Nuclear spheroids in neurons of the human hypothalamus]

Morphological structure, distribution and frequency of the so-called "nuclear spheroids" have been studied in the human hypothalamus. The following results were obtained: 1. By light microscopy, the nuclear spheroids turned out to be small or large spheroid bodies inside the nucleus. They are almost homogeneous, rarely granular, vacuolar or reticular and occasionally they are multiple. They are best stained with the cresyl-violet technique. They do not exhibit any histochemical pecularities. Aside from typical nuclear spheroids, irregularly shaped nuclei were frequently seen, associated with increased nuclear folds, transitional stages between nuclear folds and nuclear spheroids were also present. Certain microscopic features suggest invagination and displacement of nuclear membrane and cytoplasm into the karyoplasma. 2. By electron microscopy, the nuclear spheroids consist of nuclear membranes and cytoplasmic constituents. They, therefore, actually represent cytoplasm protruding into the cell nucleus. 3. The nuclear spheroids occur almost regularly and most frequently in the ventromedial field of the tuber cinereum, foremost in the infundibular (= arcuate) nucleus. They numerically increase during life. They are rarely found in the ventromedial nucleus but do occur in most of the adults. In the paraventricular nucleus, the supraoptic nucleus, the lateral nuclei tuberis, and in lateral hypothalamic nucleus, they are found by far less often. They scarcely develop in the preoptic area, in the dorsal field, in the tubero-mamillar complex, in the parafornical nuclear groups, in the premamillary nucleus and in the mamillary nuclei. 4. Within the infundibular (= arcuate) nucleus, the nuclear spheroids are particularly numerous in the basal and basolateral regions, whose neurons, under certain functional conditions--such as the Sheedan syndrome, in the menopause and in association with pituitary neoplasms-, appear hypertrophic. Within the hypertrophic neurons of this region, which we designate the subventricular part of the infundibular nucleus, nuclear spheroids are definitely more frequent, and they are of the large type. 5. A separation of the subventricular part based on the distributional pattern of the nuclear spheroids indicates a pathological karyoarchitectonics which supplements the normal karyoarchitectonics (Bachmann, 1948). 6. The nuclear spheroids seem to be associated with increased neuronal activities, for their frequently strongly correlates with the neuronal hypertrophy which expresses enhanced neuroendocrinological activity.     

Primary pleomorphic adenoma in posterior cranial fossa

A 35-year-old woman had an intradural tumor in the posterior fossa adjacent to the posterior wall of the left pyramidal bone, which was totally removed and histologically diagnosed as a pleomorphic adenoma. Follow-up examination for 2 years showed no recurrence of the tumor. There was no primary lesion in any other gland of the body, and therefore there is no alternative but to conclude a “migration” of some gland cells. The pathogenesis of this tumor remains unclassified.     

Relevance of a New Impedance Matching, or Subtrap, Method for the Reduction of Pain During Hyperthermia

Capacitive heating is widely used in hyperthermic treatment of human malignancies. However, the pain on the body surface or thermoesthesia in the subcutaneous fatty layer may prevent an elevation of temperature in the tumors. Impedance matching is improved by a subtrap method entailing the application of two copper plates (10×850×0.06 mm) as a subtrap circuit to each of two capacitive electrodes. In a clinical trial the Tmax, Tave, Tmin for the subtrap method were all higher in comparison with those for the conventional technique (42.5±0.7°C, 41.9±1.0°C, 41.3±1.1°C vs. 41.1±1.5°C, 40.6±1.3°C, 40.0±1.3°C). Although the maximal radiofrequency (RF) power applied to patients was higher with the subtrap method (875±189 W vs. 763±200 W), the incidence of surface pain was reduced dramatically. It is concluded that the subtrap method substantially improves the RF capacitive heating of deep-seated tumors.     

