Stricture and perforation of the esophagus: Overlooked threats in the Zollinger-Ellison syndrome

This study was undertaken to assess the frequency of significant esophageal involvement in the Zollinger-Ellison syndrome (ZES). In a consecutive series of 24 patients with this disease, 9 (37%) showed endoscopic evidence of acid-induced esophageal lesions ranging from erosive inflammation to ulceration with massive bleeding, severe stricture formation, and perforation. In 3 cases, pronounced esophagitis was known 1–5 years before the underlying disease was diagnosed. Severe esophageal complications developed despite treatment with antisecretory drugs. It is emphasized that the best way to limit such complications is by excision of the underlying gastrin-secreting tumor(s) when possible.

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Resumen El presente estudio fue emprendido con el propósito de determinar la frecuencia de afección ácido péptica significativa del esófago en pacientes con síndrome de Zollinger-Ellison. En una serie de 24 pacientes consecutivos con esta enfermedad, 9 (37%) exhibieron evidencia endoscópica de lesiones esofágicas inducidas por ácido, las cuales variaron entre inflamación erosiva y ulceración con sangrado masivo, estrechez severa, y perforación. En 3 pacientes se conocía la existencia de esofagitis severa entre 1 y 5 años antes del diagnóstico de la enfermedad de base. Se desarrollaron graves complicaciones esofágicas a pesar del tratamiento con drogas antisecretorias en 3 pacientes. Se hace enfasis en que la mejor manera de disminuir tales complicaciones es mediante la resección del tumor(es) secretor de gastrina, cuando ello sea posible.

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Résumé Nous avons entrepris cette étude pour établir la fréquence de participation oesophagienne dans le syndrome de Zollinger-Ellison. Pour une série de 24 patients présentant cette maladie, 9 (37%) avaient à l'endoscopie des lésions oesophagiennes dues à l'acidité allant de l'érosion inflammatoire à l'ulcération avec saignement important, sténose sévère, et perforation. Dans 3 cas, une oesophagite importante était connue 1–5 ans avant que la maladie sous-jacente soit diagnostiquée. Des complications oesophagiennes sévères se sont produites malgré le traitement antisécrétoire. Nous insistons sur le fait que le meilleur moyen de limiter ces complications est d'exciser chaque fois que possible la ou les tumeurs sous-jacentes sécrétant la gastrine.

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Presented at the International Association of Endocrine Surgeons in Toronto, Ontario, Canada, September, 1989.

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Supported by grants from the Swedish Medical Research Council, the Swedish Society of Medicine, the Anders Otto Swärd Foundation, and the Surgery Foundation of Skövde Central Hospital.     

Cardiovascular collapse during anesthesia in a patient with preoperatively discontinued chronic MAO inhibitor therapy

We describe a patient in whom long-term monoamine oxidase (MAO) inhibitor therapy was discontinued 20 days before surgery with general anesthesia. This patient developed severe perioperative hypotension after administration of 10 mg of bupivacaine through an epidural catheter, which was corrected only after potent vasopressor therapy. We attribute this hemodynamic instability to attenuation of this patient's sympathetic tone based on several mechanisms: (1) residual effect of long-term administration of MAO inhibitor that caused a decrease in the number of β-adrenergic receptors (adrenergic subsensitivity due to receptor down-regulation), (2) recovered MAO activity causing effective degradation of sympathetic amines, and (3) combined attenuating effects of general and epidural anesthesia on sympathetic tone.     

System for prostate brachytherapy and biopsy in a standard 1.5 T MRI scanner.

A technique for transperineal high-dose-rate (HDR) prostate brachytherapy and needle biopsy in a standard 1.5 T MRI scanner is demonstrated. In each of eight procedures (in four patients with intermediate to high risk localized prostate cancer), four MRI-guided transperineal prostate biopsies were obtained followed by placement of 14-15 hollow transperineal catheters for HDR brachytherapy. Mean needle-placement accuracy was 2.1 mm, 95% of needle-placement errors were less than 4.0 mm, and the maximum needle-placement error was 4.4 mm. In addition to guiding the placement of biopsy needles and brachytherapy catheters, MR images were also used for brachytherapy treatment planning and optimization. Because 1.5 T MR images are directly acquired during the interventional procedure, dependence on deformable registration is reduced and online image quality is maximized.     

