The relationship between serum levels of estradiol and osteoprotegerin in patients with anorexia nervosa

Osteoporosis is one of the major complications in anorexia nervosa (AN) patients. Receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) have been identified as important regulators of bone turnover. The objective of this study was to clarify the role of RANK-RANKL-OPG system, and their relationship with other regulators for bone metabolism in AN patients. We investigated serum levels of RANKL, OPG, and bone turnover markers of 26 Japanese young female AN patients and 7 age-matched healthy women. We measured serum levels of estradiol (E2), insulin like growth factor-I (IGF-I) and triiodothyronin (T3) from the same samples and studied their relationship with RANKL or OPG. Mean serum levels of E2, IGF-I, T3 and leptin in AN patients were significantly lower than those of controls (p<0.05). Serum levels of OPG in AN patients were significantly higher than those in controls and negatively correlated with body mass index (BMI), E2, IGF-I or leptin. Serum levels of free RANKL could not be detected except for only one healthy control in both groups. These results suggest that serum OPG levels may be increased by a compensatory mechanism for malnutrition and estrogen deficiency which induces an increase in bone resorption.     

Phase I trial of gemtuzumab ozogamicin in intensive combination chemotherapy for relapsed or refractory adult acute myeloid leukemia (AML): Japan Adult Leukemia Study Group (JALSG)-AML206 study

In order to investigate better molecular-target therapy for acute myeloid leukemia (AML), we conducted a phase I trial of a combination of gemtuzumab ozogamicin (GO) with conventional chemotherapy. Between January 2007 and December 2009, a total of 19 adult Japanese patients with relapsed or refractory CD33-positive AML (excluding acute promyelocytic leukemia) were enrolled. All registered patients received a standard dose of cytarabine (Ara-C) (100 mg/m(2) × 7 days), combined with either idarubicin (IDR) (10-12 mg/m(2) × 3 days) or daunorubicin (DNR) (50 mg/m(2) × 3-5 days), and then GO (3-5 mg/m(2) ), which was administered 1 day after the last infusion of IDR (IAG regimen) or DNR (DAG regimen). While doses of both GO and IDR and the administration period of only DNR were increased, the dose-limiting toxicity (DLT) was assessed. Among 19 patients (nine in the IAG regimen, 10 in the DAG regimen), the median age was 59 years (range 33-64), and the relapsed/refractory ratio was 13/6. In the therapy using 3 mg/m(2) GO in the IAG or DAG regimen, grade 3/4 leukopenia and neutropenia were observed in all patients, but none had grade 3/4 non-hematological toxicities, except febrile neutropenia. Three patients in the IAG regimen who were administered 5 mg/m(2) GO showed DLT. No patients had veno-occlusive disease or sinusoidal obstructive syndrome. In conclusion, 3 mg/m(2) GO combined with Ara-C and IDR or DNR can be safely administered, and phase II trials should be conducted to investigate the clinical efficacy of the combination therapy.     

Surgical outcome of stage III and IV adrenocortical carcinoma

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare tumor usually diagnosed at an advanced stage on invasion of or adherence to adjacent organs. We report surgical outcome of stage III and IV ACCs. METHODS: ACCs from seven patients at clinical stage II (n = 1), III (n = 4), or IV (n = 2) were resected. Combined resection of the liver and inferior vena cava was performed in six patients. Morbidity, mortality, recurrence and survival were analyzed. RESULTS: The pathological stage was stage III in five patients and stage IV in two patients. The mortality was zero and the morbidity was two of seven (29%) patients. The estimated 3-year disease-free and overall survivals for stage III were 20% and 40%, respectively, with a median follow-up of 32 months (range, 11-58). The mean disease-free survival was 21.0 +/- 9.0 months (95% CI: 3.3-38.7). The 3-year disease-free and overall survivals for stage III and IV were 14.3% and 28.6%, respectively. The mean disease-free survival time was 18.6 +/- 6.7 months (95% CI: 5.4-31.8). The most frequent site of metastasis was the lungs, seen in four patients, and liver in three patients. Loco-regional, intra-abdominal lymph node, peritoneum, bone, brain recurrences were also seen in one patient each. The mean survival after recurrence was 19.0 +/- 3.3 months (95% CI: 12.6-25.5), and the 50% survival was 18.4 months with mitotan and cytotoxic drug therapy. CONCLUSIONS: Resection for stage III, IV ACCs affords the possibility of negative margins, acceptable peri-operative morbidity and mortality, and prolongs survival in selected patients.     

