The expected power of genome-wide linkage disequilibrium testing using single nucleotide polymorphism markers for detecting a low-frequency disease variant

The expected power of genome-wide linkage disequilibrium (LD) testing for a low-frequency disease variant was examined using a simple genetic model in which the degree of LD between the disease variant and the adjacent single nucleotide polymorphism (SNP) marker decreases in proportion to the number of generations since the LD-generating event. In this study, the frequency of the SNP marker being in complete LD with a low-frequency disease variant at the LD-generating event was regarded as the random variable having the probability distribution expected from the neutral infinite sites model, which enables us to derive the formula for calculating the expected power of genome-wide LD testing without determining the allele frequency of the associated SNP marker. Such a treatment is essential for the evaluation of the power of LD testing, because the frequency of the associated marker allele is always unknown. The main results obtained are as follows: (1) genome-wide LD testing with a case-control design could identify a disease variant with a high penetrance, while a low-frequency disease variant showing a low penetrance is difficult to detect; (2) although the degree of LD increases as the number of markers increases, the power of LD testing does not necessarily increase after the significance level is adjusted by the Šidák correction or the Bonferroni correction based on the number of testings; (3) the use of SNP markers with only high-frequency minor alleles is more powerful for detecting LD even with a low-frequency disease variant than the use of SNP markers with both high- and low-frequency minor alleles. Thus, the study design of LD testing must be evaluated prior to the investigation. The present study will provide a guideline for determining the number of SNP markers and the range of SNP allele frequencies suitable for genome-wide LD testing.     

Late-onset ornithine transcarbamylase deficiency in male patients: Prognostic factors and characteristics of plasma amino acid profile

BACKGROUND: The occurrence of male patients with ornithine transcarbamylase (OTC) deficiency during adolescence or in adulthood has now been recognized. The aim of this study was to determine the prognostic factors that affect the prognosis of life, to explore a basis for therapeutic strategy. METHODS: In 10 patients, nine of whom carried the R40H mutation and the other one carrying the Y55D mutation in the OTC gene, 32 demographic and laboratory data were first compared between survivors and non-survivors, using the unpaired t-test. The factors with significant difference were then subjected to multiple regression analysis. RESULTS: The factors that exhibited significant difference were: age at onset, concentration of plasma ammonium, blood pH, and concentrations of six amino acids in plasma. The multiple regression analysis then revealed concentrations of ammonium, leucine, lysine, isoleucine, phenylalanine, glutamine and proline to be significant prognostic factors. The amino acid profile in the 10 patients showed increases in glutamine, proline, lysine, valine and methionine, and decreases in serine, ornithine and arginine. There was an inverse correlation between the age at onset and the level of the residual hepatic OTC activity. CONCLUSION: The results implied that: (i) the plasma amino acid profile was unique, in comparison to other liver diseases; (ii) the plasma concentration of each of the (mentioned above) six amino acids was a significant predictor of prognosis; and (iii) suppression of protein catabolism, as suggested by the higher concentrations in isoleucine and leucine in the non-survivors, prevention of glutamine-induced brain edema, correction of alkalosis, and supplementation with ornithine or arginine may improve the prognosis of life.     

Angiomyolipoma of kidney involving the inferior vena cava

We successfully treated a case of angiomyolipoma of the right kidney involving the inferior vena cava. Tissue sections of the tumor were immunostained and immunohistochemically tested with the smooth muscle related antibodies, namely, calponin h1, h-caldesmon and alpha-smooth muscle actin, and were then compared with the five cases of common type of angiomyolipoma. Furthermore, we reviewed and analyzed 25 case reports of invasive renal angiomyolipomas.     

Interstitial pneumonitis related to flutamide monotherapy for prostate cancer

A 88-year-old man with prostate cancer was receiving non-steroidal anti-androgen therapy (flutamide, 375 mg/day). Three weeks after starting therapy, the patient developed dyspnea and bilateral pulmonary interstitial infiltrates. The withdrawal of flutamide and the initiation of steroid therapy resulted in clinical improvement.     

Radiologic and Endoscopic Documentation of Improvement of Gastric Cancer by Chemotherapy: A Case Report

A case of gastric cancer is reported, in which chemotherapyshowed a marked effect and the responses were clearly documentedradiologically and endoscopically. The patient was a 71-year-old male with angina pectoris. Henoticed epigastric pain in October 1978. Subsequent radiologicand endoscopic examinations revealed advanced cancer just belowthe gastric cardia. He was treated with N-(2-tetrahydrofuryl)-5-fluorouraciland mitomycin C instead of surgery. Marked improvement was shownabout five months after the initiation of chemotherapy. At thesame time gastric biopsy no longer revealed cancer cells. Thepatient is living and well at this writing.     