The influence of human T lymphotropic virus type I infection on the outcome of cardiovascular surgery

OBJECTIVE: Human T lymphotropic virus type I infects CD4(+) T cells and affects cell-mediated immunity. Cardiopulmonary bypass transiently alters lymphocyte subsets, resulting in a reduction in CD4(+) T cells and an increase in CD8(+) T cells. We proposed that cardiovascular operations and human T lymphotropic virus type I infection may act synergistically, resulting in serious damage to cell-mediated immunity. METHODS: A total of 517 consecutive patients who were preoperatively screened for anti-human T lymphotropic virus type I antibody and underwent cardiovascular operations with cardiopulmonary bypass were enrolled in this study. Of the 517 patients, 82 (16%) had positive test results for anti-human T lymphotropic virus type I antibody. The surgical outcome of patients with positive and negative results for anti-human T lymphotropic virus type I antibody was analyzed retrospectively. RESULTS: There was no difference between the 2 groups with respect to early mortality. Distribution of survival curve was also not significantly different (P =.5; mean follow-up duration, 2.4 +/- 1.8 years [range, 0-9.4 years] and 3.2 +/- 2.8 years [range, 0-9.8 years]) in the groups with positive and negative antibody results, respectively). In particular, long-term follow-up did not reveal adult T-cell leukemia or human T lymphotropic virus type I-associated myelopathy, and occurrence of neoplasm did not differ between groups. Early infectious complication was, however, significantly higher in the group with positive antibody results than in the group with negative results (P =.02). Logistic regression analysis revealed human T lymphotropic virus type I infection as a significant risk for this complication (P =.04; odds ratio, 2.5; 95% confidence interval, 1. 0-5.8). CONCLUSION: A combination of human T lymphotropic virus type I infection and cardiovascular operation is believed to increase the potential risk of infectious complications shortly after the operation. However, this synergistic effect seems to be transient and has little influence on long-term prognosis.     

No Improvement of Adult Height in Non-growth Hormone (GH) Deficient Short Children with GH Treatment

It is still in doubt whether the standard-dose growth hormone (GH) used in Japan (0.5 IU/kg/week, 0.167 mg/kg/week) for growth hormone deficiency is effective for achieving significant adult height improvement in non-growth hormone deficient (non-GHD) short children. We compared the growth of GH-treated non-GHD short children with that of untreated short children to examine the effect of standard-dose GH treatment on non-GHD short children. GH treatment with recombinant human growth hormone (rhGH) was started before the age of 11 yr in 64 boys and 76 girls with non-GHD short stature registered at the Foundation for Growth Science who have now reached their adult height. In 119 untreated boys and 127 untreated girls whose height standard deviation score (SDS) was below –2 SD at the age of 6 yr, height growth was followed until 17 yr. Height SDS was significantly lower before GH treatment in the GH-treated group than at the age of 6 yr in the untreated group, in both sexes. Adult height and adult height SDS were significantly greater in the untreated group than in the GH-treated group, in both sexes, although the change in height SDS did not differ significantly. Height SDS was significantly lower before GH treatment in the GH-treated group than at the age of 6 yr in the untreated group, so 57 boys and 57 girls whose height SDS at the age of 6 yr in the untreated group closely matched the height SDS before GH treatment in the GH-treated group were chosen for comparison. Height SDS did not differ significantly between the GH-treated group before GH treatment and the untreated group at the age of 6 yr, nor were there differences between these subgroups in adult height, adult height SDS, or height SDS change, in either sex. The effect of GH treatment is reported to be dose-dependent and doses over 0.23 mg/kg/week are reported to be necessary to improve adult height in non-GHD short children. Currently, the GH dose is fixed at 0.175 mg/kg/week in Japan, and we expected to find, and indeed concluded, that ordinary GH treatment in Japanese, non-GHD short children does not improve adult height.     

Differences in hemodynamic effects of amrinone, milrinone and olprinon after cardiopulmonary bypass in valvular cardiac surgery

The differences in hemodynamic effects of amrinone, milrinone and olprinone were evaluated in 46 patients for valvular cardiac surgery after cardiopulmonary bypass (CPB). Patients were randomly allocated to three groups; group A with amrinone infusion (17 patients); group M with milrinone infusion (15 patients); and group O with olprinone infusion (14 patients). Each drug was administrated as a single dose into the venous reservoir of the CPB circuit 15 min prior to the end of emergence from CPB, followed by continuous infusion. Hemodynamic parameters were measured at the time of preCPB (C0), just after the end of CPB (C1), one hour after the termination of CPB (C2) and after the chest closure (C3). Catecholamines were used in order of dopamine, norepinephrine and dobutamine. These doses were modulated to maintain the cardiac index > 3.0 l.min-1.m-2 by each anesthesiologist. Hemodynamic parameters (at C0, C1, C2 and C3) and the doses of cathecholamine (at C1, C2 and C3) were compared among the 3 drugs. The systolic blood pressure in group M was significantly higher than that of group A and group O after chest closure. In group M and A, the systolic blood pressure showed a significant increase after CPB. On the other hand, the systolic blood pressure showed no significant change in group O after CPB. Three drugs showed no significant difference in the dosages of catecholamines used.     

