Analysis of cases of central nervous system fungal infections reported in Japan between January 1979 and June 1989.

Data from 129 cases of central nervous systemic fungal infections reported in Japan between January 1979 and June 1989 were analyzed. Of 129 cases, 116 were cryptococcal meningitis, 6 candidal meningitis (including meningitis due to Trichosporon cutaneum) and 7 Aspergillus meningoencephalitis. Fifty-six of the patients with cryptococcal meningitis had an underlying systemic disease or condition. The overall survival rate was 72.4%, which was a markedly improved rate compared to earlier reports. Cryptococcal meningitis was treated most often with the combination of intravenous amphotericin B and 5-fluorocytosine and was associated with a survival rate of 81.8%. All 7 patients treated with fluconazole alone survived. Candidal meningitis occurred secondary to a shunt infection; some patients with candidemia did well when adequate therapy was instituted. Aspergillus meningoencephalitis is most often diagnosed at autopsy or in surgical specimens and the prognosis of Aspergillus meningoencephalitis is generally poor.     

Cellularity and Adipogenic Profile of the Abdominal Subcutaneous Adipose Tissue From Obese Adolescents: Association With Insulin Resistance and Hepatic Steatosis

OBJECTIVE

We explored whether the distribution of adipose cell size, the estimated total number of adipose cells, and the expression of adipogenic genes in subcutaneous adipose tissue are linked to the phenotype of high visceral and low subcutaneous fat depots in obese adolescents.

RESEARCH DESIGN AND METHODS

A total of 38 adolescents with similar degrees of obesity agreed to have a subcutaneous periumbilical adipose tissue biopsy, in addition to metabolic (oral glucose tolerance test and hyperinsulinemic euglycemic clamp) and imaging studies (MRI, DEXA, ¹H-NMR). Subcutaneous periumbilical adipose cell-size distribution and the estimated total number of subcutaneous adipose cells were obtained from tissue biopsy samples fixed in osmium tetroxide and analyzed by Beckman Coulter Multisizer. The adipogenic capacity was measured by Affymetrix GeneChip and quantitative RT-PCR.

RESULTS

Subjects were divided into two groups: high versus low ratio of visceral to visceral + subcutaneous fat (VAT/[VAT+SAT]). The cell-size distribution curves were significantly different between the high and low VAT/(VAT+SAT) groups, even after adjusting for age, sex, and ethnicity (MANOVA P = 0.035). Surprisingly, the fraction of large adipocytes was significantly lower (P < 0.01) in the group with high VAT/(VAT+SAT), along with the estimated total number of large adipose cells (P < 0.05), while the mean diameter was increased (P < 0.01). From the microarray analyses emerged a lower expression of lipogenesis/adipogenesis markers (sterol regulatory element binding protein-1, acetyl-CoA carboxylase, fatty acid synthase) in the group with high VAT/(VAT+SAT), which was confirmed by RT-PCR.

CONCLUSIONS

A reduced lipo-/adipogenic capacity, fraction, and estimated number of large subcutaneous adipocytes may contribute to the abnormal distribution of abdominal fat and hepatic steatosis, as well as to insulin resistance in obese adolescents.White adipose tissue (WAT) plays a critical role in obesity-related metabolic dysfunctions. Danforth (1) and Shulman (2) raised the hypothesis that inadequate subcutaneous fat stores result in lipid overflow into visceral fat and other nonadipose tissues, which was elegantly explored by Ravussin and Smith (3). Sethi and Vidal-Puig proposed that impaired subcutaneous WAT expandability might cause obesity-associated insulin resistance (4). In adults, increased fat cell size, a marker of impaired adipogenesis, was reported to be related to insulin resistance and predicts the development of type 2 diabetes (5). Recent studies by McLaughlin et al. (6) reported in adults that an increase in the proportion of small adipocytes, but not increased fat cell size, and an impaired expression of markers for adipogenesis are related to insulin resistance. Little is known about adipocyte size and adipogenic capacity during adolescence, a time when the expansion of WAT results from combined adipocyte hypertrophy and hyperplasia. In contrast, adult adipocytes exhibit a remarkably constant turnover (7). Recently, we described a group of obese adolescents presenting with a reduced subcutaneous abdominal fat depot, increased visceral fat, hepatic steatosis, and marked insulin resistance (8). Building on these findings, we asked the following question: is the adipogenic capacity of the abdominal subcutaneous fat depot in obese adolescents associated with a decreased proportion of large adipose cells and reduced expression of genes regulating adipocyte differentiation? We hypothesized that, in some obese adolescents, the lack of expandability of the subcutaneous abdominal fat might be linked to adipocyte size, its adipogenic expression, and the fat accumulation in liver and muscle. To test this hypothesis, we used metabolic and imaging techniques, together with direct measurements of adipocyte size and gene expression, in two groups of obese adolescents with marked differences in the proportion of visceral to subcutaneous abdominal fat.     

