Late-onset type ornitine transcarbamirase deficiency (OTCD) with fulminant onset following a fatal prognosis]

A 16-year-old man was admitted to our hospital with nausea, general fatigue, and consciousness disturbance along with extreme hyperammoniemia eight days after the onset of symptoms. Familial history and the high concentration of orotic acid in urine lead us to a diagnosis of OTCD. We immediately initiated intensive treatment such as continuous hemodiafiltration and sodium benzoate administration; however, the patient died twelve days after admission. Since OTCD is not so rare and can be found in all ages, it should be considered fundamental for evaluation of hyperammoniemia. This case suggested that for a better prognosis of OTCD patients it is very important to prevent such an onset, and to make an as early as possible diagnosis and start to treatment.     

Binding characteristics of 3H-CGP12177 to beta-adrenoceptors in rat myocardial membranes

The present study was designed to examine the selectivity of 3H-CGP-12177 (4-(3-t-butylamino-2-hydroxypropoxy)-[5,7-3H]benzimidazole-2-one hydrochloride) for beta 1- and beta 2-adrenergic receptors by the Scatchard and the displacement analysis. The plots of specific binding obtained from the Scatchard analysis using 3H-CGP12177 for the rat myocardium membrane were uniphasic when the non-specific binding was determined by the use of 10 microM I-propranolol, and the Kd and Bmax values were 408.53 +/- 67.20 pM and 12.27 +/- 0.83 fmoles/mg protein, respectively. On the other hand, two binding sites were observed in the displacement curve when I-metoprolol was used as a competitor. The existence of these two binding sites implied the selectivity of 3H-CGP12177 to beta-adrenoceptors because 3H-CGP12177 was 1.8-fold more selective towards beta 1-adrenoceptors than beta 2-adrenoceptors. In addition, these two binding sites could be regarded as beta 1- and beta 2-adrenergic receptors from the evaluation of the binding characteristics beta-adrenoceptors by the displacement analysis using beta-selective antagonists. Thus, 3H-CGP12177, a hydrophilic radioligand, was useful for the binding assay of beta-adrenoceptors in rat myocardial membranes.     

Traumatic acute subdural hygroma mimicking acute subdural hematoma.

Subdural hygroma is a frequent delayed complication of head trauma. Most hygromas are clinically 'silent' and a few cases have shown slow deterioration in the chronic stage. We report a case of subdural hygroma showing unique radiological findings and rapid deterioration. A 74-years-old female presented with a mild headache and consciousness disturbance after head injury. Computed tomography showed a midline shift as a result of two components piling up in the subdural space; the outer components showed low density, the inner components high density. Magnetic resonance imaging demonstrated that these two subdural components were subdural hygroma and subarachnoid hematoma. Simple burr hole irrigation, rather than large craniotomy, was thought to be more appropriate treatment to reduce the mass effect. Simple burr hole irrigation was performed to remove the subdural hygroma and the patient showed an excellent recovery. Careful examination of the radiological findings prevented an unnecessary procedure in this case. A possible mechanism of this phenomenon is discussed.     

Evaluation of blood flow patterns of true and false lumens in dissecting aneurysms using MR phase-contrast techniques

The magnetic resonance phase-contrast technique for the measurement of flow velocity and volume in true and false lumens was studied in six patients with chronic dissecting aneurysms. Phase-contrast images were obtained at a level perpendicular to the dissecting aneurysms of the descending aorta. As the maximum diameter of aneurysms increased, the ratio of the cross-sectional area of the false to the true lumen increased and the peak average velocity in the true lumen during systole was decreased. This technique proved invaluable for determining prognosis and operability for this condition.     

Thrombocytosis in preterm infants: a possible involvement of thrombopoietin receptor gene expression

Transient thrombocytosis is commonly observed in preterm infants after birth, but its physiological mechanism is still unknown. To understand the mechanism of the transient thrombocytosis in preterm infants we firstly evaluated a correlation between platelet counts and thrombopoietin (TPO) levels in preterm infants and next c-mpl mRNA levels on platelets in healthy preterm infants longitudinally during a half-year of life. The mean platelet counts in 45 very low birth weight infants (mean gestational age 27.4±1.8 weeks, mean birth weight 1047±249 g) was 230±71×10⁹/l just after birth and thereafter gradually increased to 579±178×10⁹/l by 5 weeks of age. The platelet counts continued this level for about next 8 weeks. Serum TPO levels soon after birth and at 1 month of age were significantly higher than those at the age of 2–6 months. There was a significant negative correlation between platelet counts and serum TPO values. The c-mpl expression levels on platelets at birth and at 1 month of age tended to be lower than those on platelets from adults, and the c-mpl levels gradually increased through 6 months of age, although they were still lower than those of adults. Our results suggest that low expression of TPO receptor on platelets until 1 month after birth cause a decreased TPO clearance and keep a high level of free TPO in blood, thereby promoting platelet production from megakaryocytes or their progenitors in bone marrow, resulting in the subsequent thrombocytosis in preterm infants.     

