Penicillamine-Induced Degenerative Dermatoses: Report of a Case and Brief Review of Such Dermatoses

We describe a case of elastosis perforans serpiginosa with additional findings of degenerative skin changes. A 20-year-old man with hepatolenticular degeneration, under prolonged treatment with D-penicillamine, presented with a circular or serpiginous arrangement of nuchal papules. Histopathologically, transepidermal channels were accompanied by granulomatous reactions, with several giant cells engulfing elastic fibers. In addition to these findings of a typical elastosis perforans serpiginosa, we observed scar-like skin changes inside the circular arrangement of the papules. At the scar-like tissue, we found electron-microscopical evidence of randomly aggregated thin collagen fibers with no tendency toward systemic combined bundle formation, which is a characteristic feature of normal collagen fiber formation. Pseudoxanthoma-elasticum-like changes were observed on his neck. On his axillae and groin, slight skin thickening and wrinkling were detected. The diagnosis of elastosis perforans serpiginosa does not represent all of the manifestations or the pathological background described above. The skin manifestations described here represent not only an elastosis but also a total degenerative dermatosis with over-healed collagenosis. Thus, those dermatoses should be summarized as one entity, penicillamine-induced degenerative dermatosis. After considering the pathogenic background and clinical similarities, we further propose to simplify the penicillamine-induced skin manifestations to three categories: acute sensitivity reactions, bullous dermatoses, and degenerative dermatoses.     

Expression of cell-matrix molecules and integrin receptors in human liver grafts during chronic rejection

Abstract The inflammatory response of immune cells to target cells and cell-matrix molecules is regulated by several receptor-ligand molecules. As fibrosis develops in ongoing chronic rejection after liver transplantation, it is of interest to analyze patterns of integrin receptors and cell-matrix molecules in order to study the relation between immune cells and the stromal and parenchymal cells. In the present study, we demonstrated the expression of these molecules in chronic rejected human liver grafts using immunohistochemical techniques. The results showed a differential expression and induction of integrin receptors and cell-matrix molecules on resident liver cells, especially on sinusoids, reflecting a state of chronic inflammation and a specific interaction between integrin receptors and cell-matrix molecules. The patterns of induced integrin receptors on graft-infiltrating cells was closely related to the local production of cell-matrix molecules and reflected the final sequence of a stepwise progress of the inflammatory reaction.     

Mechanisms of the biphasic responses to endothelin-3 in dog coronary arteries.

1. Endothelin-3 (ET-3) elicited relaxations at low concentrations (up to 10(-8) M) and contractions at higher concentrations in dog isolated coronary arteries precontracted with prostaglandin F2 alpha (PGF2 alpha). The relaxation by ET-3 was not affected by endothelium denudation nor treatment with NG-nitro-L-arginine, but was abolished or reversed to a contraction by treatment with indomethacin and markedly suppressed by tranylcypromine, a PGI2 synthetase inhibitor, or diphloretin phosphate, a prostaglandin receptor antagonist. ET-1 produced only concentration-dependent contractions. 2. BQ-123, a new selective ETA receptor antagonist, caused relaxation of the strips contracted with ET-3 in a dose-dependent manner and prevented the ET-3-induced contraction but did not affect the contraction produced by PGF2 alpha. The relaxation caused by ET-3 was enhanced by treatment with BQ-123. 3. It is concluded that the relaxations elicited by ET-3 in dog coronary arteries are mediated via liberation of PGI2 by activation of non-ETA receptors, located in subendothelial tissues, possibly smooth muscle cells, whereas the peptide-induced contractions are mediated via ETA receptors.     

Estrogenic Induction of NADPH- Diaphorase Activity in the Preoptic Neurons Containing Estrogen Receptor Immunoreactivity in the Female Rat

Nitric oxide and estrogen have been shown to play a critical role in the control of female reproductive function. In order to determine an anatomical relationship between nitric oxide generating neurons and estrogen target neurons, NADPH-diaphorase histochemistry was combined with estrogen receptor immunohistochemistry in the female medial preoptic area. While only a few weakly stained neurons for NADPH-diaphorase were found in ovariectomized control rats, a drastic increase in NADPH-diaphorase activity was observed in the medial preoptic nucleus of estradiol-treated ovariectomized animals. The total number of NADPH-diaphorase neurons in the estradiol-treated group increased three-fold relative to controls, and more than 80% of those neurons contained estrogen receptor-immunoreactivity in their nuclei. Since neuronal NADPH-diaphorase is nitric oxide synthase, the present result suggests that nitric oxide synthase activity can be positively regulated by estradiol in neurons containing estrogen receptor in the female medial preoptic nucleus.     

Prognostic value of blood glucose in patients with cardiogenic shock.

BACKGROUND: Although an elevated blood glucose has prognostic value in cardiovascular disease, few data are available regarding its prognostic value for patients across the spectrum of cardiogenic shock. METHOD AND RESULTS: A total of 81 patients with cardiogenic shock whose blood glucose and adrenaline were measured on arrival at the emergency room (ER) were enrolled in this prospective study. The primary endpoint was death from any cause in hospital. The rate of death was 12.3% (10/81), and the glucose level was lower among patients who were discharged alive than among those who died (8.7+/-3.7 mmol/L vs 13.8+/-6.7 mmol/L, p<0.001). The unadjusted rate of death increased in a stepwise fashion among patients in increasing quartiles of glucose level (p<0.05). The blood glucose level of 9.2 mmol/L had the highest combined sensitivity and specificity for the identification of death. In the multiple logistic-regression analysis for the primary outcome, the adjusted odd ratio for a glucose level of 9.2 mmol/L or more was 5.8 (95% confidence interval, 1.0-32.8, p=0.047). There was a significant positive correlation between the glucose and adrenaline levels (R=0.726, p<0.0001). CONCLUSION: The measurement of blood glucose level on ER arrival provides predictive information for use in risk stratification across the spectrum of cardiac emergencies complicated by cardiogenic shock.     

