Feasibility of acute physiology and chronic health evaluation (APACHE) II and III score-based screening in patients receiving allogeneic hematopoietic stem-cell transplantation

Patients who require management in the intensive care unit (ICU) for complications after allogeneic hematopoietic stem-cell transplantation (HSCT) generally have a poor outcome. We retrospectively studied whether the risk-prediction stratification systems commonly used for patients admitted to the ICU, that is, the Acute Physiology and Chronic Health Evaluation (APACHE) II and APACHE III systems, could be useful for identifying patients who should receive intensive care earlier. We reviewed the medical records of 210 patients who underwent allogeneic HSCT and found that 18 (8.6%) had been admitted to the ICU for acute respiratory failure (n=9), acute renal failure (n=7), and septic shock (n=2). The median APACHE II and III scores were, respectively, 16 (10-27) and 55 (22-87) at the onset of complications and 26 (15-43) and 101 (65-157) upon admission to the ICU. Thus, both the APACHE II and APACHE III scores at ICU admission were higher than those at the onset of complications (P <0.0001). Seventeen patients (94%) subsequently died, with a median ICU stay of 7.5 days (1-51 days), as a result of multiorgan failure (n=14), respiratory failure (n=2), and septic shock (n=1). The APACHE II and III scores of the sole surviving patient were, respectively, 21 and 71 at the onset and 24 and 86 upon transfer to the ICU. Thus, the APACHE scores in this study were lower than those reported for other surgical or medical patients treated in the ICU, despite their uniform poor prognosis. Although nine patients had developed grade III to IV acute graft-versus-host disease, which is the most common cause of morbidity and mortality after allogeneic HSCT, this was not fully evaluated in the current scoring systems. Application of these systems to HSCT will require adequate modification, with particular attention to organ dysfunction secondary to graft-versus-host disease.     

NPHS2 mutations in sporadic steroid-resistant nephrotic syndrome in Japanese children

Podocin is an integral membrane protein encoded by NPHS2, which is mapped to 1q25-31 and is exclusively expressed in glomerular podocytes. NPHS2 mutations are responsible for autosomal recessive familial steroid-resistant nephrotic syndrome (SRNS) with minor glomerular abnormalities or focal segmental glomerulosclerosis (FSGS), which is characterized by early childhood onset (age less than 6 years) and rapid progression to chronic renal insufficiency. This gene mutation is also responsible for an adolescent/adult onset form of autosomal recessive familial FSGS with heavy proteinuria. It has been demonstrated that sporadic SRNS and heavy proteinuria are also due to NPHS2 gene mutations. We isolated genomic DNA from 36 Japanese children with chronic renal insufficiency caused by SRNS or heavy proteinuria, and analyzed all eight exons and exon-intron boundaries of NPHS2 using the polymerase chain reaction and direct sequencing. The age at onset of disease was 3.9+/-0.5 years. There were 29 patients with SRNS and 7 with heavy proteinuria without nephrotic syndrome at the onset, but all patients developed chronic renal insufficiency 4.6+/-0.8 years after the onset. A new homozygous missense variant of NPHS2, G34E (G101A) in exon 1, was detected in 1 of 36 patients. However, this homozygous variant was also found in 1 of 44 normal controls, suggesting that the mutation is a polymorphism. Two silent variants (T954C and A1038G) in exon 8 of this gene were also identified in some of the patients and normal controls, indicating that the silent variants are also polymorphisms. There was no significant difference in the genotypic and allelic frequencies of T954C and A1038G polymorphisms between the patients and normal controls. In conclusion, NPHS2 gene mutations are not a major cause of chronic renal insufficiency caused by sporadic SRNS or heavy proteinuria in Japanese children.     