RBE and w(R) values of Auger emitters and low-range beta emitters with particular reference to tritium.

An apparent disparity exists between RBE (relative biological effectiveness) values for low-range beta and Auger emitters, and the current value for their radiation weighting factor (w(R)). This paper presents evidence that the current w(R) value of unity for these nuclides is inconsistent with most RBE evidence and should be increased by a factor of two to three. It recommends that the ICRP should clearly state that the most appropriate RBE value for these nuclides, and not the w(R) value, should be used in specific dose calculations, retrospective dose estimations and epidemiological studies. The ICRP should also publish guidance as to the methods and data sources that could be used for these RBE values.     

Stress-Related Changes in β-Endorphin Processing: The Limitations of Slaughterhouse Material

In the sheep, unlike many other species, a significant proportion (>25%) of immunoreactive β-endorphin in the anterior pituitary is post-translationally modified to opioid-inactive, α-N-acetylated forms. In a study to determine the precise molecular nature of α-N-acetylated β-endorphin immunoreactivity, we noted a striking difference in high-performance liquid chromatography profiles of anterior pituitary extracts between sheep killed on the farm, and age-, sex- and strain-matched slaughterhouse animals. These altered patterns of a-N-acetylated β-endorphin processing were reproduced in farm animals by chronic (≤ 4 days) treatment with the synthetic glucocorticoid dexamethasone; in contrast dexamethasone had no effect on a-N-acetylated β-endorphin processing in hypothalamo-pituitary disconnected sheep. These data suggest that (1) the change in processing is a stress response, mediated by prolonged glucocorticoid exposure, (2) this effect is central, rather than a direct effect on the pituitary, and (3) the relative abundance of various peptide sequences in slaughterhouse-derived material may not reflect their abundance under more physiological conditions.     

Transluminal angioplasty of the vertebral and basilar artery

Transluminal angioplasty of brachiocephalic vessels for atherosclerotic lesions is now being performed in selected cases. We have thus far treated 17 cases of vertebral artery stenosis and one case of basilar artery stenosis by intravascular balloon dilatation techniques. Clinical presenting symptoms included vertebral basilar insufficiency, repeated transient ischemic attacks (TIAs), and multiple strokes. We performed successful transluminal angioplasty in 16 patients with marked narrowing (greater than 70%) of the dominant vertebral artery from atherosclerosis. One patient with basilar artery stenosis with tandem atherosclerotic lesions was also treated by angioplasty techniques. Repeat angiography at 3- to 12-month intervals has revealed continued patency at the angioplasty site. Complications occurred in our one patient with basilar artery angioplasty, who suffered a brainstem infarction after treatment, and in one patient who had a TIA after bilateral vertebral artery angioplasty. Two other patients had residual vertebral stenosis but remained asymptomatic after the procedure. All other patients who had successful dilatation were asymptomatic at 6 months to 2 years (mean, 15 months) of follow-up. These initial studies indicate that vertebral artery angioplasty may be effective for treating high-grade atherosclerotic lesions and for improving blood flow to the posterior circulation. Angioplasty of the basilar artery is technically more difficult and has a higher degree of risk because of the many perforating branches supplying the brainstem.     

A mathematical model of volatile release in mouth from the dispersion of gelled emulsion particles.

This paper presents a mathematical model of in-mouth volatile release from gelled emulsion particles dispersed in a continuous aqueous phase. Data based on APCI MS-Breath analysis is presented to demonstrate the effect of particle size, oil content and oil-water partition coefficients. It is shown that in-mouth release of aroma from the dispersion of gelled emulsion particles follows a two-component kinetic equation with fast and slow components. Both the fast and slow rate constants depend on the particle size, oil content and oil water partition coefficient of the aroma. The relative amount of aroma contributing to the fast and slow components also depends on the size of the particles. In order to understand this unexpected behaviour, an analytical model was developed that considers the interplay between the mass transfer of flavour across the interface of the particles and that across the air-liquid interface. Analytical expressions for the two rate constants and the relative ratio of aroma contributing to the fast component have been derived. From this model, three regimes of in-mouth release of aroma from the dispersion of gelled emulsion particles were identified including, the emulsion regime, the transition regime and the gel particle regime. In the emulsion regime, changes in the size of gelled emulsion particles had negligible impact on the overall release. In the transition regime, the release was controlled by the interaction of flavour transfer from the particles with that across the air-water interface. In the gel particle regime, aroma release at long times was governed by the particles and that at short times was governed by the air-water interface, and the two processes were fully decoupled. A simple relationship was derived for the critical size above which the release of aroma from the dispersion of gelled emulsion particles is affected by the size of the particles.     

