Tomoki Okuda

Changes in Plasma Serotonin Concentration and Acceleration Plethysmograms in Patients with Raynaud's Phenomenon after Long‐term Treatment with a 5‐HT2 Receptor Antagonist

High blood serotonin concentrations have been reported in patients with Raynauds phenomenon and a relationship has been suggested. Because of the difficulty in evaluating Raynauds phenomenon objectively, a possible correlation between blood serotonin concentrations and clinical findings has not yet been evaluated. We measured plasma serotonin concentrations and acceleration plethysmograms (APG) before and one year after administration of a serotonin receptor antagonist. Twenty‐seven patients with either collagen disease or diseases associated with Raynauds phenomenon were given a combined 5‐HT2 and serotonin receptor antagonist, sarpogrelate hydrochloride. Plasma serotonin concentrations were determined before and after administration and the APG d/a value was measured as an index of peripheral hemodynamics. These values were compared with the clinical symptoms of the patients. After one year of treatment, the subjective symptoms improved in 59.3% of patients who has Raynauds phenomenon. The pre‐treatment plasma serotonin concentrations of the study patients were significantly higher than those of the normal controls, but became significantly decreased following 5‐HT2 administration. However, there was no clear‐cut relationship with the clinical symptoms. The pre‐treatment APG d/a value of the patients was significantly lower than that of the normal controls, although there was no significant difference after administration when analyzed as an entire group or in a subset of patients whose symptoms did not subjectively improve or worsened after one year of treatment. In the subset in whom the subjective symptoms improved, however, the value significantly increased following administration, suggesting an improvement in peripheral hemodynamics. These results suggest the possibility that APG can be used as an objective index of peripheral hemodynamics.

The occurrence of various collagen diseases in one family: a sister with ISSc, PBC, APS, and SS and a brother with systemic lupus erythematosus.

We encountered siblings who had collagen diseases and related symptoms. Case 1 was a 53‐year‐old woman who had limited cutaneous systemic sclerosis (ISSc) associated with primary biliary cirrhosis (PBC), antiphospholipid antibody syndrome (APS), and subclinical Sjögrens syndrome (SS). Case 2 was a 48‐year‐old man, her younger brother, with systemic lupus erythematosus (SLE) that developed at 32 years of age. Investigation of their family revealed that their mother had Raynauds phenomenon, arthritis, and subclinical Sjögrens syndrome, and that another younger brother of Cases 1 and 2 had Raynauds phenomenon and general fatigue. HLA analysis revealed that the sister and brother had some identical HLA antigens in common, including A2, A33 (19), B67, B44 (12), Cw7, DR2, DR6, DR52, and DQ1. The sister, brother and their mother had common HLA antigens including A2, B67, Cw7, DR2, and DQ1. Although Cases 1 and 2 shared the same HLA system, they presented different phenotypes of collagen disease.

A Case of Drug Eruption Caused by the Crude Drug Boi® (Sinomenium Stem/Sinomeni Caulis et Rhizoma)

We report a case of drug eruption caused by the crude drug Boi®. A 41‐year‐old female patient had been diagnosed with chronic rheumatoid arthritis in the department of internal medicine. After ingestion of a decoction of the crude drug Boi® for the alleviation of arthralgia, a slight fever developed, which was followed by systemic edematous erythema with itching. HPLC showed that the main components of the crude drug Boi® are sinomenine and magnoflorine. The results of patch tests were negative for all oral drugs that the patient had been taking. Oral ingestion tests showed that the patient showed positive reactions to the as‐is Boi® boiling‐water decoction and 1/10‐volume sinomenine. Based on this, the drug eruption was judged to be caused by sinomenine. It is considered the first time that the causative component of a drug eruption was confirmed by oral ingestion tests with components of a crude drug of Kampo medicine (Sino‐Japanese traditional medicine).