Distinct response of experimental neuroblastoma to combination antiangiogenic strategies

Background: The authors have shown previously that experimental neuroblastoma is partially inhibited (48%) by antivascular endothelial growth factor (anti-VEGF) antibody. The topoisomerase-I inhibitor, topotecan, has been shown to have antiangiogenic activity when administered in a low-dose, high-frequency regimen. We hypothesized that combining topotecan with anti-VEGF would suppress neuroblastoma more effectively than either agent alone. Methods: A total of 10⁶ neuroblastoma cells were implanted intrarenally in athymic mice. Animals received vehicle, topotecan, anti-VEGF, or topotecan plus anti-VEGF (n = 9, 20, 20, 20, respectively). All control and half the treated mice were killed at 6 weeks. Remaining (rebound) mice were maintained without treatment for 3 more weeks. Patterns of vasculature and apoptosis were determined immunohistochemically. Results: Tumor weights at 6 weeks were reduced significantly in topotecan-only (0.07g) and combination-treated animals (0.08 g), compared with controls or anti-VEGF[ndash ]treated mice (1.18 g, 0.53 g; P [lt ] .0007, all). At 9 weeks, rebound tumor weights were greatest in anti-VEGF (2.82 g), intermediate in topotecan (1.82 g), and least in combination-treated animals (1.47 g); however, the only significant difference was between anti-VEGF and combination therapy (P = 0.04). All treated tumors were vascularized sparsely in comparison with controls at 6 weeks, but exhibited brisk neoangiogenesis at 9 weeks. Conclusions: Topotecan either with or without anti-VEGF antibody significantly suppresses neuroblastoma xenograft growth in comparison with controls or anti-VEGF antibody alone. Combining topotecan with anti-VEGF antibody significantly inhibited rebound tumor growth in comparison with anti-VEGF antibody alone. Combination therapy may improve durability of antiangiogenic inhibition of neuroblastoma.     

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.     

An autopsy case of Down's syndrome with moyamoya syndrome

We reported an autopsy case of Down's syndrome with moyamoya syndrome. A 30-year-old male with Down's syndrome suffered from a cerebral infarction and died of brain herniation. Cerebral angiography showed vascular abnormalities that were the same as moyamoya disease. Pathological findings revealed multiple stenosis of main trunk of the cerebral arteries. Pathologically, the stenosed vessels showed eccentric intimal thickness with cholesterin deposit, unlike moyamoya disease. There are only two previous reports of autopsied cases of Down's syndrome with moyamoya syndrome. We postulate that a protein encoded on chromosome 21 may be related to the pathogenesis of Down's syndrome with moyamoya syndrome.     

Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: Eight-year experience

Objective:   To report on the long-term results of high-intensity focused ultrasound in the treatment of localized prostate cancer.
Methods:   A total of 517 men with stage T1c–T3N0M0 prostate cancer treated with Sonablate devices (Focus Surgery, Indianapolis, IN, USA) between January 1999 and December 2007 were included in the study. Biochemical failure was defined according to the Phoenix definition (prostate-specific antigen nadir + 2 ng/mL).
Results:   The median follow-up period for all patients was 24.0 months (range, 2 to 88). The biochemical disease-free rate (BDFR) in all patients at 5 years was 72%. The BDFR in patients with stage T1c, T2a, T2b, T2c and T3 groups at 5 years were 74%, 79%, 72%, 24% and 33%, respectively ( P  < 0.0001). BDFR in patients in the low, intermediate and high-risk groups at 5 years were 84%, 64% and 45%, respectively ( P  < 0.0001). The BDFR in patients treated with or without neoadjuvant hormonal therapy at 7 years were 73% and 53% ( P  < 0.0001), respectively. In multivariate analysis, pretreatment prostate-specific antigen levels (hazard ratio 1.060; P  < 0.0001; 95% confidence interval 1.040–1.080), neoadjuvant hormonal therapy (hazard ratio 2.252; P  < 0.0001; 95% confidence interval 1.530–3.315) and stage ( P  = 0.0189) were demonstrated to be statistically significant variables. Postoperative erectile dysfunction was noted in 33 out of 114 (28.9%) patients who were preoperatively potent.
Conclusions:   High-intensity focused ultrasound therapy appears to be minimally invasive, efficacious and safe for patients with localized prostate cancer, particularly those with low- and intermediate-risk cancer.     