Correlation between salivary alpha-amylase activity and pain scale in patients with chronic pain

BACKGROUND AND OBJECTIVES: The visual analog scale (VAS) is commonly used to assess pain intensity. However, the VAS is of limited value if patients fail to reliably report. Objective assessments are therefore clearly preferable. Previous reports suggest that elevated salivary alpha-amylase may reflect increased physical stress. There is a close association between salivary alpha-amylase and plasma norepinephrine under stressful physical conditions. In this study, we have determined the usefulness of a portable salivary alpha-amylase analyzer as an objective biomarker of stress. METHODS: Thirty patients (male/female = 15/15, age: 60.5 +/- 15.3 years) with chronic low back or leg pain (pain (+) group) and 20 pain-free control patients undergoing elective surgery under general anesthesia with epidural analgesia (pain (-) group) were recruited. Patients received epidural block with 5 to 10 mL 1% lidocaine. VAS, blood pressure, and heart rates were assessed before and 30 and 45 minutes after the epidural block. Salivary alpha-amylase was simultaneously measured using a portable analyzer. The relationship between the VAS and salivary alpha-amylase in chronic pain patients was assessed. RESULTS: After the epidural block both heart rate and systolic blood pressure decreased by approximately 8%. In the pain (+) group, the epidural block markedly decreased the VAS pain scale and salivary alpha-amylase from 56 +/- 22 to 19 +/- 16 mm (P < .01) and from 82 +/- 48 to 45 +/- 28 U/mL (P < .01), respectively, with a significant correlation between the 2 measures (r = 0.561, P < .01). In contrast, salivary alpha-amylase did not change significantly in the pain (-) group. CONCLUSIONS: Because there was a significant correlation between VAS pain scale and salivary alpha-amylase, we suggest that this biomarker may be a good index for the objective assessment of pain intensity. In addition, a simple to use portable analyzer may be useful for such assessment.     

Urinary excretions of albumin and type IV collagen in normotensive and hypertensive subjects.

Plasma albumin leaks into urine as a result of glomerular hypertension and basement membrane injury, while urinary type IV collagen derives from mesangial matrix and glomerular basement membrane. The purpose of this study was to elucidate the pathophysiological significance of these urinary microproteins as an indicator of cardiovascular organ injuries in hypertension. In health-checkup participants without diabetes, proteinuria, or microhematuria, and who were not being treated for hypertension or any other disease at the time of enrollment, urinary albumin and type IV collagen were measured and their relations to organ injuries and cardiovascular risk factors were evaluated. Of 1,079 subjects (40- to 65-year-old; 256 men and 823 women) enrolled in the study, 120 (11.1%) had untreated hypertension exceeding 140/90 mmHg. Urinary albumin was positively correlated with both age (r=0.16, p<0.001) and systolic blood pressure (r=0.27, p<0.001). Urinary type IV collagen was not only positively correlated with age (r=0.12, p<0.001) and diastolic blood pressure (r=0.14, p<0.001) but also negatively correlated with blood hemoglobin (r=-0.12, p<0.001). Urinary albumin, but not type IV collagen, had a significant relation to electrocardiographic signs of left ventricular hypertrophy (p=0.012) and retinal arteriosclerosis on fundoscopy (p <0.001). Thus both albumin and type IV collagen would seem to have increased in association with age and hypertension in this cohort. It is suggested that urinary albumin is an indicator not only of renal injury, but also possibly of development of cardiac hypertrophy and arteriosclerotic changes. Urinary type IV collagen, on the other hand, may be associated with renal tissue injuries that affect erythrokinetics.     

Different contribution of apoptosis to the antiproliferative effects of L-arginine, enalapril and losartan on neointimal growth inhibition after balloon arterial injury.

It remains to be clarified how angiotensin-converting enzyme inhibitor-induced function (ie, increased NO related action or the inhibition of angiotensin II AT1 receptor dependent action) affects apoptosis of smooth muscle cells in the neointima following arterial injury. Saline (control), enalapril, L-arginine, combined enalapril and L-arginine, or losartan was administered for 14 days to Sprague-Dawley rats after balloon carotid injury and the ratio of intima to media areas (I/M), inducible NO synthase (iNOS) concentrations and %TUNEL were measured. I/M decreased similarly in the enalapril, L-arginine and losartan groups, and the combination of enalapril and L-arginine resulted in the largest I/M decrease. TUNEL positivity was increased compared with controls in the following order: losartan, L-arginine, enalapril and combination of enalapril and L-arginine. The intensity of immunostaining for iNOS was increased approximately 1.9-fold compared with the control in the combined enarapril and L-arginine group as well as in the enalapril group. These data suggest that the apoptosis in the neointima is different for L-arginine, losartan and enalapril under similar conditions and was higher under treatment with enalapril, not only via the action of NO or blocking of the AT1, but also by upregulation of iNOS.     