Risk factors in past histories and familial episodes related to development of testicular germ cell tumor

BACKGROUND: A retrospective study was conducted to examine the host factors of 240 testicular germ cell tumor patients. This study was performed to address a new theory proposed by Skakkebaek called testicular dysgenesis syndrome which claims that cryptorchism, hypospadias, poor semen quality and testicular germ cell tumors are symptoms of an underlying testicular dysgenesis in uterus. METHODS: The past health histories and familial episodes of 240 testicular germ cell tumor patients were examined. The past health histories included cryptorchism, hypospadias, infertility, atrophic testis and inguinal hernia. RESULTS: Of the 240 patients, 13 (5.4%) had a history of cryptorchism or orchidopexy. Two (0.8%) showed existence of hypospadias or had experienced urethroplasty. Among 129 married couples, 104 (80.6%) couples were fertile. Three (1.3%) patients developed testicular tumors after they were diagnosed as infertile or came to the hospital with the complaints of infertility. Four (1.7%) had contralateral atrophic testis. 19 (7.9%) had experienced inguinal herniorrhaphy before age 15. Three (1.3%) had testicular germ cell tumor patients among their family or relatives. CONCLUSIONS: The testicular germ cell tumor patients showed a considerable incidence of complications such as cryptorchism, hypospadias and incomplete closure of processus vaginalis. Cryptorchism, perinatal factors and familial factors could be risks for developing testicular germ cell tumors.     

Liaison psychiatry and HIV infection (II): Application of relaxation in HIV positive patients

Abstract We examined the efficacy of relaxation techniques in a sample of HIV patients without AIDS in the early stages after infection, by comparing the three groups: relaxation group (progressive muscle relaxation and modified autogenic training); ordinary supportive psychotherapy group, and finally no psychiatric treatment group. Scores for anxiety, fatigue, depression and confusion , as measured by the profile of mood states (POMS), were significantly lower after relaxation than before. There were no significant differences in the POMS scores (except for anger ) among the three groups. These two results suggest that a combination of progressive muscle relaxation and modified autogenic training is a useful method, which can be easily employed in HIV patients without AIDS.     

In-vivo Microdialysis Study of the Distribution of Cisplatin into Brain Tumour Tissue after Intracarotid Infusion in Rats With 9L Malignant Glioma

Simultaneous brain microdialysis in tumour and non-tumour tissues has been used for kinetic determination of the local distribution of an anticancer agent, cisplatin, in rats. Rat brain was implanted with 9L malignant glioma and cisplatin (3.5 mg kg^?) was administered as a selective intracarotid infusion for 30 min to rats prepared for brain microdialysis. The amount of platinum in the dialysate collected from tumour and non-tumour brain tissues was determined by atomic absorption spectrophotometry, as representative of cisplatin. Total and free platinum concentrations in plasma were also measured. Free platinum is accumulated preferentially in the tumour tissue and the brain tumour distribution coefficient (the ratio of brain tumour platinum AUC to plasma free platinum AUC, where AUC is the area under the platinum concentration-time curve) was 0.69, although there was little distribution into normal brain tissue. Drug binding to plasma proteins was 65%. It is concluded that simultaneous microdialysis is an easy and available method for assessing in-vivo local pharmacokinetics and distribution of cisplatin in tumour and non-tumour tissues of the brain.     

Epidemiology of inflammatory neurological and inflammatory neuromuscular diseases in Tottori Prefecture, Japan

Abstract We investigated the incidence of the following conditions: inflammatory neurological and neuromuscular diseases, adult meningitis and adult encephalitis in Yonago City, and Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), polymyositis/dermatomyositis (PM/DM), periarteritis nodosa (PN) and HTLV-1 associated myelopathy (HAM) during the period 1988–1992 in Tottori Prefecture, Japan. The annual incidence per 100 000 population was as follows: meningitis, 4.38; encephalitis, 0.90; GBS, 1.14; PM/DM, 1.01; and PN, 0.32. The prevalence per 100 000 population CIDP, 0.81; PM/DM, 9.92; PN, 2.59; and HAM, 1.30. There was marked localization of HAM in western Tottori, and there was seasonal variation in the prevalence of meningitis, encephalitis and GBS. The mean age at onset of meningitis was lower than that for encephalitis. Comparison with reported data revealed interracial differences in the epidemiology of PM/DM and PN.     

Endoscopic Diagnosis of Colorectal Villous Adenoma

Villous adenoma or adenoma with a predominant villous componentshowed a characteristic finding on macroscopic or endoscopicobservation. The fundamental elements which constitute thisfinding were reddish sulcus and whitish ramified relief similarto the villous pattern normally seen on the mucosa of the smallbowel. We called this feature "V (villous) pattern." A comparativestudy of the endoscopy and pathology of 70 polypoid lesionsof the large intestine was conducted, with the following results:The frequency of the V pattern in the endoscopic picture increasedin proportion to the population of the villous component inhistological picture of the polypoid lesions. However, evenin small polyps the V pattern could be observed when the lesionhad a villous component. Careful and close endoscopic observationmay allow the diagnosis of villous component (which means ahigh frequency of malignancy) of the colorectal polyp even withoutbiopsy. Dr. Makino's present address: Av. Ceará, 335, Belém—Pará,Brasil.