Changes in core temperature associated with lower extremity tourniquet--the influence of ambient temperature and warming equipments

BACKGROUND: We investigated changes in core temperature associated with lower extremity tourniquet (TQ) under two different ambient temperatures (1) and two different warming equipments (2) under general anesthesia combined with lumbar epidural anesthesia. METHODS: (1) The values of core temperature at ambient temperature of either 22 degrees C (n = 15) or 20 degrees C (n=15) were recorded after induction of anesthesia, at start of TQ application, at the termination of TQ application, and 14 minute after TQ release. (2) The values of core temperature using either air-forced warming or active heated i.v. at ambient temperature 20 degrees C were recorded at four points as mentioned above. RESULTS: (1) Changes in core temperature were not observed during TQ application at ambient temperature both 20 degrees C and 22 degrees C. Core temperatures in both groups decreased significantly after TQ release, and core temperatures at termination of TQ application and after TQ release at ambient temperature 20 degrees C were significantly lower than those at ambient temperature 22 degrees C. (2) Significant increases in core temperatures using two different warming equipments were observed at termination of TQ application and after TQ release at ambient temperature 20 degrees C. Core temperatures using air-forced warming were maintained during the investigation, though significant decrease in core temperature using active heated i.v. was recorded after TQ release. CONCLUSIONS: Air-forced warming maintains core temperature efficiently associated with lower extremity tourniquet.     

Follow-up for patients with obstructive sleep apnea syndrome using a portable recording device

A home screening device, LT-200, can record data on both breathing conditions and body positions during sleep for up to 3 consecutive days in patients with obstructive sleep apnea (OSAS). We investigated the usefulness of the LT-200 device for follow-up of OSAS. Eighteen patients (age 51.0 +/- 10.8 years, mean +/- SD) were enrolled in this study. Standard polysomnography (PSG) was performed on all patients. The number of apnea/hypopnea episodes per hour (apnea/hypopnea index: AHI), the total time that nocturnal oxygen saturation was < 90% (oxygen desaturation time: ODT), and the minimum oxygen saturation during sleep (lowest Spo2) were calculated. We used the LT-200 and PSG to evaluate any improvement in the data obtained after auto-continuous positive airway pressure (auto-CPAP) therapy. AHI was also measured using the LT-200 in three sleep positions to evaluate the efficacy of the lateral position. AHI, ODT, and lowest Spo2 values did not differ significantly between the PSG and LT-200 recordings on the control and therapy nights. The LT-200 recordings showed that AHI, ODT, and lowest Spo2 tended to be better on the second night of auto-CPAP therapy than on the first. AHI was significantly lower in the right and left lateral sleep positions than that in the supine position. Our findings suggest that since the LT-200 device provides important information about the severity of OSAS, the efficacy of auto-CPAP therapy, and body position under unattended conditions in the home. It may prove to be a useful tool for following up patients.     

Nasal resistance for determinant factor of nasal surgery in CPAP failure patients with obstructive sleep apnea syndrome

OBJECTIVES: Given that criteria for nasal surgery in individuals with obstructive sleep apnea syndrome (OSAS) have not been proposed, we investigated the effectiveness of nasal surgery for CPAP failure in patients with both severe OSAS and nasal obstruction. PATIENTS AND METHODS: Conventional nasal surgery was performed in 12 patients who were refractory to treatment by CPAP. The subject group consisted of 12 males (mean age, 54.2 +/- 9.2 years; range 39-66 years). The effect of nasal surgery was evaluated with data from preoperative and postoperative polysomunography. The nasal resistance value was first deduced to determine which OSAS patients with CPAP failure should undergo nasal surgery, compared to control values. RESULTS: Nasal surgery resulted in a significant decrease in nasal resistance, as measured by rhinomanometry, from 0.57 +/- 0.31 Pa/cm3 /sec to 0.16 +/- 0.03 Pa/cm3/sec and rendered all patients tolerant to CPAP. In addition, the lowest nocturnal oxygen saturation significantly increased from 68.3 +/- 12.1% to 75.3 +/- 7.1% after surgery. Subjectively, Epworth sleepiness scale (ESS) significantly decreased from 11.7 +/- 4.1 to 3.3 +/- 1.3 after surgery, but the number of apnea and hypopnea episodes per hour did not change significantly. In five patients, for whom it was possible to perform a CPAP titration before nasal surgery, the value decreased significantly from 16.8 +/- 1.1 to 12.0 +/- 1.9 cmH2O. The bilateral nasal resistance of the 410SAS patients with CPAP therapy (control group) was 0.24 +/- 0.11 Pa/cm3/sec. The cut off value for differentiation between CPAP failure patients and control group was determined as 0.38 Pa/cm3 /sec. CONCLUSION: Increased nasal resistance is a determinant of CPAP failure, and the surgical correction of severe nasal obstruction should thus be considered to facilitate treatment of OSAS patients with CPAP.