HD-PG 18, specific for non-kringle domains of glu- and lys-plasminogen, and (iv) MAb HD-PG 13 which recognizes glu-plasminogen, only. The basal cell layers of normal skin consistently reacted with MAb HD-PG 12, whereas only faint staining was seen with the other MAbs in the same biopsies. In contrast, all anti-plasminogen/plasmin MAbs strongly stained lower and intermediate epidermal cell layers of fully developed bullous pemphigoid lesions.