Inhibition of cellular mediated immunity in marihuana smokers.

The cellular mediated immunity of 51 young chronic marihuana smokers. as evaluated by the lyomphocyte response in vitro to allogeneic cells and to phytohemagglutinin, was significantly decreased and similar to that of patients in whom impairment of T (thymus derived) cell immunity is known to occur. This inhibition of blastogenesis might be related to an impairment of DNA synthesis.

[Preservation of aortic root with severe destruction in Stanford type A acute aortic dissection].

From November 1999 to December 2008, 197 patients with Stanford type A acute aortic dissection underwent the surgical treatment on an emergency basis. In 19 cases, we preserved the severely destroyed aortic root using gelatin-resorcin-formalin (GRF) glue avoiding aortic root replacement. We examined the indication and limitation of repair of the destroyed aortic root. The 19 patients were classified into 3 groups (A, B and C). Group A consisted of 7 patients who had no aortic regurgitation (AR). Group B consisted of 6 patients who had moderate to severe AR. Group C consisted of 6 patients who had coronary involvement. We preserved the broken aortic root in group A and group B. But it seemed to be rather difficult to repair the destroyed aortic root in some cases of group C.

[Coronary artery aneurysm with various clinical course].

Case 1: A 77-year-old woman had effort angina pectoris. Coronary angiography (CAG) revealed a coronary artery aneurysm on the left descending artery. Coronary artery bypass grafting (CABG) and patch angioplasty for the aneurysm were performed. Case 2 : A 69-year-old woman had effort dyspnea CAG showed dilation of the left main trunk and beaded aneurysms (maximum 6 cm in diameter) behind the ascending aorta with a fistula to the right atrium. We closed the fistula and performed CABG to the circumflex branch. Case 3 : A 78-year-old woman had had general fatigue for 2 weeks. Previous CAG had revealed coronary artery aneurysms and current chest computered tomography revealed pericardial effusion. She was, therefore, diagnosed with the rupture of the coronary artery aneurysm. We closed the coronary artery aneurysm and performed CABG. Case 4: A 55-year-old man had been diagnosed with acute myocardial infarction and had undergone percutaneous coronary intervention 3 years before. CAG revealed a coronary artery aneurysm on the right coronary artery. We resected the aneurysm and interposed with saphenous vein graft. Although coronary artery aneurysm often has no symptoms, in the cases of angina, myocardial infarction, rupture or large aneurysm more than 3 times larger than the normal diameter, surgical repair should be considered.

[Surgical treatment for acute type A aortic dissection; for better postoperative quality of life].

From November 1999 to December in 2005, 114 patients with acute type A aortic dissection underwent surgical treatment on an emergency basis. The overall in-hospital mortality was 7.9% (9 patients). Four were rupture cases before cardiopulmonary bypass. De novo postoperative stroke rate was 3.5% (4 patients). But all of them were discharged on foot. There were 6 rupture cases before operation. Unfortunately only 2 patients survived. Preoperative stroke due to malperfusion occurred in 19 cases (16.7%). Among them, those with clear consciousness had tendency to better social rehabilitation than those with drowsiness. We had experienced 2 vegetable states in the group of drowsiness after the operations. For better outcome, we must avoid rupture before operation and reconsider the timing of operation in the case of brain ischemia.

Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens.

The aromatase enzyme complex catalyzes the conversion of androgens to estrogens in a wide variety of tissues, including the ovary, testis, placenta, brain, and adipose tissue. Only a single human gene encoding aromatase P450 (CYP19) has been isolated; tissue-specific regulation is controlled in part by alternative promoters in a tissue-specific manner. We report a novel mutation in the CYP19 gene in a sister and brother. The 28-yr-old XX proband, followed since infancy, exhibited the cardinal features of the aromatase deficiency syndrome as recently defined. She had nonadrenal female pseudohermaphrodism at birth and underwent repair of the external genitalia, including a clitorectomy. At the age of puberty, she developed progressive signs of virilization, pubertal failure with no signs of estrogen action, hypergonadotropic hypogonadism, polycystic ovaries on pelvic sonography, and tall stature. The basal concentrations of plasma testosterone, androstenedione, and 17-hydroxyprogesterone were elevated, whereas plasma estradiol was low. Cyst fluid from the polycystic ovaries had a strikingly abnormal ratio of androstenedione and testosterone to estradiol and estrone. Hormone replacement therapy led to breast development, menses, resolution of ovarian cysts, and suppression of the elevated FSH and LH values. Her adult height is 177.6 cm (+2.5 SD). Her only sibling, an XY male, was studied at 24 yr of age. During both pregnancies, the mother exhibited signs of progressive virilization that regressed postpartum. The height of the brother was 204 cm (+3.7 SD) with eunuchoid skeletal proportions, and the weight was 135.1 kg (+2.1 SD). He was sexually fully mature and had macroorchidism. The plasma concentrations of testosterone (2015 ng/dL), 5 alpha-dihydrotestosterone (125 ng/dL), and androstenedione (335 ng/dL) were elevated; estradiol and estrone levels were less than 7 pg/mL. Plasma FSH and LH concentrations were more than 3 times the mean value. Plasma PRL was low; serum insulin-like growth factor I and GH-binding protein were normal. The bone age was 14 yr at a chronological age of 24 3/12 yr. Striking osteopenia was noted at the wrist. Bone mineral densitometric indexes of the lumbar spine (cancellous bone) and distal radius (cortical bone) were consistent with osteoporosis; the distal radius was -4.7 SD below the mean value for age- and sex-matched normal men; indexes of bone turnover were increased. Hyperinsulinemia, increased serum total and low density lipoprotein cholesterol, and triglycerides and decreased high density lipoprotein cholesterol were detected.(ABSTRACT TRUNCATED AT 400 WORDS)

