Quantitative assessment of impairment in constructional ability by cube copying in patients with aphasia

Constructional apraxia was evaluated in patients with aphasia using a cube-copying task. It was assessed whether quantitative assessment of cube copying could be used to estimate the performance intelligence quotient (IQ) according to neuropsychological tests. Abnormality in the cube-copying test was observed in 42 of 46 patients (91.3%). Performance according to Raven's coloured progressive matrices and the revised Wechshler adult intelligence scale (WAIS-R) in patients with poor cube copying was significantly lower than in the other four patients. Numbers of the connections completed and plane-orientation errors made in the cube-copying test were significantly correlated with performance IQ on the WAIS-R, correlating particularly with block design, digit symbol, and object assembly in performance IQ subtests. The quantitatively scored cube-copying test, then, can roughly predict non-verbal IQ in patients with aphasia.     

Laparoscopic adrenalectomy for pheochromocytoma: morbidity compared with adrenalectomy for tumors of other pathology

PURPOSE: We report our experience with laparoscopic adrenalectomy in nine patients with pheochromocytoma and compare the morbidity with that of laparoscopic adrenalectomy for tumors of other pathology. PATIENTS AND METHODS: Between January 1997 and November 1999, nine patients underwent laparoscopic surgery for pheochromocytoma via a transperitoneal approach. Of the patients, eight had solitary tumors, and one presented with bilateral pheochromocytomas. The mean size of the tumors was 5.4 cm. The surgical outcomes of the 9 patients were compared with those of 28 patients with adrenal tumors of other pathology (primary aldosteronism in 15 patients, Cushing syndrome in 6, and nonfunctioning adenoma in 7) who underwent transperitoneal laparoscopic adrenalectomy during the same period. The mean size of the adrenal tumors of other pathology was 2.4 cm. RESULTS: In eight of the nine patients with pheochromocytoma, laparoscopic adrenalectomy was successful. The procedure was converted to open surgery in the patient with bilateral tumors because of uncontrollable hemorrhage. A hypertensive crisis with the systolic blood pressure >200 mm Hg occurred in 6 patients (67%), but the episode could be controlled by temporary discontinuation of tumor manipulation, administration of drugs, or both. In adrenalectomy for pheochromocytoma, the mean operative time was longer (199 v 177 minutes) and the mean estimated blood loss was greater (360 v 54 mL) than for tumors of other pathology. Blood transfusion was given to two patients with pheochromocytoma but to no patient with tumors of other pathology. The patients with adrenal tumors of other pathology could resume normal activity earlier (mean 18 v 26 days) than those with pheochromocytoma. CONCLUSION: The operation is more difficult and the morbidity is higher in laparoscopic adrenalectomy for pheochromocytoma than that for tumors of other pathology. An experienced team of surgeons with advanced laparoscopic skills and anesthesiologists is mandatory. In large tumors, great caution should be taken for intraoperative complications. Nevertheless, laparoscopic adrenalectomy is not contraindicated for pheochromocytoma and can be performed safely.     

Invasive Ductal Carcinoma of the Breast Associated with Poland's Syndrome: Report of a Case

We report herein a rare case of invasive ductal carcinoma of the breast associated with Poland's syndrome. The patient was a 59-year-old woman who was referred to our department after a nodule had been found in the upper outer portion of the left breast by a breast cancer screening program. On physical examination, marked hypoplasia of the right breast and upper limb was noted. Preoperative computed tomography also revealed a defect in the right pectoralis muscles. A quadrantectomy of the left breast with lymphadenectomy was subsequently performed and pathological examination of the resected specimen showed invasive ductal carcinoma. Her medical history revealed that her mother had attempted to abort the pregnancy around the fifth week of her gestation. The present case suggests that such an event during gestational development may be associated with congenital anomalies predisposing to malignant disorders. Received: January 10, 2001 / Accepted: July 17, 2001     

Studies on the metabolic fate of M17055, a novel diuretic (6). Assessment for drug-drug interactions of M17055 in metabolism,distribution and excretion

1. The potential of M17055, a novel diuretic candidate, to affect the activities of human CYP enzymes, alter the plasma unbound fraction and compete with concomitant drugs in renal secretion as part of an assessment for drug-drug interactions in metabolism, distribution and excretion was investigated. 2. The effects of M17055 on the activities of human CYP1A2, CYP2E1, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 were considered negligible at clinically relevant concentrations. 3. The majority of M17055 (99%) was bound to human plasma proteins, but it is unlikely to alter the binding of other clinically relevant drugs. 4. The renal clearance of M17055 (corrected for the plasma unbound fraction in male rats) substantially exceeded the glomerular filtration rate and was markedly reduced by treatment with probenecid, suggesting that the renal excretion of M17055 is controlled predominantly by an active secretion mechanism. 5. The results show that M17055 is unlikely to cause or undergo significant pharmacokinetic interactions with concomitant drugs in metabolism and distribution. However, when it is administered simultaneously with certain organic anions, drug-drug interactions during kidney excretion may be possible.     

