Reliability and validity of the Japanese version of the Yale-Brown Obsessive-Compulsive Scale

Abstract The reliability and validity of the Japanese version of the Yale-Brown Obsessive-Compulsive Scale (JY-BOCS) were determined by 20 raters for 12 Japanese patients with obsessive compulsive disorder at four institutions. Interrater reliability for the total JY-BOCS score was excellent, and the intraclass correlation coefficient was high (ICC = 0.960). Internal consistency was also excellent (Cronbach's α= 0.889). Concurrent and discriminant validity of the JY-BOCS was examined by comparing the scores on the JY-BOCS with those on the Maudsley Obsessional Compulsive Inventory (MOCI) and scales for depression and anxiety. A slight correlation was found between scores on the JY-BOCS and MOCI, but no significant correlations were found between scores on the JY-BOCS and those on scales for depression or anxiety.     

Effects of famotidine and cimetidine on plasma levels of epidurally administered lignocaine

The effects of two H2-receptor antagonists, famotidine and cimetidine, on the plasma levels of epidurally administered lignocaine were studied. Group A (n = 20) received famotidine 20 mg orally the night before surgery and 20 mg intramuscularly 60 minutes before induction of anaesthesia. Group B (n = 15) received cimetidine 200 mg orally the night before the surgery and 400 mg orally 60 minutes before the anaesthetic induction. Group C (n = 20) received neither famotidine nor cimetidine and served as controls. Twelve millilitres of 2.0% lignocaine with adrenaline 1:200,000 was injected into the epidural space in all patients, after the establishment of general anaesthesia with nitrous oxide, oxygen, and enflurane (0.3-0.5%). The patients who received cimetidine showed significantly higher plasma concentrations of lignocaine compared with either group A or group C at all investigation times (p less than 0.01). The mean peak plasma concentrations were 2.4 (SEM 0.1), 3.2 (SEM 0.2) and 2.3 (SEM 0.1) micrograms/ml in group A, B, and C, respectively. This study suggests that famotidine is preferable to cimetidine for control of gastric acidity before the use of lignocaine as the epidural anaesthetic.     

Direct Drug Transport from the Rat Nasal Cavity to the Cerebrospinal Fluid: the Relation to the Molecular Weight of Drugs

To clarify the relationship between the direct transport from the rat nasal cavity to the cerebrospinal fluid (CSF) and the molecular weight of the drug, the transport of fluorescein isothiocyanate-labelled dextran (FD) with various molecular weights was investigated. FDs (average molecular weights 4400 (FD4); 9400 (FD10); 18 900 (FD20); 40 500 Da (FD40)) were administered nasally or intravenously to rats, and the concentrations in the plasma and the CSF were measured and compared. None of the FDs were detected in the CSF after intravenous administration. However, FD4, FD10 and FD20 were observed to appear in the CSF after nasal administration, whereas the concentration in the plasma was much lower than that after intravenous administration. FD40 was not detected even after nasal administration. In addition, the concentration of these FDs in the CSF decreased with the increase in the molecular weight of FDs. These findings show that drugs with a molecular weight up to at least 20 000 Da can be directly transported from the nasal cavity to the CSF and that the transport of FDs to the CSF is dependent on their molecular weights.     

Post-tetanic count and single twitch height at the onset of reflex movement after administration of vecuronium under different types of anaesthesia

We have studied post-tetanic count (PTC) and single twitch heightat the onset of reflex movement to carinal stimulation afteradministration of vecuronium with five different types of anaesthesia.Seventy-five adult patients were allocated randomly to fivegroups of 15 patients each, to receive one of the followinganaesthetics: neuroleptanaesthesia (fentanyl and droperidol)or 1 MAC of either halothane, isoflurane, enflurane or sevofluranewith 66% nitrous oxide in oxygen. During spontaneous recoveryfrom vecuronium-induced neuromuscular block, the carina wasstimulated with a suction catheter every 150 s. Single twitchheights at the onset of reflex movement were similar (2.0–2.7%of control values) between the five groups. In contrast, PTCat the onset of reflex movement to carinal stimulation differed(7.4–17.0) between groups.     

Selective Electrothermolysis of the Sebaceous Glands: Treatment of Facial Seborrhea

BACKGROUND: There are few publications on facial seborrhea treatment. A focused therapy is needed. OBJECTIVE: Our aim was to evaluate the efficacy of electrothermolysis of the sebaceous glands. METHODS: In the preliminary studies, histologic changes in the cheek skin by electrothermolysis were examined by light microscopy. In the clinical studies, 15 adult women subjects with facial seborrhea were treated four times by the same procedure. A 1.50-mm-long needle with a 0.45-mm base insulation was inserted into pores in the forehead and cheeks, and a high-frequency electrical current was applied for 0.25 to 0.50 seconds with an output of 40 W. Each treatment took 60 to 90 minutes. The subjects returned for 6-months follow-up after their fourth treatment. RESULTS: Histology 1 and 6 months later showed fewer sebaceous glands and the development of fibrosis. All 12 subjects who completed the 6-month follow-up gave a subjective assessment of continuous reduction of facial seborrhea. On a scale of 0.0 to 3.0, the mean improvement score was 1.67+/-0.75. The mean reduction rate of skin surface lipids was 31.5% by sebumeter (p< .01). CONCLUSIONS: Even though this is a pilot, uncontrolled clinical assessment study, electrothermolysis of sebaceous glands may be an effective and safe approach for facial seborrhea treatment.     

