Severe aortic insufficiency due to a huge leaflet perforation in Libman-Sacks syndrome: Report of a case

A 40-year-old woman who was diagnosed to have systemic lupus erythematosus developed complications of cerebral infarction and alveolar hemorrhage. Close examination revealed severe aortic insufficiency, and she was diagnosed with Libman-Sacks syndrome. Due to progressive dilatation of the left ventricle and her easily fatigued state, surgery was performed. On pathological examination, holes of 4-mm and 5-mm diameter were detected in the left coronary and noncoronary cusps of the aortic valve, respectively. The morphology of the valve lesions showed a characteristic shape of such huge holes.     

Novel multidrug therapy for children with cyclosporine-resistant or -intolerant nephrotic syndrome

An effective treatment for children with refractory nephrotic syndrome (NS), especially in those with cyclosporine (CsA)-resistant or CsA-intolerant NS, has yet to be established. Recently, the efficacy of multidrug therapy consisting of tacrolimus (Tac), mycophenolate mofetil (MMF) in combination with prednisolone (PDN) in adult patients with refractory NS has been reported. We successfully treated 14 consecutive children with refractory CsA-resistant or CsA-intolerant NS using combination therapy consisting of relatively low-dose Tac, mizoribine (MZR), which has a mechanism of action very similar to that of MMF, and PDN. There were no serious clinical toxicities. Of the 14 children, 9 with a mean age of 13.0 years had steroid-dependent NS (SDNS) and 5 with a mean age of 9.6 years had steroid-resistant NS (SRNS). All SDNS patients had minimal change disease (MCD), 4 with SRNS had focal segmental glomerulosclerosis (FSGS), and the remaining child had MCD on renal biopsy. All patients were in a prospective cohort, but were evaluated retrospectively. The mean follow-up from the initiation of multidrug therapy was 18.4 months in SDNS and 18.6 months in SRNS patients. At the last observation point, the calculated relapse rate and minimum dose of PDN required for maintenance of clinical remission after the start of multidrug therapy were significantly decreased compared with those prior to this therapy, while on CsA, in SDNS patients (0.4?±?0.5 times/year vs 2.9?±?1.5 times/year, P?=?0.0077, and 0.3?±?0.2 mg/kg on alternate days vs 0.5?±?0.2 mg/kg on alternate days, P?=?0.0184 respectively). All SDNS and two SRNS patients (40%) achieved complete remission, allowing further decreases in the minimal doses of PDN required for maintenance of clinical remission in most our patients. However, one patient with FSGS remained refractory to multidrug therapy and subsequently developed end-stage renal disease. These clinical observations, although preliminary and involving a small number of patients, suggest that multidrug therapy consisting of relatively low-dose Tac, MZR, and PDN might be effective and safe for treating children with refractory CsA-resistant or CsA-intolerant NS. However, further studies involving larger numbers of patients are needed.     

Reductions in bone turnover, mineral, and structure associated with mechanical properties of lumbar vertebra and femur in glucocorticoid-treated growing minipigs

The present study was designed to determine the effects of glucocorticoid (GC) on bone turnover, minerals, structure, and bone mechanical properties in minipigs. Six 8-month-old G?ttingen minipigs were subcutaneously injected with prednisolone (PN, 0.5 mg/kg body wt (BW)/day, 5 days/week for 26 weeks (Group GC)), 6 were treated with vehicle alone (Group VC), and 4 were sacrificed at start of the study for baseline controls (Group BC). The increase in BW was similar in all groups. PN significantly reduced serum osteocalcin and urinary type-1 collagen N-telopeptide levels at 13 weeks and thereafter, compared with baseline and control, and also reduced serum bone specific alkaline phosphatase levels relative to baseline. At 26 weeks, the longitudinal axis of the lumbar bone and length of femur were smaller in Group GC than Group VC. The total cross-sectional area of femur, but not the lumbar bone, in Group GC was significantly different from Group VC. BMD of the femur, but not L2, measured by DXA, was lower in Group GC than in Groups BC and VC. The cortical shell structure measured by 2D-micro-CT deteriorated and age-dependent increases in trabecular bone structure 3D micro-CT were reduced by PN. PN also caused deterioration of the cortical structure of the mid-femur. In L2 and femur, PN significantly reduced the ultimate load and maximum absorption energy of the femur and L2 compared with Group VC. The structural modulus in Group GC was lower than in Group BC. Regression analyses revealed that bone minerals, bone structure, and chemical markers correlated with mechanical properties of L2 and mid-femur. Our results indicate that PN reduced systemic bone formation and resorption and suppressed the age-dependent increases in bone minerals, structure, and mechanical properties of L2 and mid-femur. Reduced bone turnover seemed to be associated with a reduction in mechanical properties. The growing minipig could be a suitable model of GCs-induced osteoporosis in humans.     

Alpha-fetoprotein-producing early gastric cancer: report of two cases

We have experienced two cases of alpha-fetoprotein (AFP)-producing early gastric cancer. One patient was a 73-year-old man diagnosed as having an early gastric cancer type 0 I + IIa at 40 x 40 mm on the greater curvature of the lower body of the stomach. The histological findings showed that proliferation of a well-differentiated tubular adenocarcinoma with hepatoid pattern was massively invading to the middle layer of the submucosa, with positive lymph vessel, and lymph node metastasis. The other patient was a 76-year-old man diagnosed as having an early gastric cancer type 0 IIa + IIc at 25 x 25 mm on the anterior wall on the greater curvature of the antrum. The histological findings showed that proliferation of a small cell carcinoma was massively invading to the deep layer of the submucosa, with positive lymph vessel, and lymph node metastasis. AFP was immunohistochemically found in the tumor cells of these two cases. Both patients died from liver metastasis. AFP-producing early gastric cancer was concluded to be at high risk of liver metastasis.     