Lack of interaction between amiodarone and mexiletine in cardiac arrhythmia patients

Amiodarone has pharmacokinetic interactions with various therapeutic agents, including phenytoin, flecainide, and cyclosporine. Mexiletine is metabolized by CYP2D6 and CYP1A2. The objective of this study is to evaluate the effect of amiodarone on the pharmacokinetics of mexiletine through its inhibition of various cytochrome P450 (CYP) subtypes. In a series of 181 inpatients with supraventricular tachyarrhythmias, 26 inpatients received mexiletine and amiodarone therapy (MEX + AMD group), and the others received mexiletine therapy (MEX group). In 10 inpatients of the MEX + AMD group, the mexiletine clearance (CL(MEX)/F) before and after coadministration of amiodarone was compared. CL(MEX)/F was also compared in the MEX and MEX + AMD groups after the start of amiodarone therapy. Serum mexiletine, amiodarone, and desethylamiodarone concentrations were measured by an HPLC method. The CL(MEX)/F was estimated by the Bayesian method using population pharmacokinetic analysis. There was no significant difference in CL(MEX)/F before and after 1-month coadministration of amiodarone in 10 inpatients of the MEX + AMD group. Although serum amiodarone and desethylamiodarone concentrations gradually increased with time after the start of amiodarone therapy in these patients, CL(MEX)/F showed no change at 3 and 5 months after the start of amiodarone therapy. There was no significant difference in CL(MEX)/F of the MEX group and the MEX + AMD group. The results suggest that the pharmacokinetics of mexiletine is not affected by amiodarone in patients with cardiac arrhythmias.     

Val-Tyr as a natural antihypertensive dipeptide can be absorbed into the human circulatory blood system

1. Intact absorption of the bioactive dipeptide Val-Tyr (VY), with in vivo antihypertensive ability in normotensive human subjects, was investigated. 2. As a result of a single oral administration of VY, the VY absorption curve occurred maximally over the second hour postprandially; a greater than 10-fold higher increment of VY following a dose of 12 mg was observed in the plasma at 2 h compared with the baseline concentration of VY at 0 h (1934 +/- 145 vs 159 +/- 11 fmol/mL plasma, respectively). 3. Plasma VY levels increased with dose administered (3, 6 and 12 mg), suggesting that exogenous VY could be absorbed intact into the human blood depending on the dose. The elimination half time (t1/2) of VY was estimated to be 3.1 h. The area under the curve for the 12 mg VY dose was 9185 +/- 688 fmol small middle doth/mL plasma.     

Pharmacokinetic and clinical studies on teicoplanin for sepsis by methicillin-cephem resistant Staphylococcus aureus in the pediatric and neonate field

Pharmacokinetics, clinical efficacy and safety of teicoplanin (TEIC) were evaluated in pediatric and neonate patients with MRSA sepsis in the dosages approved in overseas. The administrated dose for pediatrics patients was 10 mg/kg once at hour 0, 12 and 24, followed by every 24 hours intervals. In neonates patients, first dose was 16 mg/kg, then 8 mg/kg every 24 hours intervals. 1. Pharmacokinetic results. All 17 patients (9 neonates and 8 pediatrics) who received TEIC were evaluated for pharmacokinetics. Trough concentrations were analyzed in 16 patients (9 neonates and 7 pediatrics) excluding one patient for lack of measurement of drug concentration at day 7. No patient with a concentration exceeding 60 micrograms/mL in peak or trough concentrations were reported. Mean concentrations in trough at day 3, 4 and 7 in neonates were 15.2, 14.7 and 17.8 micrograms/mL, and in pediatrics were 12.5, 12.2 and 13.1 micrograms/mL, respectively. These results were similar to those reported in foreign pediatrics and neonates patients. 2. Efficacy and safety results. Since no patient was excluded, all patients were evaluated for efficacy and safety. Microbiological efficacy as well as clinical cure were secondarily evaluated in 2 patients for whom MRSA was isolated from blood. Clinical efficacy rate was 76.5% (13/17) and number of cases in judgments of excellent, good, fairly improved and no change were 12, 1, 3 and 1 cases respectively. The patients for whom MRSA was isolated from blood were judged as MRSA eradicated case and cured without any additional anti-MRSA drugs. Adverse events were reported in 2 neonates and 3 pediatric patients. Possibly related adverse events to study drug (adverse drug reactions) were: 1 case of respiratory disorder, thrombocythemia, gamma-GTP increased, GOT increased and GPT increased in 3 pediatrics. These results suggest that an application of overseas dose regimen of TEIC for neonate and pediatrics is appropriate in Japan.     

Effects of amifostine on the proliferation and differentiation of megakaryocytic progenitor cells

This study investigated the effects of amifostine, a clinically usable radioprotector or chemoprotector, on the proliferation and differentiation of normal and X-irradiated cluster of differentiation 34 positive (CD34+) megakaryocytic progenitor cells (colony-forming unit in megakaryocytes, CFU-Meg) from human placental and umbilical cord blood (CB) in vitro. Amifostine significantly accelerated megakaryocyte colony formation in a plasma clot culture supplemented with recombinant human thrombopoietin because of an increase in immature CFU-Meg-derived large megakaryocyte colony formation. An analysis of the cells that were harvested from the culture showed that amifostine induced a 70- and an 83-fold increase in the total cell and CFU-Meg numbers, respectively, and produced hyperploid megakaryocytes of more than 8 N ploidy. The radioprotective effect of amifostine on the clonal growth of X-irradiated CD34+ CFU-Meg was observed by treatment before or after irradiation. These findings suggest that the action of amifostine extends from immature CFU-Meg to the terminal differentiation of megakaryopoiesis, and its radioprotective effect is shown in megakaryopoiesis and thrombopoiesis.