Cardiomyopathy: a late complication of hemolytic uremic syndrome

This report describes a child who presented with classic hemolytic uremic syndrome (HUS) and 4 months later developed a life-threatening but reversible cardiomyopathy with global cardiac dysfunction and a left ventricular ejection fraction of 14%. There was no evidence of electrolyte abnormalities, anemia, hypertension, severe fluid overload, or viral infection. Endomyocardial biopsies were consistent with a dilated cardiomyopathy. This paper highlights the importance of considering the diagnosis of associated cardiomyopathy when presenting with late-onset edema following HUS. Received February 12, 1996; received in revised form and accepted August 22, 1996     

Human ovarian-carcinoma cell lines and companion xenografts: a disease-oriented approach to new platinum anticancer drug discovery

Summary A disease-oriented approach to the discovery of novel platinum anticancer drugs has been established through the setting up of parallel human ovarian-carcinoma cell lines and xenografts. The correlation between in vitro and in vivo antitumour activity was determined for four reference platinum agents (cisplatin, carboplatin, iproplatin and tetraplatin) in eight companion lines. Two methods of assessing antitumour effect were used in vitro (tritiated thymidine incorporation and sulforhodamine B staining) and three were applied in vivo [28-day treated/control (T/C) ratio, growth delay and specific growth delay]. In vitro, large differences in cytotoxicity across the cell lines were observed for each drug. This was also reflected in the xenografts for cisplatin and carboplatin and, to a lesser extent, for iproplatin. A correlation analysis of in vitro vs in vivo data revealed a high, statistically significant positive correlation for cisplatin and a strong positive correlation for carboplatin. However, for the two platinum(IV) drugs, the correlation was less good. In particular, tetraplatin was markedly less active in vivo (showing a general lack of activity against all of the tumour lines) than its in vitro potency against the cell lines predieted, resulting in poor correlation coefficients. These human tumour panels may be valuable for the elucidation of both cellular/molecular and corresponding in vivo pharmacological mechanisms of platinum drug resistance. Moreover, the HX/62 and SKOV-3 tumour lines, which exhibit a level of intrinsic resistance to the four reference agents both in vitro and in vivo (and which were derived from patients who had not received prior platinum therapy), represent particularly useful evaluation models for the discovery of novel broad-spectrum platinum drugs.This study was supported by grants to the Institute of Cancer Research from the Cancer Research Campaign and the Medical Research Council, the Johnson Matthey Technology Centre and Bristol Myers Squibb Oncology     

Retinoic acid induced heparin-binding protein expression and localization during gastrulation,neurulation, and organogenesis

Retinoic acid induced heparin-binding protein (RIHB) is a highly basic, soluble polypeptide of the chick embryonic extracellular matrix. We have examined the expression and localization of RIHB during very early embryogenesis by in situ hybridization and immunohistochemistry. RIHB mRNA is very weakly detectable above background in the blastodiscs of unincubated eggs. The expression increases greatly over the first 24 hours of incubation, and is observed throughout the blastodisc in all three of the germ layers following gastrulation. As neurulation occurs, the expression becomes more restricted to certain areas, notably the ectoderm, the neural folds, and especially the notochord. After the neural tube has formed the expression in the tube itself decreases dramatically, whereas the expression in the head ectoderm and the notochord persists. After 72 hours of incubation expression remains relatively high throughout most of the embryo, with higher levels of expression in regions undergoing organogenesis and lower levels in organs which have already differentiated. RIHB protein is also weakly detectable in unincubated eggs as patches of immunoreactive material between the blastodisc and the vitelline. After 6 hours of incubation small regions of basement membrane are immunoreactive. RIHB is detected in this matrix, apparently before even fibronectin. The amount of RIHB protein increases dramatically over the first 24 hours of incubation. It is found in basement membrane separating the epiblast from the hypoblast, then later in that separating the ectoderm from the mesoderm. It is also detected surrounding individual cells, especially of the ectodermal layer. During neurulation RIHB is observed in the basement membrane surrounding the neural fold and the notochord, and in the lamina separating the ectodermal, mesodermal, and endodermal layers. Later in development, RIHB is detected in the basement membrane under the epidermis, throughout the developing limbs, and in the lamina of various developing organs, such as the eye, the pulmonary bud, the intestine, and the mesonephros. These results demonstrate that RIHB is highly expressed during the early embryonic period, by all three germ layers, and is an important and very early component of the embryonic extracellular matrix. Its very broad expression and localization argue for a more general role in development than its demonstrated weak neurotrophic activity. © 1994 Wiley-Liss, Inc.     

Laparoscopic treatment of nonparasitic cysts of the liver with omental transposition flap

Background: Between 1991 and November 1994, 18 patients with large, solitary, nonparasitic liver cysts underwent laparoscopic deroofing; the last 13 of them also received an omental transposition flap in addition. Methods: Using three to four trocars, the cystic contents were first aspirated, and the cyst derooted widely using diathermia. An omental transposition flap was fashioned and stapled into the cyst cavity itself. Results: Postoperative complications included one case of pulmonary atelectasis. Another patient developed a subhepatic bile collection which was aspirated percutaneously. On average, patients were discharged on the 4th (2–14) postoperative day. Follow-up was performed with abdominal ultrasound for 2–43 months (mean 19 months). There were two early cyst recurrences, both in cases without an omental transposition flap (overall recurrence rate, 11%; in patients with omental flap, 0). Conclusions: Deroofing in combination with an omental transposition flap is a safe and effective therapy for symptomatic solitary liver cysts and can be performed using minimal-access surgical techniques. Received: 19 January 1996/Accepted: 26 August 1996     

Chromosomal aberrations in human lymphocytes induced in vitro by very low doses of X-rays.