Immunohistochemical localization of secretory component and IgA in the normal and cancerous endometrium

Using normal and cancerous endometrial tissues obtained from climacteric and postmenopausal women as the subjects, localizations of secretory component (SC) and IgA were immunohistochemically investigated. The results were as follows: Similar to cyclic women, in normal endometrial tissues from climacteric and postmenopausal women, SC and IgA localized mainly in glandular epithelia. However, in women over 60 years of age, immunoreactivity of SC and IgA decreased. In cancerous tissues, staining intensity of SC and IgA decreased clearly as compared to normal tissues. Also, the loss of polarity was recognized in the localization pattern of SC and IgA. In relation to the tissue differentiation, a further decline was recognized in the SC and IgA staining intensity in the poorly differentiated carcinoma as compared to the well differentiated type. The above findings suggested that the decline of the local immune system in the endometrium, namely, weakening of the local defense mechanism against infections, took place in women of advanced age. Also it was recognized that weakening of the ability to produce SC was caused by the malignant transformation of endometrium, and it was suggested that SC was a substance which had a close relationship to tissue differentiation.     

Lymphangiomyomatosis with a large retroperitoneal tumor]

A case of lymphangiomyomatosis (LAM) in a 35-year-old woman is reported. Because she was already severely dyspneic when she was admitted to our hospital, neither TBLB nor open lung biopsy was performed, and no accurate diagnosis was made. She died of respiratory failure three years after the development of exertional dyspnea, and autopsy revealed LAM. Pneumothorax, a well-known and frequent complication of LAM, did not occur until one month prior to her death. Although pneumothorax frequently complicates LAM, there are a few reports of cases in which pneumothorax did not occur during the course of the disease. We emphasize that LAM should be considered in the differential diagnosis of diffuse interstitial lung disease, even when the patient has no pneumothorax. The retroperitoneal tumor (15 x 10 x 10 cm), which was evident clinically, was later shown to be intra-abdominal involvement of LAM. Although only a few cases of LAM with a large retroperitoneal tumor have been reported, minor intra-abdominal involvement is relatively common. This case also suggested that the finding of a retroperitoneal tumor may be a diagnostic clue in LAM.     

Fundus hemorrhage in patients with intracranial hemorrhage caused by cerebrovascular disease--its clinical significance]

To clarify the significance of fundus hemorrhage in the acute stage of intracranial hemorrhage due to cerebrovascular disease (HCVD), the incidence of such hemorrhage (retinal, preretinal, and subhyaloid hemorrhage) was examined and its correlations with the severity of the disturbance of consciousness and the prognosis were investigated. Two hundred sixteen HCVD patients with intracranial hemorrhage were the subjects of this study, including 87 cases of subarachnoid hemorrhage (SAH), 60 cases of hypertensive intracerebral hemorrhage (HICH), 54 cases of arteriovenous malformation (AVM), and 15 cases of Moyamoya disease. Fundus hemorrhage was recognized in 41 cases of SAH (47%), 5 cases of HICH (8%), 3 cases of AVM (6%), and 2 cases of Moyamoya disease (13%). The incidence of fundus hemorrhage was significantly higher in SAH than in the other type of HCVD associated with intracranial hemorrhage. Among patients with severe disturbance of consciousness (JCS 100-300), fundus hemorrhage was recognized in 69% with SAH, 13% with HICH, 17% with AVM, and none with Moyamoya disease. Therefore, patients with both fundus hemorrhage and severe disturbance of consciousness in the acute stage are most likely to have SAH, but HICH and AVM should be also taken into consideration. In patients with slight disturbance of consciousness (JCS 0-30), fundus hemorrhage was only noted in SAH (27%) and not in other types of HCVD associated with intracranial hemorrhage. Thus, SAH is highly likely to be the primary HCVD associated with intracranial hemorrhage, if we recognize fundus hemorrhage in patients with slight disturbance of consciousness in the acute stage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adjacent segment stenosis after lumbar fusion requiring second operation

Background Whereas degeneration of the segment adjacent to lumbar fusion has been often seen on radiographs, a small number of patients with such degenerative changes undergo reoperation. Most follow-up studies have focused on adjacent segment disease based on analysis of radiographs. The present study was conducted to understand the pathology of reoperation cases of adjacent segment disease and factors associated with this condition. Operative indication was consistently restricted to patients with neurological involvement. Methods The subjects were 117 patients who had undergone posterior lumbar fusion and were followed for a minimum of 2 years (mean 7 years). Among them, nine patients (7.7%) required a second operation owing to symptomatic adjacent segment disease (stenosis). The reoperation rate was assessed in relation to sex, age, initial pathologic condition, and initial spinal fusion and decompression methods. Data were analyzed in a 2 × 2 cross contingency table using Fisher's exact probability test. A probability of <0.05 was defined as statistically significant. Results Of the variables examined, only multilevel fusion was associated with a high rate of reoperation with statistical significance (P < 0.04). Two patients (100%) suffering from loss of coronal balance (degenerative scoliosis) also required a second operation. Conclusions The reoperation rate of 7.7% for adjacent segment disease in this study was consistent with the prevalence of adjacent segment stenosis in the literature. Given the risk of later occurrence of adjacent segment stenosis following multisegment posterolateral fusion, correction of coronal and sagittal balance, preventive decompression of the adjacent segment, or selective decompression without fusion may have to be considered as an additional or alternative procedure.