Methylcobalamin amplifies melatonin-induced circadian phase shifts by facilitation of melatonin synthesis in the rat pineal gland

Effects of methylcobalamin (methyl-B₁₂), a putative drug for treating human circadian rhythm disorders, on the melatonin-induced circadian phase shifts were examined in the rat. An intraperitoneal injection of 1–100 μg/kg melatonin 2-h before the activity onset time (CT 10) induced phase advances of free-running activity rhythms in a dose-dependent manner (ED₅₀=1.3 μg/kg). Injection of methyl-B₁₂ (500 μg/kg) prior to melatonin (1 μg/kg) injection induced larger phase advances than saline preinjected controls, while the injection of methyl-B₁₂ in combination with saline did not induce a phase advance. These results indicate amplification of melatonin-induced phase advances by methyl-B₁₂. Pinealectomy abolished the phase alternating effect of methyl-B₁₂, suggesting a site of action within the pineal gland. In fact, methyl-B₁₂ significantly increased the content of melatonin in the pineal collected 2-h after activity onset (CT 14). In contrast, no difference in melatonin content was found at CT 10, indicating that the effect of methyl-B₁₂ may be gated after the activity onset time when endogenous melatonin synthesis is known to increase. These results suggest that methyl-B₁₂ amplifies melatonin-induced phase advances via an increase in melatonin synthesis during the early subjective night at a point downstream from the clock regulation.     

HEMATOGENOUS DEVELOPMENT OF RAT MATURE GRANULOCYTIC LEUKEMIA

The oral administration of N, N'-2, 7-fluorenylenebisacetamide (2, 7-FAA) induces leukemia, especially mature granulocytic leukemia, in rats. We compared the distribution of nodular foci of 2,7-FAA-induced mature granulocytic leukemia with that of transplanted leukemia for the purpose of proving hematogenous development of leukemia. The bone marrow of the vertebral bodies was examined in the cases of scattered lesion of 2,7-FAA-induced and transplanted leukemia. The leukemic nodular foci were most frequently located around the center of the craniocaudal axis of the vertebral bodies in both leukemias. On the other hand, they were evenly distributed along the dorso-ventral axis in both leukemias. The similarity of the distribution of nodular foci between 2,7-FAA-induced and transplanted leukemia may be an evidence for the hypothesis that the former is spread by hematogenous metastasis.     

Monitoring human exposures to upper-room germicidal ultraviolet irradiation

After decades of neglect, the resurgence of tuberculosis in the United States between 1985 and 1992 renewed interest in the use of upper room ultraviolet germicidal irradiation to interrupt the transmission of airborne infections. More recently the bioterrorism threat and the appearance of new pathogens with the potential for airborne spread, such as severe acute respiratory syndrome (SARS), have stimulated installations of upper-room irradiation systems. The objective is to flood the entire volume of a room above 6.5 ft with high intensity ultraviolet germicidal irradiation, while minimizing unintentional irradiance below 6.5 ft to avoid eye and skin irritation. Air exchanges between the upper and lower room result in air disinfection of the occupied space. Designers of these systems have adopted the practice of limiting the maximum lower room irradiance at every point to less than the continuous 8-hour time-weighted average threshold limit value, severely limiting the irradiation intensity in the upper room and thereby reducing one of the two major factors determining germicidal effectiveness, the other being room air mixing. The hypothesis of this study is that eye and skin exposure will be well below the recommended safe dose even when maximum eye-level irradiance levels in the room exceed the 8-hour continuous exposure threshold limit. The method employed was to have subjects wear a small photometer that recorded total ultraviolet dose over the period of exposure while subjects went about their normal routine, and comparing this value with a hypothetical dose calculated from the highest measured eye-level irradiance. The results of the study, based on a limited number of observations, confirmed the hypothesis. Observed doses were one-third to a factor of a hundred or more lower than the doses calculated from maximum eye-level irradiances measurements in the occupants' spaces.     

Effects of sporadic transthyretin amyloidosis frequently on the gallbladder and the correlation between amyloid deposition in the gallbladder and heart: A forensic autopsy-based histopathological evaluation

The aim of the study is to evaluate the clinicopathological features of cholecystic ATTR deposition in patients with cardiac involvement, investigate the correlation of amyloid deposition severity in the gallbladder and the heart, and compare its prevalence in the gallbladder and other organs. Fifty patients with sporadic ATTR amyloidosis were identified. Of these, we evaluated 15 patients who underwent gallbladder sampling accurately. Among 10 patients (67%) with cholecystic deposition, six exhibited detectable deposition in the hematoxylin and eosin-stained specimens, and all of them displayed obstructive vascular deposition (VD). The severity of gall bladder VD was statistically correlated with that of cardiac VD and atrial interstitial deposition (ID). Additionally, all patients exhibiting cholecystic ID displayed severe ventricular and atrial IDs. In visceral organs excluding the heart, amyloid deposition was commonly observed in the lungs (93%), followed by the gastrointestinal tract (47%‒80%), liver (60%) and periosteal tissues (53%). The involvement of the gallbladder was prevalent and comparable to that of the gastrointestinal tract. Moreover, the severity of cholecystic deposition was correlated with that of cardiac deposition. Therefore, pathologists should be aware that sporadic ATTR amyloidosis is a common condition and should not be overlooked.