Acupuncture needles, straying in the central nervous system and presenting neurological signs and symptoms

Acupuncture has been practiced in the treatment of many diseases in Japan. "Okibari" is one of the procedures in acupuncture treatment: a fine stainless steel or silver needle is inserted into the subcutaneous tissue through the skin, to remain in the subcutaneous tissue. A 57-year-old pharmacist was knocked down by a motorcycle in 1971, since then moderate weakness of left extremities and stiffness of muscles have remained as sequelae. She was consequently treated with acupuncture. Many small needles were inserted permanently in the nuchal, occipital and other areas of the body ten to twelve years before she developed gradual clumsiness and dysesthesia in her right hand in 1984. When she was admitted for the first time in 1985, neurological examination revealed left Horner's syndrome and diminished deep sensation in her right extremities with pseudo-athetosis of her right hand, along with spastic paresis of left extremities and right carpal tunnel syndrome. An old needle which had strayed into left dorsal medulla was considered to be responsible for these symptoms. In 1988 loss of pain and temperature sensation in the right side of her body below the shoulder, and diminished deep sensation of left extremities were appended, and weakness of her left extremities became aggravated. Pseudo-athetosis of her right hand was seen less prominently. In plain X-ray films many needle shadows were visualized. On CT scan needle shadows could be seen also in the left dorsal medulla, right cerebellum and in the subarachnoid space of left dorsal C1-C2 level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Identification of binding sites of bopindolol and its two metabolites with beta1-adrenoceptors by molecular modeling: comparison with beta2 adrenoceptors

This study was designed to examine the importance of interaction in the bindings of nonselective beta-blockers to beta1-adrenoceptors (beta1-ARs) as compared with beta2-ARs, using molecular modeling. The beta-blockers used in this study were bopindolol [4-(benzoyloxy-3-t- butylaminopropyl)-2-methylindol hydrogen malomate], its two metabolites [18-502 - hydrolyzed bopindolol or 4-(3-t-butylamino-2-hydroxypropoxy)-2-methyl indole - and 20-785 - 4-(3-t-butylaminopropoxy)-2-carboxyl indole], and propranolol. Molecular modeling was performed on an Indigo2 workstation (Silicon Graphic) using Discover/Insight II (Molecular Simulations) software. Through molecular modeling, possible binding sites for these drugs were suggested to lie between helices 3, 4, 5, and 6 of the beta1-AR. The amine, benzoic acid, indole methyl, t-butyl, phenyl, and indole functional groups of bopindolol possibly interact with Asp138 (transmembrane - TM - 3), Ser190 (TM 4), Ala343 (TM 6), Val137 (TM 3), Pro339 (TM6), Cys336 (TM 4), Leu237 (TM 5), and Pro236 (TM 5) of beta1-AR, respectively, by either hydrogen bonding or hydrophobic interactions. In addition, 18-502, 20-785, and propranolol also interacted with sites at the same positions as those of beta2-ARs. Thus, the results of the present study suggested that although Ala343 and Val137 of beta1-AR among these amino acids were different from those of beta2-AR, the interactions at the same sites between ligands and amino acids of beta1-AR as those of beta2-ARs may occur because these drugs are nonselective.     

Prediction of carboplatin clearance calculated by patient characteristics or 24-hour creatinine clearance: a comparison of the performance of three formulae

Purpose: Carboplatin doses can be individualized using the formula of Calvert et al. (Calvert formula) dose (mg) = area under the plasma concentration versus time curve (AUC) · [glomerular filtration rate (GFR) + 25]. Creatinine clearance (Ccr), either measured by the 24-h method or calculated by the formula of Cockcroft and Gault [Cockcroft-Gault (CG) formula], is often substituted for the GFR. The CG formula is based on patient weight, age and sex, and the serum creatinine (Cr) concentration. Another method for predicting carboplatin clearance (CL) using patient characteristics has also been proposed by Chatelut et al. (Chatelut formula). This study was undertaken to evaluate the performance of the three formulae in predicting standard- and low-dose carboplatin pharmacokinetics. Methods: A total of 52 patients with advanced lung cancer were enrolled in this pharmacokinetic study; 37 received standard-dose carboplatin and 25 received low-dose carboplatin. The Cr concentration was measured using an enzymatic assay. The three formulae were used to predict carboplatin CL. The median absolute percent error (MAPE) for each formula was evaluated by comparing the calculated and observed CL. For comparison of AUCs, free platinum plasma concentrations were measured at intervals up to 24 h after carboplatin administration. AUCs were determined and compared with predicted values. Results: In the standard-dose carboplatin group, the MAPEs for the prediction of carboplatin CL from the 24-h Calvert, CG-Calvert and Chatelut formulae were 13%, 12% and 23%, respectively. In the low-dose carboplatin group, the corresponding MAPEs were 27%, 18% and 44%, respectively. Observed standard-dose carboplatin AUCs after aiming for target AUCs of 5 and 6 mg · min/ml using the Calvert formula based upon the 24-h Ccr were 5.3 ± 0.8 and 5.9 ± 0.8, respectively, indicating a small and acceptable bias compared with that predicted from the dosing formula. Conclusions: The pharmacokinetics of standard-dose carboplatin were accurately predicted by the Calvert formula based upon either 24-h or CG-calculated Ccr, but not by the Chatelut formula. Either CG-calculated or 24-h Ccr can be substituted for the GFR in the Calvert formula for the determination of individual doses. The poor predictability of the Chatelut formula found in this study might be the result of a differences in either the Cr assay or the patient population. Therefore, formulae which attempt to estimate GFR are not necessarily valid if either the Cr assay or the patient population is changed. Received: 23 July 1997 / Accepted: 16 December 1997