Molecular and epidemiological studies of Werner syndrome in the Japanese population.

Werner syndrome (WS) is an autosomal recessive genetic disease characterized by many age-related features. The gene responsible for WS (WRN) has been isolated and contains a helicase domain, but its function is unknown. Six different mutations throughout the WRN gene have been reported in the Japanese population. We have studied whether patients with a specific mutation exhibit distinct phenotypes from others. Fourteen patients with different mutations showed almost the same signs and symptoms and, therefore, the C terminal part of the product appears to be crucial for its functions, although other parts may be important as well. Haplotype analyses using 13 microsatellites covering the 2.8-3.0 cM WRN region showed that two out of six different mutations had founder chromosomes. These two founder chromosomes may be evenly distributed throughout the western part of Japan, suggesting that these mutations go back to a time earlier than 1400 years ago.

Transcriptional activation by the Werner syndrome gene product in yeast.

Werner syndrome (WS) is characterized by the premature occurrence of many age-related features. Before the cloning of the gene for WS (WRN), several reports suggested that transcriptional defects of genes may relate to the mechanisms of the occurrence of WS and natural aging. Because WRN, which encodes a helicase (WRN-H), has been cloned, we are attempting to clarify the mechanism of the transcriptional abnormalities found in WS cells, using WRN and WRN-H. In this article, we studied transcriptional activation of a promoter by WRN-H in a yeast assay system as a first step. The results showed that WRN-H functions as a transcriptional activator in the system. Furthermore, we performed additional transcriptional assays using various parts of WRN to define the critical region of WRN-H for transcriptional activation in yeast. The results revealed the critical region for the activation most likely mapped to the region of 315 to 403 aa. The region of 404 to 1309 aa may also effect activation in the presence of the critical region. The two regions contain an acidic domain, and the region of 404 to 1309 aa also contains a helicase domain. If this transcriptional activation by WRN-H occurs also in human cells in vivo, direct activation of the promoters by WRN-H could explain the results of somatic cell hybrid studies as well as the overexpressed genes detected in WS cells. However, our results should be interpreted with caution, because thus far, the transcriptional activation by WRN-H were only demonstrated using one promoter in a yeast system.

Are adolescent suicide attempters noncompliant with outpatient care?

The outpatient clinic attendance patterns of 115 consecutively referred 10- to 18-year-old suicide attempters and of 110 nonattempters were compared. The two groups did not differ in number of appointments scheduled or missed, but attempters kept significantly fewer appointments than did nonattempters. Seventy-seven percent of each group dropped out of treatment, but attempters dropped out significantly faster. Attendance and dropout were unrelated to age, reason for referral, or previous attempts. Girls missed more appointments than did boys, and Hispanic patients kept a smaller percentage of scheduled appointments than did other ethnic groups. We conclude that adolescent attempters are not more likely to drop out of treatment but keep fewer appointments and remain in care more briefly than do other outpatients. Recommendations for triage and brief case management are made.

Syndrome of septo-optic-pituitary dysplasia: the clinical spectrum.

Septo-optic-pituitary dysplasia is a syndrome characterized by abnormalities of midline brain structures, optic nerve hypoplasia, and congenital hypothalamic-pituitary insufficiency. Four infants, diagnosed as having clinical variations of this disorder, are described. The first had agenesis of the septum pellucidum and corpus callosum, partial hypothalamic insufficiency, and normal optic nerves. The second had a structurally normal brain, bilateral optic nerve hypoplasia, and panhypopituitarism. The third had bilateral agenesis of the cerebral cortex, bilateral optic nerve hypoplasia and partial hypothalamic insufficiency. The fourth had a structurally normal brain, unilateral optic nerve hypoplasia and panhypopituitarism. A review of the recent literature revealed 191 patients with bilateral optic nerve hypoplasia who were examined for possible existence of this syndrome. Of the 178 patients who had radiographic imaging of the brain, 60% were found to have structural abnormalities. Of the 145 patients evaluated for pituitary function, 62% had evidence of insufficiency. Approximately 30% of fully evaluated patients had evidence of all three components of the syndrome. Because of high incidence of structural abnormalities of the brain and congenital hypopituitarism in patients with optic nerve hypoplasia, we conclude that full evaluation is indicated in patients with any of the three components of the syndrome.

