An adult patient with Kabuki syndrome presenting with Henoch-Schönlein purpura complicated with pulmonary hemorrhage

We present a case of a 33-year-old woman with Kabuki syndrome (KS) presenting with Henoch-Schönlein purpura (HSP). She was admitted to our hospital with a brain abscess in the lateral ventricle and meningitis. She had been diagnosed with KS. Skin eruptions had appeared on her lower extremities, with arthralgia, cough, and hemoptysis. She suddenly developed pulmonary hemorrhage and respiratory failure. We intubated her trachea and started mechanical ventilation in the intensive care unit (ICU). Skin biopsy revealed leukocytoclastic vasculitis with granular depositions of immunoglobulin A (IgA) in dermal vessel walls, and she was diagnosed as having HSP. Supportive management and prednisolone at 20 mg·day^?1 cured the pulmonary hemorrhage and respiratory failure. On ICU day 27, she was weaned from mechanical ventilation. Pulmonary hemorrhage as a complication of HSP is rare and sometimes fatal. KS is often associated with an increased incidence of infection and congenital heart disease. Susceptibility to infection and pulmonary hypertension due to congenital heart disease in this patient may have led to the development of the pulmonary hemorrhage. Supportive care and steroid therapy appeared to be beneficial in the treatment of this patient with HSP with pulmonary hemorrhage.     

Perimembrane Aurora-A Expression is a Significant Prognostic Factor in Correlation with Proliferative Activity in Non-Small-Cell Lung Cancer (NSCLC)

Purpose Aurora-A, also known as STK15/BTAK, is a member of the protein serine/threonine kinase family, and experimental studies have revealed that Aurora-A plays critical roles in cell mitosis and in carcinogenesis. However, no clinical studies on Aurora-A expression in non-small-cell lung cancer (NSCLC) have been reported. Thus, the present study was conducted to assess the clinical significance of Aurora-A status. Experimental Design A total of 189 consecutive patients with resected pathologic (p-)stage I-IIIA, NSCLC were retrospectively reviewed, and immunohistochemical staining was used to detect Aurora-A expression. Results Aurora-A expression was negative in 31 patients (16.4%); among Aurora-A positive patients, 124 patients showed pure diffuse cytoplasmic Aurora-A expression and the other 34 patients showed perimembrane Aurora-A expression. Perimembrane Aurora-A tumors showed the highest proliferative index (PI) (mean PIs for negative, diffuse cytoplasmic, and perimembrane tumors: 49.2, 41.7, and 63.5, respectively; P < .001). Five-year survival rates of Aurora-A negative, diffuse cytoplasmic, and perimembrane patients were 67.8%, 66.7%, and 47.6%, respectively, showing the poorest postoperative survival in perimembrane patients (P = .033). Subset analyses revealed that perimembrane Aurora-A expression was a significant factor to predict a poor prognosis in squamous cell carcinoma patients, not in adenocarcinoma patients. A multivariate analysis confirmed that perimembrane Aurora-A expression was an independent and significant factor to predict a poor prognosis. Conclusions Perimembrane Aurora-A status was a significant factor to predict a poor prognosis in correlation with enhanced proliferative activity in NSCLC.     

Three cases of acute pulmonary thromboembolism diagnosed by transesophageal echocardiography

We report 3 cases of acute pulmonary thromboembolism (PTE) diagnosed by transesophageal echocardiography (TEE). In all these cases, cardiovascular state of the patient was unstable and therefore computerized tomography and catheterization of the pulmonary artery for diagnosis of PTE could not be performed. TEE was useful for diagnosis of acute PTE. All three patients passed away eventually and we had a difficult experience for treatment of acute PTE. We should take various measures against deep vein thrombosis for prevention of acute PTE.     

Possible involvement of IkappaB kinase 2 and MKK7 in osteoclastogenesis induced by receptor activator of nuclear factor kappaB ligand.

Recent studies have revealed the essential role of the receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL) in osteoclast differentiation and activation. Adenovirus vector could efficiently transduce genes into RAW264.7 cells, which differentiate into osteoclast-like multinucleated cells in the presence of RANKL. The role of NF-kappaB and c-jun N-terminal kinase (JNK) activation in RANKL-induced osteoclast differentiation was investigated using an adenovirus vector carrying the dominant negative 1kappaB kinase 2 gene (AxIKK2DN) or dominant negative MKK7 gene (AxMKK7DN). IKK2DN and MKK7DN overexpression in RAW cells specifically suppressed the NF-kappaB activation and JNK activation in response to RANKL, respectively, without affecting other signaling pathways. Either inhibition of NF-kappaB or JNK pathways dose-dependently inhibited osteoclast formation induced by RANKL. These results suggest that both NF-kappaB and JNK activation are independently required for osteoclast differentiation.     