This paper presents results of a collaborative experiment between six laboratories which examined the yields of unstable chromosomal aberrations in human lymphocytes induced in vitro by X-rays over the dose range 0-300 mGy. The work included data points of nominal doses of 0, 3, 5, 6, 10, 20, 30, 50 and 300 mGy. Cells from 24 donors were examined and a total of about 300,000 metaphases were scored. The work was undertaken to determine the limits of sensitivity of the system taking into account variations in scoring data due to inter-donor sample and inter-laboratory effects. Despite the existence of these effects, aberration yields significantly in excess of control values were seen at doses greater than 20 mGy and these were consistent with a linear extrapolation from higher doses. Below 20 mGy the observed dicentric yields were generally lower than background, but not significantly so. Excess acentric aberrations, on the other hand, and centric rings, were higher than the controls but the increase was usually not significant. It is concluded that the statistical uncertainties are such that below 20 mGy this technique cannot distinguish between a linear or a threshold model.     

Imaging receptors by autoradiography: computer-assisted approaches.

Receptor autoradiography is one of the first fields where 'desktop' computer-assisted image analysis has been applied. Less than 10 years ago, the first image analysis systems were commercially marketed. Improvements on these early systems have been substantial and there are currently a wide variety of systems available for investigators. These systems dramatically reduce the time required for analysis, improve accuracy and increase the willingness to work in these areas. New techniques allowing autoradiography without emulsion will further expand opportunities for image analysis. While great strides have been made, significant affordable improvements are likely in the near future.     

Ethanol and sucrose self-administration components: effects of drinking history.

Results of previous studies have shown that when rats consume higher concentrations of ethanol during initiation both the amount consumed and the pattern of consumption change with the return to a lower concentration. In this study, an across-sessions breakpoint procedure in the sipper-tube model was used to examine the effect that experience with drinking higher concentrations (a concentration manipulation) of both ethanol and sucrose had on appetitive and consummatory behaviors. A follow-up study was then conducted in the ethanol-consuming group with across-session breakpoint and intake examined before, during, and after a 3% sucrose/10% ethanol solution was presented in the sipper tube. As ethanol concentration increased, intake was not changed. Exposure to higher ethanol concentrations had no effect on the amount of 10% ethanol consumed when retested. The exposure tended to increase appetitive behavior (breakpoint), but this effect was not unique to ethanol, as rats self-administering 3% sucrose showed a similar increase. When the combined ethanol-sucrose solution was available, a significant increase in both intake and appetitive responding occurred; however, there was no change from prior intake or breakpoint when 10% ethanol was retested. That the addition of sucrose to the ethanol solution significantly increased appetitive and consummatory behaviors supports the suggestion that the composition of the alcoholic beverage can have a strong influence over the control of self-administration. Because most consumption of ethanol by human beings is in solutions that contain mixers that alter the taste of the solution, this taste factor needs to be considered in the regulation of ethanol drinking.     

Hemobilia: Review of Recent Experience with a Worldwide Problem

Between 1981 and 1985, the reported incidence of hemobilia increased for two major reasons. First, a more sophisticated and better-trained medical community could entertain the diagnosis readily in certain settings and had broader access to diagnostic methods that precisely defined the source of bleeding into the biliary tract. Second, there was wider use of percutaneous techniques of diagnosis and treatment of biliary diseases. Once the diagnosis of hemobilia was made by endoscopic or arteriographic means, physicians and surgeons were quicker to institute proper therapeutic measures. For this reason, the mortality associated with hemobilia decreased compared with that reported earlier. The medical community must be aware that modern treatments are now the most common cause of this problem. Since invasive diagnostic methods are increasingly used by nonsurgeons, it is imperative that these patients are studied in the context of complete consultation with surgeons who can use definitive treatments when required.     

Release of neuropeptides during intracellular stimulation of single identified Aplysia neurons in culture.

An important criterion for classifying a substance as a neurotransmitter is that it is released in an activity-dependent fashion. We have utilized cell culture of individual neurons of Aplysia to demonstrate the release of the neuropeptides SCPA and SCPB (small cardioactive peptides A and B). Neurons B1 and B2 were isolated from the buccal ganglion of Aplysia and maintained in cell culture. The cells grew new processes, which were immunoreactive to antibodies for the neuropeptide SCPB. These processes contained SCPA and SCPB that were detectable by bioassay on snail heart. The cells synthesized the SCPs from radiolabeled precursors and transported the peptides to their neurites. Single cells released SCPs in a calcium-dependent fashion upon intracellular electrical stimulation. Taken together, these results provide critical evidence that SCPs are neurotransmitters. The results also indicate that the cell culture of individual identified neurons can be used to investigate the release of peptides.