The effect of medroxyprogesterone acetate on gonadotropin secretion in girls with precocious puberty.

Plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) as detected by radioimmunoassay have been found to be present in prepubertal children and show a gradual rise until the onset of puberty. Children with idiopathic true precocious puberty have plasma gonadotropin levels which are appropriate for their advanced degree of sexual development. A potent progestational agent, 6-methyl-17-hydroxyprogesterone acetate or medroxyprogesterone has been used in the treatment of precocious puberty and will suppress its physical manifestations. In this study the effect of medroxyprogesterone on gonadotropin levels was investigated in seven girls with true precocious puberty. Plasma LH values were found to be significant lower in patients receiving this agent than in a group of normal prepubertal girls. FSH values did not differ from the control group. One patient was evaluated prior to treatment and showed decreasing levels of LH after therapy was begun. These data suggest that medroxyprogesterone may act on the pituitary-hypothalamic axis to suppress the pubertal levels of LH.

PIP: Plasma LH (luteinizing hormone) and FSH (follicle stimulating hormone) have been detected by radioimmunoassay in prepubertal children and show a gradual rise until the onset of puberty. Children with precocious puberty have plasma gonadotropin levels appropriate for their advanced sexual development. A clinical study was undertaken to determine whether Depo-Provera administered to girls in precocious puberty would have an effect on the serum gonadotropin levels. 7 girls aged 5-10 who manifested signs of prococious puberty were treated with Depo Provera and compared with 15 normal 5-10-year old girls. The Depo Provera succeeded in lowering plasma LH levels significantly below those in normal prepubertal girls. The Depo Provera had no effect on FSH levels. The mechanism whereby Depo Provera decreases LH levels is unclear. It is possible that it affects the hypothalamic releasing factor. Another explanation is that it may act as a nonspecific pituitary suppressor or may inhibit the rise in LH which seems to occur during sleep in normal pubertal children.

Cognitive ability and everyday functioning in women with Turner syndrome.

This paper presents results from an assessment of cognitive ability and everyday functioning in a group of adult women with Turner syndrome (TUS). Twenty-three TUS women were compared with 23 matched controls with constitutional short stature (CSS). A subgroup of 10 TUS women were compared with their nondisabled female siblings. On the Wechsler Adult Intelligence Test-Revised (Wechsler, 1981), no significant group differences were found in Verbal IQ. There were significant group differences for Performance IQ and Full Scale IQ, largely due to specific deficits in the area of spatial and mathematical ability. These difficulties were also evident on the Benton Visual Retention Test-Revised (Benton, 1974). TUS individuals had significantly lower educational attainment than CSS controls but did not differ from their siblings. TUS individuals had significantly lower occupational attainment than the women in both comparison groups.

[Genetic analysis of Werner syndrome in a family].

Werner syndrome (WRN) is a rare autosomal recessive disorder, one of the progeroid syndromes, and is characterized by features of premature aging. The incidence of WRN in the Japanese population, 1 in 200,000, is higher than than that in the Caucasian population. The genetic defect of WRN is unknown. But genetic linkage to several markers on the short arm of chromosome 8 has been reported recently. Here, we studied one family with WRN in which an affected individual had a papillary thyroid carcinoma and myelodysplastic syndrome. Using 4 microsatellites closely located to the WRN locus: D8S360, D8S1055, D8S339 and ANK1, we analyzed the genotypes of this patient, her three siblings and her parents, who were first cousins. The mutative haplotype, identified through the generations in pedigree, helps detect a carrier or a presymptomatic patient. The eldest sister inherited two normal haplotypes, but the second sister inherited one mutative haplotype. There was no difference in clinical signs and symptoms between these sisters. when the WRN gene is isolated, it will help us understand the mechanism of aging.

[A case of mild-type myotonic dystrophy with dementia and severe arteriosclerosis obliterans].

A 70-year-old man, with mild-type myotonic dystrophy (MyD) diagnosed by molecular genetic analysis when he was 68 years old, complained of worsening intermittent claudication during the past 2 years. Doppler examination revealed severe stenosis and obstruction in his leg arteries, which we diagnosed as arteriosclerosis obliterans (ASO). We then found him to be suffering from dementia, which was confirmed by dementia scale tests (Mini Mental State, 20/30; Hasegawas' Dementia Scale-Revision, 15/30). Even in mild-type MyD, as MyD is one of the progeria syndromes, the abnormal genes of MyD may accelerate the aging processes.