Plasma amitriptyline level after acute administration, and driving performance in healthy volunteers

Aims: Amitriptyline triggers the impairment of cognitive and motor functions and has been confirmed to have harmful effects on driving performance. Although interindividual differences in plasma concentration may cause variations in driving performance, the relationship between plasma amitriptyline concentration and its effect on driving performance has not been completely elucidated. Thus, the aim of the present study was to assess the influence of individual pharmacokinetic differences on driving performance and cognitive functions. Methods: In this double‐blinded study, 17 healthy male volunteers were given an acute, single, 25‐mg dose of amitriptyline. The subjects were assigned three driving simulator tasks, three cognitive tasks, and the questionnaire of the Stanford Sleepiness Scale at the baseline and at 4 h after dosing. The plasma amitriptyline concentrations were measured on high‐performance liquid chromatography. Results: A significant positive correlation was observed between the plasma amitriptyline concentration and road‐tracking performance (r = 0.543, P < 0.05). There was no significant correlation between the plasma amitriptyline concentration and other driving performance, cognitive functions, and subjective somnolence. Conclusions: Amitriptyline produces a concentration‐related impairment on road‐tracking performance. Therapeutic monitoring of amitriptyline would be useful for predicting the difficulties involved while driving.     

Temporal and spatial localization of three germline-specific proteins in medaka.

We show that germline-specific proteins, olvas (vasa), nanos, and tdrd1 (tudor), alter their localization in the cytoplasm during germline development in the medaka (Oryzias latipes). By immunohistochemical analysis, these three germline-specific proteins were detectable on granule-like structures in the cytoplasm of migrating primordial germ cells. In the germ cells of the gonadal primordia, these granules formed a hollow area lacking these three protein components. During the sexual differentiation of the female gonads, the granules were found to be reduced in size in the germ cells undergoing cystic division and they showed a perinuclear localization in the oocytes. However, the germ cells in the male gonads retained their hollow granules during this early sex differentiation stage. We further demonstrate the differential localization of olvas, nanos, and tdrd1 on these granules during medaka germline development.     

A study on the effect of combined chemotherapy on Mycobacterium avium complex pulmonary disease

Annual incidence of Mycobacterium avium complex (MAC) pulmonary disease has been gradually increasing in the last 10 years in Japan, however, the optimal therapeutic regimen for the disease has not yet established. We investigated the effect of our new regimen in twenty seven cases of pulmonary MAC infection without HIV infection, diagnosed according to the American Thoracic Society criteria during the period from January 1996 to October 1997 at our hospital. These patients were treated with rifampicin (RFP), ethambutol (EB) and clarithromycin (CAM) for more than 12 months, together with streptomycin (SM) initially (first 2-3 months), except one patient who was treated for 11 months only. Twenty-four months after the therapy, sputum cultures converted from positive to negative in 13 patients and the amount of bacilli in sputum reduced in two patients. The radiological findings improved in 10 patients, showed no significant changes in 11 patients, while worsened in the remaining 6 patients. As to adverse reactions 1 case of liver damage, 3 cases of skin disorders, 4 cases of gastrointestinal malfunctions, and 1 case of optic neuritis were observed. This regimen was safe and tolerable even in the elderly outpatients, but not so effective against MAC pulmonary disease compared with the results of recent reports from the U.S. and Europe. Size of pulmonary lesions was closely associated with the effectiveness in this study. However, five bacteriologically converted cases did not show radiological improvement, and the reasons behind this fact remain to be investigated.