Genetic susceptibility to type 2 diabetic nephropathy in human and animal models

SUMMARY:   Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) in Japan, Western Europe, and the United States. Mega studies such as Diabetes Control and Complication Trial (DCCT), Epidemiology of Diabetes Interventions and Complications (EDIC), and the United Kingdom Prospective Diabetes Study (UKPDS) clarified that poor glycemic and blood pressure control are undoubtedly involved in the development of nephropathy. However, these factors are not sufficient to predict which diabetic patients will develop renal disease, because not all patients with poor glycemic and blood pressure control develop renal disease. Since ethnic variations and familial clustering of diabetic nephropathy have been observed, genetic factors might contribute to susceptibility to this disease. Several methods such as (genome wide) association studies, sib-pair analysis, and quantitative trait loci (QTLs) analysis are available to examine polygenic diseases. However, no mutations that could explain the majority of nephropathy cases have been identified so far. The development of most diabetic nephropathy might be explained by the polygenic effect (i.e. many minor gene-gene interactions might be very important in the development of nephropathy). Identification of candidate genes of nephropathy enables targeting of therapy in patients at risk and development of novel therapeutic agents.     

Effects of Gadolinium Chloride on the Rat Lung Following Intratracheal Instillation

The metabolic behavior, clearance, and pulmonary effects ofgadolinium (Gd), one of the rare earth elements, were investigatedafter single intratracheal instillation of gadolinium chloride(GdCl₃) in male Wistar rats. There was a dose-related increasein Gd content of lung tissue. Gd content in the supernatantof bronchoalveolar lavage fluid (BALF) did not exceed 5 µgGd/ BALF even at a dose of 100 µg Gd/rat. Gd in the lungtissue decreased very slowly with a biological half-life of136 days at a dose of 50 µg Gd/rat. On the other hand,Gd content in the super natant of BALF was not detectable after31 days. These results suggest that intratracheally instilledGd can be retained in epithelial lining fluid only to a limitedextent as soluble forms and is deposited in the lung tissueprobably in insoluble forms which are metabolized very slowly.Calcium (Ca) content in BALF increased more rapidly than othertoxicological indices such as lactate dehydrogenase activity,protein concentration, and inflammatory cell counts. In thelung tissue, levels of Ca in Gd-instilled groups did not differfrom the control value. Although these data suggest that theorigin of Ca may be blood plasma, biological and/or toxicologicalsignificance of increased Ca is not known. The number of neutrophilsreached the maximum at 12 hr after instillation, indicatingthat Gd has the potency to cause acute lung toxicity. Summarizingthe observation, Gd instilled intratracheally into rats wasdeposited in the lung tissue in nonsoluble forms with an extremelylong half-life, while the metal caused a rapid and selectiveinfiltration of serum Ca before acute lung toxicity.     

Immunogenic Properties of Structurally Modified Human Tissue Plasminogen Activators in Chimpanzees and Mice

Immunogenic properties of second generation human tissue plasminogenactivator (tPA) derivatives were examined in chimpanzee andmouse systems. Five species of modified tPAs (mtPAs) (designated2660, 2663, 2810, 8000, and 9200), recombinant native tPA orbovine serum albumin (BSA) as a positive control were subcutaneouslyinjected nine times at suitable intervals into chimpanzees,genetically the closest species to man. These animals were testedfor antigen(Ag)-specific antibodies to the corresponding proteinsby means of enzyme-linked immunosorbent assay and Western blotanalysis. Neither 9200, one of the five mtPAs tested, nor tPAwas immunogenic, although BSA and the other four mtPAs wereimmunogenic under these conditions. Thus, an antigenic determinant was not exposed by the modification on 9200 and thismodified tPA is expected not to be immunogenic in humans. Inthe mouse studies, mice were immunized with mtPAs. Serum sam-piesfrom these animals were tested for antibodies to the mtPAs whichdid not concomitantly recognize native tPA by immune ad sorptionof the antibodies to tPA. The amount of such antibodies alterthe elimination of native tPA-reactive antibodies was littleor none when the serum samples from 9200 and from the othermtPAs, except 8000, were tested. Taking into consideration theresults of the chimpanzee studies, it can be concluded thatAg-specific antibodies are dominantly produced to unchangedepitopes present in modified proteins in the mouse system, inwhich the native protein is immunogenic. These results suggestthat the chimpanzee model should be useful to predict immunogenicityof second generation recombinant proteins in man, while themouse system adopted by us, which determines the newly generatedepitopes of the modified proteins, is not sufficient.     

Correlation between deletion patterns of SMN and NAIP genes and the clinical features of spinal muscular atrophy in Japanese patients

We conducted molecular analysis of two candidate genes for spinal muscular atrophy (SMA), the survival motor neuron gene (SMN) and the neuronal apoptosis inhibitory protein gene (NAIP), in 16 Japanese patients with SMA and compared the phenotypic features of SMA in these patients with the corresponding genotypes. Exons 7 and/or 8 of SMN were homozygously deleted in 11 SMA type I (Werdnig-Hoffmann disease) patients, two SMA type II patients and one SMA type III patient. Exons 5 and 6 of NAIP were homozygously deleted in six SMA type I patients. No patient had a deletion in NAIP without a deletion in SMN. Mechanical ventilation was required during the first 7 months of life in the SMA type I patients who had a deletion in both SMN and NAIP. Ventilatory support was initiated within 2 years after birth in patients who had a deletion in SMN but not in NAIP. We detected homozygous deletion of exon 5 of NAIP in the unaffected mothers of two SMA type I patients. In these families, the patients exhibited a deletion in both SMN and NAIP. The parents and unaffected siblings of these patients did not have a deletion in SMN. The present findings support the hypothesis that SMN deletion plays an important role in the development of SMA and suggest that combined deletion of both SMN and NAIP may be relevant for determining the disease severity.