The bridge treatment selected at the decision for transplantation did not affect the outcomes in patients with MDS

The optimal treatment for use as a bridge to allogeneic hematopoietic stem cell transplantation at the decision for transplantation has not been established in patients with myelodysplastic syndrome (MDS). We retrospectively evaluated the clinical outcomes after the decision for transplantation in our patients with MDS or acute myeloid leukemia (AML) secondary to MDS, aged more than 15 years, who underwent transplantation between 2007 and 2012. A total of 124 patients were included. We classified patients into two groups according to the bridge treatment selected at the decision for transplantation: Group 1, supportive care (n = 79), immunosuppressive therapy (n = 7), low‐dose chemotherapy (n = 12); Group 2, AML‐type induction chemotherapy (ICT: n = 22), azacitidine (Aza: n = 4). The rate of blasts in the bone marrow significantly influenced the treatment selection at the time of decision. There was no significant difference between the two groups in the rate of overall survival (OS) from the decision (73.1% vs 80.4% at 1 year) or from transplantation (59.0% vs 59.2% at 1 year). A significant difference was not observed even after patients were stratified according to either the rate of blasts in the bone marrow at the time of decision or the propensity score. In conclusion, the bridge treatment selected at the decision for transplantation did not affect the outcomes of transplantation in patients with MDS. However, this analysis did not include patients who could not undergo transplantation after the decision, and thus a prospective study is warranted. Copyright © 2015 John Wiley & Sons, Ltd.     

Neurodevelopmental delay up to the age of 4 years in infants born to women with gestational diabetes mellitus: The Japan Environment and Children's Study

Aims/IntroductionThis study aimed to investigate the neurodevelopment of infants born to women with gestational diabetes mellitus (GDM).Materials and MethodsData from the National Birth Cohort in the Japan Environment and Children''s Study from 2011 to 2014 (n = 81,705) were used. Japan uses the GDM guidelines of the International Association of Diabetes and Pregnancy Study Groups. The Japanese translation of the Ages and Stages Questionnaires, third Edition, was used to assess neurodevelopment in the following domains: communication skills, gross motor skills, fine motor skills, problem‐solving ability, and personal and social skills. The survey was carried out every 6 months from the age of 6 months to 4 years (total of eight times). Generalized estimating equations were used to evaluate the association between maternal GDM and neurodevelopmental delay based on odds ratios (ORs) and 95% confidence intervals (95% CIs).ResultsNeurodevelopmental delays, particularly in problem‐solving ability, fine motor skills, and personal and social skills, were significantly higher in infants born to women with GDM than in those born to women without GDM (adjusted OR 1.24, 95% CI 1.12–1.36; adjusted OR 1.15, 95% CI 1.03–1.27; and adjusted OR 1.18, 95% CI 1.04–1.33). Furthermore, stratification showed no significant increase in the adjusted ORs (95% CIs) of girls.ConclusionsNeurodevelopment was significantly delayed up to 4 years‐of‐age among boys born to women with GDM.     

Secondary Skin Cancer in a Case with Long-term Voriconazole after Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia

Secondary malignancies that develop after allogeneic-hematopoietic stem cell transplantation (allo-HSCT) have become serious issues. A 47-year-old man who developed acute myeloid leukemia in 2009 and subsequently underwent allo-HSCT twice: in 2009 and 2011. In 2015, voriconazole for lung aspergillus was started. In 2018, chronic graft-versus-host disease (GVHD) and multiple actinic keratoses manifested at his head. In 2020, some lesions were diagnosed as squamous cell carcinoma, so voriconazole was withdrawn, and subsequent surgery and radiation led to remission. Long-term administration of voriconazole in addition to allo-HSCT and chronic GVHD may be closely related to secondary skin cancer.