Cyclosporin A pharmacokinetics in a patient with psoriasis and obesity, presenting with high levels of low-destiny lipoprotein

Cyclosporin A (CyA), an immunosuppressant, is now frequently used for the treatment of psoriasis and its usefulness is widely known. This letter reports on an obese and hyperlipemic patient with psoriasis, where the metabolism of CyA was successfully normalized and efficacy was increased, followed by an improvement in the clinical symptoms when hyperlipemia was improved. The patient was a 51-year-old Japanese woman with psoriasis vulgaris. In spite of treatment with a steroid for external use, eruption worsened. Oral administration of CyA at a daily dose of 2 mg/kg, which was started thereafter, also led to no improvement in eruption. Hyperlipemia type IIa was diagnosed on the basis of blood analysis. When fluvastatin (FV) was combined with CyA, a remarkable improvement in eruption was found. Lipid metabolism was therefore considered to be involved in the effect and pharmacokinetics of CyA. To study the reasons why a high-trough level was reached after administration of CyA at a dosage of 2 mg/kg/day and why eruption was remarkably improved after oral administration of FV, the pharmacokinetics of CyA were also measured. The patient was orally administered CyA (2 mg/kg) after breakfast and the CyA monoclonal whole blood values were determined; the radioimmunoassay (RIA) concentration was measured 1, 2, (3), 4, 6, 12, and 24 h later [6 (7) times in total]. In addition, the blood was sampled in the morning after fasting to determine the levels of triglyceride (TG), total cholesterol (T-chol), low-density lipoprotein (LDL), and so forth. The levels of the serum lipids before oral administration of FV were high, that is, T-chol of 270 mg/dl and LDL-chol of 204 mg/dl. The pharmacokinetics of CyA showed a high-trough level of 300 ng/dl and the blood CyA concentration did not decrease even 15 h after oral administration (24 h after oral administration of CyA, the blood CyA concentration was also abnormally high, at 270 ng/ml).

Evaluation of Acceleration Plethysmograms in Dermatology—Efficacy of Lipo PGE1 Preparations against Herpes Zoster and Neuralgia Following Herpes

Reports published in recent years indicate that administration of lipo PGE1 is effective against herpes zoster and neuralgia following herpes. However, there are presently no standards to objectively assess efficacy. We therefore looked into the possibility of achieving this goal by using an acceleration plethysmograph. The results showed a significant difference in the rate of change of pulse waves after initiation of drip infusion as compared to before drip infusion among the effective group, the control group, and the non‐effective group. This method appears to be useful to objectively assess both the analgesic effects of lipo PGE1 and the efficacy of drugs in general, based on data analysis. Our results suggest that investigations using this method may be able to predict the therapeutic effects of vasodilators and analyze hemodynamic disorders of the skin.

An experimental study of vascular dynamics by an acceleration plethysmogram using artificial circulation devices

Plethysmogram has been widely known as a conventional non-invasive simple method to obtain information on peripheral circulatory kinetics. We made a quantitative assessment of the relationships between the various circulatory parameters, using the simple conventional measurement method of treating acceleration plethysmograms (the second derivatives of digital plethysmograms) as indicators of peripheral circulation kinetics. We designed a prototype model peripheral circulatory circuit, using an artificial heart, for the purpose of clarifying the relationship between physical factors and plethysmograms. In our models of the peripheral circulatory system, we made use of various types of matching silicon tubes, as well as canine carotid arteries, as substitutes for human arteries. We evaluated the mechanical characteristics, such as the pressure and volume characteristics of the silicon tubes and canine carotid arteries. Plethysmogram alterations were measured using a photoelectric digital plethysmogram. When we examined the acceleration plethysmogram b/a values, which indicate blood vessel extensibility and hardness, and the d/a values, which we were able to use as an index of peripheral circulatory kinetics, it was clear from out model testing that canine carotid arteries displayed b/a values that were closest to those found in the human fingertip; among artificial tubes, the closest was a tube with a diameter of 4 mm (0.18 mm in thickness). The b/a values of all types of tubes declined when the compliance of the arterial system was increased, and it was confirmed through model testing that b/a values are an indicator of blood vessel extensibility.

A case of giant metastatic malignant melanoma.

We report a rare case of giant metastatic malignant melanoma (GMMM). A 52-year-old man had noticed a small nodule on the top of his head about one year previously. When he visited our hospital on March 18, 1998, the dome-shape nodule measured 30×30mm and was accompanied with satellite lesions. Excisional biopsy of satellite lesion yielded a histopathological diagnosis of malignant melanoma (MM). There were no findings of systemic metastasis. We classified this as MM (pT4bN0M0, Clark level V, Stage III) . After we injected IFN β into the lesion, we perfomed wide local excision. However, in this case, cutaneous metastasis appeared on the left neck 5 months lates MM. He had received DAV-IFN β therapy for the lesion. However, after three courses of adjuvant therapy, the neck metastasis did not decrease. He died of the disease one year and 9 months after the operation. Very few cases of GMMM have been reported to gradually enlarge reaching a size of 330×220×115mm. [Skin Cancer (Japan) 2000; 15: 147-151]