Influence of Hemorrhagic Shock Followed by Crystalloid Resuscitation on Propofol: A Pharmacokinetic and Pharmacodynamic Analysis

Background: Previous work has demonstrated that ongoing hemorrhagic shock dramatically alters the distribution, clearance, and potency of propofol. Whether volume resuscitation after hemorrhagic shock restores drug behavior to baseline pharmacokinetics and pharmacodynamics remains unclear. This is particularly relevant because patients suffering from hemorrhagic shock are typically resuscitated before surgery. To investigate this, the authors studied the influence of an isobaric bleed followed by crystalloid resuscitation on the pharmacokinetics and pharmacodynamics of propofol in a swine model. The hypothesis was that hemorrhagic shock followed by resuscitation would not significantly alter the pharmacokinetics but would influence the pharmacodynamics of propofol.

Methods: After approval from the Animal Care Committee, 16 swine were randomly assigned to control and shock-resuscitation groups. Swine randomized to the shock-resuscitation group were bled to a mean arterial blood pressure of 40 mm Hg over a 20-min period and held there by further blood removal until 42 ml/kg of blood had been removed. Subsequently, animals were resuscitated with lactated Ringer's solution to maintain a mean arterial blood pressure of 70 mm Hg for 60 min. After resuscitation, propofol (750 [mu]g[middle dot]kg-1[middle dot]min-1) was infused for 10 min. The control group underwent a sham hemorrhage and resuscitation and received propofol at the same dose and approximate time as the shock-resuscitation group. Arterial samples (20 from each animal) were collected at frequent intervals until 180 min after the infusion began and were analyzed to determine drug concentrations. Pharmacokinetic parameters for each group were estimated using a three-compartment model. The electroencephalogram Bispectral Index Scale was used as a measure of drug effect. Pharmacodynamics were characterized using a sigmoid inhibitory maximal effect model.

Results: The raw data demonstrated minimal differences in the mean plasma propofol concentrations between groups. The compartment analysis revealed some subtle differences between groups in the central and slow equilibrating volumes, but the differences were not significant. Hemorrhagic shock followed by resuscitation shifted the concentration effect relationship to the left, demonstrating a 1.5-fold decrease in the effect-site concentration required to achieve 50% of the maximal effect in the Bispectral Index Scale.     

NEW METHOD OF STENTING TREATMENT FOR MALIGNANT DUODENAL STENOSIS: USING DOUBLE‐BALLOON ENTEROSCOPY

Recently, a self‐expandable metallic stent has been recognized for treatment of malignant duodenal stenosis. But the complications by stenting are important problems even now. In the present study, we report our new method of duodenal stenting by using of double‐balloon enteroscopy considered safe and effective.     

Enzyme-linked Immunosorbent Assay of Pro-gastrin-releasing Peptide for Small Cell Lung Cancer Patients in Comparison with Neuron-specific Enolase Measurement

Our previous study demonstrated that pro-gastrin-releasing peptide(31–98), or ProGRP, is a specific tumor marker in patients with small cell lung carcinoma (SCLC). Using a newly developed, highly sensitive enzyme-linked immunosorbent assay (ELISA) for ProGRP, we analyzed 1,446 samples including those obtained from 478 lung cancer patients to evaluate the clinical usefulness of this ELISA. Several properties indicated that ProGRP is a useful tumor marker for SCLC. First, ProGRP was specifically elevated in SCLC patients. In non-SCLC patients and patients with non-tumorous lung diseases, its serum level was very rarely elevated. Secondly, ProGRP was a reliable marker, in terms of the marked elevation of serum ProGRP levels in SCLC patients. Thirdly, serum ProGRP levels were elevated in SCLC patients even at a relatively early stage of this disease. Fourthly, changes in the serum ProGRP level showed an excellent correlation with the therapeutic responses in SCLC patients. Neuron-specific enolase (NSE) is accepted as a tumor marker of SCLC patients. With the aim of comparing ProGRP and NSE as tumor markers for SCLC patients, we measured serum NSE levels in all samples collected in the present study. We found that ProGRP was superior to NSE in terms of sensitivity, specificity and reliability. Therefore, we consider that ProGRP can play a major role as a clinical tumor marker for SCLC patients.     

Disappearance of Philadelphia chromosomes after remission induction in lymphoid crisis of chronic myelogenous leukemia]

The authors report a rare case of chronic myelogenous leukemia (CML) in which the Ph1 clone disappeared after remission induction of lymphoid crisis. A 58-year-old man was admitted to our hospital because of fever in July 1988. The white cell count was elevated. Bone marrow aspirate showed hypercellularity with myeloid hyperplasia. In the chromosomal analysis, Ph1 chromosomes were detected in 100% of bone marrow cells analysed. Diagnosis of CML was made and treatment was initiated with recombinant interferon-alpha 2a. Hematological remission without cytogenetic improvement was achieved. In March 1990 he developed lymphoid crisis with proliferation of CD10-positive cells. The chromosomal analysis revealed additional abnormalities including, 45, X, -Y, t(9;22) (q34;q11), +1, -8. With vincristine 0.6 mgX4, pirarubicin 15 mgX4, dexamethasone 40 mgX4 therapy complete remission was obtained. In December 1990 the Ph1 positive clone completely disappeared judging from normal karyotypes in the chromosomal analysis and the disappearance of M-bcr gene rearrangement.