Optimum preparation of levocarnitine chloride solution in the hospital pharmacy

Levocarnitine chloride is used for the therapeutic purpose of levocarnitine deficiency. For infants, however, levocarnitine chloride tablets must be crushed to avoid difficulties associated with swallowing, and also to administer an appropriately low dosage. Since the tablet is extremely hygroscopic and sour, it is dissolved in water containing simple syrup after crushing. In this study we investigated the stability of the drug after dissolution to optimize its preparation for clinical use. It was shown to be stable for at least 90 days after preparation, and microbes did not grow in 1-10% (w/v) solutions (pH 2.0-2.5) regardless of the presence or absence of simple syrup. Furthermore, the autoclaved levocarnitine chloride solution was as stable as the non-autoclaved one. In conclusion, the method employed in our hospital for the preparation of levocarnitine chloride for infants is appropriate and is recommended as a standard medicine supply method among different facilities.     

Functional validation of the genetic polymorphisms of human ATP-binding cassette (ABC) transporter ABCG2: identification of alleles that are defective in porphyrin transport

The ATP-binding cassette (ABC) transporter ABCG2 has been implicated to play a significant role in the response of patients to medication and/or the risk of diseases. To clarify the possible physiological or pathological relevance of ABCG2 polymorphisms, we have functionally validated single nucleotide polymorphisms (SNP) of ABCG2. In the present study, based on the currently available data on SNPs and acquired mutations, we have created a total of 18 variant forms of ABCG2 (V12M, G51C, Q126stop, Q141K, T153M, Q166E, I206L, F208S, S248P, E334stop, F431L, S441N, R482G, R482T, F489L, F571I, N590Y, and D620N) by site-directed mutagenesis and expressed them in insect cells. Because porphyrins are considered to be endogenous substrates for ABCG2, we have investigated the porphyrin transport activity of those variant forms in vitro. We herein provide evidence that the variants Q126stop, F208S, S248P, E334stop, and S441N are defective in porphyrin transport, whereas F489L exhibited impaired transport, approximately 10% of the activity observed for the wild type. Furthermore, Flp-In-293 cells expressing those variants were photosensitive. Thus, among those genetic polymorphisms of ABCG2, at least the hitherto validated alleles of Q126stop, S441N, and F489L are suggested to be of clinical importance related to the potential risk of porphyria.     

Prediction of hepatic clearance and availability by cryopreserved human hepatocytes: an application of serum incubation method.

A novel and convenient method was established for the prediction of in vivo metabolic clearance in human liver. The present method applied the in vitro-in vivo extrapolation paradigm previously established in rats to the in vitro data obtained from cryopreserved human hepatocytes. Predicted hepatic availability and clearance were compared with the reported oral bioavailability and plasma clearance in humans for 14 clinically used drugs (naloxone, buspirone, verapamil, lidocaine, imipramine, metoprolol, timolol, antipyrine, diazepam, quinidine, caffeine, propranolol, diclofenac, and phenacetin). A large interindividual variation was observed in the intrinsic metabolic clearance among separate cryopreserved preparations from different subjects. The prediction generally resulted in a marked underestimation when the biologically based scaling factor (3.1 x 10(9) cells/kg) was used for the extrapolation of in vitro data (milliliters per minutes per cells) to in vivo value (milliliters per minutes per kilograms). Reasonably good in vitro-in vivo correlations were obtained with empirically calculated scaling factors, 8.5 x 10(9) (cells/kg) from 10 individual preparations and 10.8 x 10(9) (cells/kg) from pooled preparation of two selected lots, which were 3- to 4-fold larger than the biologically based scaling factor. These data suggested that the calibration of inherent interindividual variation of metabolic activities among different cryopreserved preparations of human hepatocytes to obtain the empirical scaling factor, which is applicable only to the preparation used, was an essential step for more reliable and quantitative prediction of in vivo metabolic activity in humans.     

Magnetic resonance imaging of intracranial venous angiomas

Magnetic resonance imagings (MRI) were made of intracranial venous angioma (six angiographically proved, four presumed). All draining veins were identified as a linear or a small round structure with a flow void. The stellate configuration was observed in seven of the ten patients. In two of the ten, the associated intraparenchymal hematoma was evident. Increased intensity of adjacent parenchyma on T2-weighted images was detected in four of ten patients, and a decreased intensity on the T1-weighted images was noted in three of eight. Thus, MRI is a pertinent diagnostic modality for evaluating intracranial venous angioma. Angiography does not seem to be required for confirmation in patients with typical MR findings.     