Insulin is a potent survival factor in mesangial cells: role of the PI3-kinase/Akt pathway

BACKGROUND: Elucidating the mechanisms of apoptosis is important for understanding the molecular mechanisms underlying glomerular disease. The phosphatidylinositol 3 kinase (PI3-kinase)/Akt pathway is essential for survival signaling in non-renal cells. However, little is known about the anti-apoptotic effect of insulin and the role of the PI3-kinase/Akt pathway in mesangial cells (MC) apoptosis. METHODS: Apoptosis was induced in wild type, p27Kip1 (p27) -/- and p21Cip1/Waf1 (p21) -/- mouse MC by survival factor withdrawal, actinomycin D, ultraviolet (UV)-B irradiation and cycloheximide in the presence or absence of insulin (1 micromol/L) or insulin-like growth factor-I (IGF-I; 100 ng/mL). The activation and levels of Akt, extracellular signal regulated kinase (ERK) and specific cell cycle proteins were determined by Western blot analysis. RESULTS: Insulin and IGF-I inhibited wild-type MC apoptosis induced by survival factor withdrawal, actinomycin D, ultraviolet-B irradiation and cycloheximide and in p27 -/- MC when apoptosis was induced by survival factor withdrawal. Akt was activated by insulin and IGF-I during apoptosis. Blocking PI3-kinase with LY294002 reduced Akt activation and abrogated the anti-apoptotic effect of insulin. ERK was activated during apoptosis and blocking ERK activation with U0126 or PD98059 partially rescued MC from apoptosis. Moreover, insulin also suppressed ERK activation during apoptosis. Our results also showed that the CDK-inhibitor p21 was increased by insulin and that p21 up-regulation was PI3-kinase/Akt pathway dependent. Furthermore, p21 -/- MC apoptosis induced by survival factor withdrawal was not rescued by insulin in contrast to the wild-type and p27 -/- MC. These data suggest that p21 may have a critical role in the anti-apoptotic effect of insulin. CONCLUSIONS: Insulin is a potent survival factor for MC in response to a number of different apoptotic triggers, and this effect is mediated through the PI3-kinase/Akt pathway. Moreover, ERK and p21 may be involved in anti-apoptotic effect of insulin in MC.     

Comparison of heart rate changes after neostigmine-atropine administration during recovery from propofol-N2O and isoflurane-2O anesthesia

Purpose. Propofol augments the reduction of heart rate (HR) in combination with cholinergic agents and attenuates the HR response to atropine. We examined whether propofol anesthesia was associated with an increased incidence and extent of bradycardia after neostigmine-atropine administration compared with the effects of isoflurane anesthesia. Methods. Thirty-six adult patients were randomly assigned to two groups (n = 18 each): the propofol group patients were anesthetized with propofol (5–10 mg·kg⁻¹·h⁻¹)-₂O-fentanyl, and the isoflurane group patients were anesthetized with isoflurane (0.5%–1.0%)-₂O-fentanyl. When surgery was completed, anesthetics were discontinued, and then a mixture of neostigmine 0.05 mg·kg⁻¹ and atropine 0.02 mg·kg⁻¹ was injected intravenously over 20 s. Blood pressure (BP) and HR were measured noninvasively at 1-min intervals for 10 min. Results. At the completion of the surgery, the average infusion rate of propofol was 6.2 ± 1.7 mg·kg⁻¹·h⁻¹, and the average inspired concentration of isoflurane was 0.73 ± 0.15%. Immediately before the neostigmine-atropine injections, HR and mean BP were similar in the two groups. The maximum increase in HR after the neostigmine-atropine injections was significantly less in the propofol group than in the isoflurane group (16 ± 9 and 34 ± 6 beats·min⁻¹, respectively, P < 0.01). The subsequent maximum decrease in HR was greater in the propofol group than in the isoflurane group (−9 ± 4 and −5 ± 4 beats·min⁻¹, respectively; P < 0.01). The incidence of bradycardia (HR < 50 beats·min⁻¹) after neostigmine-atropine injection was greater in the propofol group than in the isoflurane group (61% and 28%, respectively; P < 0.01). Conclusion. We conclude that propofol anesthesia attenuates the initial increases in HR, enhances the subsequent decreases in HR, and increases the incidence of bradycardia after neostigmine-atropine injections compared with the effects of isoflurane anesthesia. Received: May 21, 2001 / Accepted: August 29, 2001     

Recovery of postural stability following conscious sedation with midazolam in the elderly