Heart rate and blood pressure variability as markers of sensory blockade with labour epidural analgesia

PURPOSE: To evaluate the correlation between the progression of somatosensory blockade and changes in autonomic outflow following the onset of labour epidural analgesia. METHODS: Twelve labouring parturients consented to participate in the study. Baseline electrocardiogram, blood pressure (BP) and respiratory rate were recorded for ten minutes. The epidural consisted of 0.125% bupivacaine with 50 microg of fentanyl (total volume 20 mL). Measurements were repeated for ten minutes after initiation of the block. The level of sensory block was measured bilaterally with loss of sensation to ice at two-minute intervals. Wavelet transform was used to obtain heart rate (HR) and BP variability every two minutes following the loading dose of epidural medication. High frequency power of HR variability was used to assess changes in parasympathetic activity. The total power of BP variability was used to assess changes in sympathetic activity. A nonparametric repeated measures ANOVA was used for the variability data, and a Spearman rank correlation test was used to evaluate the relationship between the sensory block and HR and BP variability. RESULTS: The sensory block progressed to T9 at ten minutes post-epidural and was the mirror image of the decrease in total power of BP variability. High frequency power of HR variability increased to a plateau at six minutes post-epidural. A significant correlation was found between the increase in sensory block and the observed decrease in BP variability (r = -1.000, P = 0.0028). CONCLUSION: In this study of labouring parturients, BP variability correlated with the progression of both sympathetic and somatosensory block following epidural anesthesia, while HR variability was shown to be a surrogate marker of increased parasympathetic activity.     

Differential gene expression in cultured osteoblasts and bone marrow stromal cells from patients with Paget's disease of bone.

Paget's disease is a focal condition of bone. To study changes in cells within pagetic lesions, we cultured osteoblasts and stromal cells from 22 patients and compared gene expression in these cells to cells from healthy bone. We identified several differentially regulated genes, and we suggest that these changes could lead to the formation of the lesions. INTRODUCTION: Paget's disease is a focal condition of bone of unknown cause. Although it is regarded as primarily an osteoclast disorder, the tight coupling of the activity of osteoclasts and osteoblasts suggests that the osteoblast could play a key role in its pathogenesis. The aim of the study was to identify possible changes in pagetic osteoblasts and stromal cells that might contribute to the development of pagetic lesions. MATERIALS AND METHODS: Candidate genes were identified based on known bone cell regulators, supplemented with microarray analysis. Gene expression was determined by real-time PCR in primary cultures of osteoblasts and bone marrow stromal cells from pagetic patients and control subjects. Concentrations of secreted proteins were determined by ELISA. RESULTS: Dickkopf1 mRNA and protein levels were increased in both pagetic osteoblast and stromal cell cultures, and interleukin (IL)-1 and IL-6 were overexpressed in pagetic osteoblasts. These changes parallel recent findings in myeloma bone disease, which shares some clinical similarities with Paget's disease. Alkaline phosphatase was overexpressed, and bone sialoprotein and osteocalcin were underexpressed in pagetic osteoblasts, consistent with their circulating levels in pagetic patients. It is hypothesized that overexpression of Dickkopf1, IL-1, and IL-6 would result in stimulation of osteoclast proliferation and inhibition of osteoblast growth, leading to the development of the characteristic lytic bone lesions. By stimulating osteoblast differentiation, Dickkopf1 and IL-6 may also promote mineralization, leading to the conversion of lytic lesions to sclerotic. CONCLUSIONS: These findings suggest that dysregulated gene expression in pagetic osteoblasts could cause the changes in bone cell number and function characteristic of Paget's disease.