Vascular compression of the oculomotor nerve disclosed by thin-slice magnetic resonance imaging

Purpose: To describe the thin-slice magnetic resonance imaging features of vascular compressive oculomotor nerve paresis.Methods: We performed thin-slice (2 mm thick) magnetic resonance imaging of the brainstem in a 74-year-old woman with right partial oculomotor nerve paresis using spoiled gradient recalled acquisition in the steady state.Results: Thin-slice magnetic resonance images disclosed that the right oculomotor nerve was compressed and dislocated superiorly and laterally by the tortuous basilar artery. No other abnormalities were observed.Conclusion: This is the first case report of vascular compressive oculomotor nerve paresis disclosed by thin-slice magnetic resonance imaging.     

Multichannel near-infrared spectroscopy in depression and schizophrenia: cognitive brain activation study.

BACKGROUND: Recent developments in near-infrared spectroscopy (NIRS) have enabled the noninvasive clarification of brain functions in psychiatric disorders with measurement of hemoglobin concentrations as cerebral blood volume. METHODS: Ten patients with depression, 13 patients with schizophrenia, and 16 age- and gender-matched healthy control subjects participated in the study after giving consent. The relative concentrations of oxyhemoglobin [oxyHb] were measured with frontal and temporal probes every.1 sec during word fluency and unilateral finger tapping tasks, with two 24-channel NIRS machines. RESULTS: The [oxyHb] increase patterns during the word fluency task varied among the three groups, although their task performances were similar: the depression group was characterized by a smaller [oxyHb] increase during the first half of the task period and the schizophrenic group by a small trough of [oxyHb] at the start of the task period and [oxyHb] re-increase in the posttask period. [OxyHb] increases during the finger-tapping task were rather larger in the patient groups than in the control group. CONCLUSIONS: The characteristic time courses of [oxyHb] changes in the frontal lobe were elucidated for depression and schizophrenia. Near-infrared spectroscopy, with its noninvasiveness and high time resolution, can be a useful tool for research and clinical purposes in psychiatry.     

Effect of periarticular and intraarticular lidocaine injections for sacroiliac joint pain: prospective comparative study

Background The sacroiliac joint (SIJ) can be a source of low back pain. Previous studies indicated that SIJ pain could originate from both the joint capsule and the posterior ligamentous tissues. It has not been clarified as to whether an intraarticular or periarticular injection procedure is more effective for this type of pain. The purpose of this study was to evaluate the effect of two injection procedures prospectively. Methods After a pain provocation test, an intraarticular injection of local anesthetic (2% lidocaine) was performed on the first 25 consecutive patients with SIJ pain and a periarticular injection on another 25. The periarticular injections were given to one or more sections of the posterior periarticular area of the SIJ and to another section in the extracranial portion. The effect of these injections was assessed using the “restriction of activities of daily life” scoring system from the Japanese Orthopaedic Association. Results The periarticular injection was effective in all patients, but the intraarticular one was effective in only 9 of 25 patients. An additional periarticular injection was performed in 16 patients who experienced no effect from the initial intraarticular injection and was considered effective in all of them. The injection into the middle of the periarticular area was more effective for SIJ pain. The improvement rate after the periarticular injection was 96%, which was significantly higher than that after the intraarticular injection, which was 62%. Conclusions For patients with SIJ pain, periarticular injection is more effective and easier to perform than the intraarticular injection and should be tried initially.     

Defecographic assessment after colonic J pouch-anal anastomosis

Colonic J pouch anal anastomosis is widely employed after rectal resection. In the 36 patients who participated in our retrospective study, although postoperative continence was retained/maintained in each individual, a survey questionnaire indicated some difficulties in neoanorectal function. Therefore, defecography was performed in 20 of these patients. Patients experiencing soiling were found to have an increased ano-pouch angle and pelvic floor descent. Loss of sensation and incomplete evacuation were also associated with an abnormally large pelvic floor descent. However, stool frequency, urgency, and the need for medication showed no correlation with any of the defecography parameters. These findings thus suggested that the puborectal muscle and the levator ani muscle played an important role in postoperative function. Defecography was also found to provide a dynamic assessment of the postoperative state of colonanal reconstruction.