Purpose. To investigate the differences in recovery of postural stability, after obtaining similar intravenous sedation levels with midazolam, in elderly and younger patients undergoing dental surgery. Methods. We studied 15 elderly patients (>65 years) and 15 younger patients (<55 years) after intravenous sedation. Midazolam was carefully titrated over 4–5 min until slow response to verbal commands, ptosis of the eyelid, or slight slurring of speech was obtained. Parameters were postural balance tests and an addition test, as a psychomotor function test. Results. The dose of midazolam in the elderly group (0.045 ± 0.012 mg·kg⁻¹) was 62% of that in the younger group (0.074 ± 0.026 mg·kg⁻¹). In evaluation of the percentile rank of a balance test with a visual feedback system, which contained a dynamic balance element, recovery at 60 min in the elderly group was significantly slower than that in the younger group. However, the recovery times for the balance test and the addition test, at which the significantly changed values were restored to the baseline values, were 120 min and 90 min, respectively, in both groups. Conclusion. In the recovery from sedation, elderly patients had more difficulty in acquiring postural adjustment during movement than in maintaining a standing posture. If the dose is carefully administered, however, even elderly patients might be able to return home 2 h after midazolam administration, as could the younger patients. Received: November 6, 2001 / Accepted: April 22, 2002     

The 4-portal technique decreases adverse effects in preoperative radiotherapy for advanced rectal cancer: comparison between the 2-portal and the 4-portal techniques

BACKGROUND: This study evaluated the difference of postoperative complications according to the radiation technique after preoperative radiotherapy for rectal cancer. METHODS: Among 224 patients with rectal cancer who underwent preoperative radiotherapy, 159 patients were treated with the 2-portal technique and 65 patients with the 4-portal technique. Comparison was performed between these 2 groups. RESULTS: The 5-year disease-free survival and local recurrence rate showed no difference between the 2 groups. There was also no difference in postoperative mortality. However, the 4-portal group had a significantly lower morbidity rate of 36.9% than the 2-portal group of 54.1% (P = .02). The rate of major complications that needed reoperation was also significantly lower in the 4-portal group (0%) than the 2-portal group (11.9%) (P = .01). The anastomotic leakage rate was significantly lower in the former (2.8% vs 20.0%, P = .033). CONCLUSION: The 4-portal technique is a better technique than the 2-portal technique for decreasing postoperative complications in preoperative radiotherapy for rectal cancer.     

Prognostic Significance of VEGF Expression in Correlation With COX-2, Microvessel Density,and Clinicopathological Characteristics in Human Gastric Carcinoma

Background Many studies have shown that angiogenesis plays an important role in the process of cancer development and progression. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity, and cyclooxygenase-2 (COX-2) supports angiogenesis by regulated production of angiogenic factors, including VEGF. The purpose of this study was to examine the expression of VEGF in combination with COX-2 and CD34, their correlation with various clinicopathological factors, and their prognostic significance in human gastric carcinoma. Methods Specimens from 169 patients with different grade and stage gastric carcinoma were investigated by immunohistochemistry for COX-2 and VEGF expression. Tumor microvessel density was assessed with CD34 immunostaining. Correlations between the expression of VEGF, COX-2, CD34, and various clinicopathological factors were studied. The effect of these proteins on patient survival was determined. Results COX-2 and VEGF were positively expressed in 36.7% and 50.3% of the patients, respectively. Positive correlation was found between VEGF and COX-2 and between VEGF and CD34. VEGF expression was correlated with depth of invasion; metastatic lymph nodes; lymphatic and venous invasion; and tumor, node, metastasis system stage. Patients with positive staining for VEGF showed far lower disease-free (64.9% vs. 81.3%) and overall (58.3% vs. 76.9%) survival rates than VEGF-negative patients. In multivariate analysis, only tumor location, depth of invasion, and lymph node metastasis were shown to be independent prognostic factors. Conclusions VEGF expression correlates with angiogenesis and tumor progression and is a valuable prognostic factor in patients with gastric carcinoma.     

Immunosuppressive activity of serum taken from a liver transplant recipient after withdrawal of immunosuppressants

In orthotopic liver transplantation (OLT), tolerance is induced in a certain combination of donors and a recipient in rats and, in some clinical cases, rejection has not occurred in OLT patients after weaning off immunosuppression. However, this mechanism has not yet been elucidated. Among our cases of liver transplantation (LTx), one OLT patient (Patient A) has not required immunosuppressive drugs for the last 5 years, following post-transplant lymphoproliferative disease (PTLD). This patient's serum interleukin-2 levels were undetectable following withdrawal of immunosuppressants. The same serum taken after discontinuing the immunosuppressants inhibited concanavalin A blast cultured cells and up-regulated the IL-4/IFN-gamma gene expression ratio. These results suggested that other proteins were induced following withdrawal of immunosuppressants. Proteomic assay demonstrated 12 differentiated spots exclusive to this patient where immunosuppressants have been discontinued. Haptoglobin, found to have immunosuppressive activity in vitro, may play an important role in the maintenance of drug-free tolerance as a natural immunological suppressor after cessation of immunosuppression. Proteomic analysis will allow us to develop a novel weaning protocol for patients on long-term immunosuppression to avoid major immunosuppressant-related complications.