Positional sleep apnea in patients with ischemic stroke

BACKGROUND: In non-stroke patients, the severity of sleep apnea (SA) is known to be frequently related to the sleeping position, a condition called positional SA. In the present study, we investigated whether in acute stroke the occurrence of apneas was related to the positioning of patients, and whether a similar finding could be observed after rehabilitation. With the purpose of identifying patients potentially being in need of a SA treatment beyond rehabilitation, we furthermore looked for epidemiologic and clinical parameters being related to persistent SA 6 months after stroke. PATIENTS AND METHODS: Fifty-five acute stroke patients underwent cardiorespiratory polygraphy within 72 hours after onset of neurological symptoms and after 6 months. Apart from the total AHI (AHITOT), the AHI with the patient in supine position and the AHI with the patient in other positions were determined. In all patients, demographic data, NIH-stroke scale score and cumulative vascular risk factors were assessed. RESULTS: In the initial sleep study, 78% of patients had an AHI>or=10/h, of whom 65% fulfilled the criteria of positional SA. On follow-up, the incidence of SA declined to 49% with positional SA being present in 33%. Multivariate logistic regression analysis identified AHITOT on admission [OR=1.07 (1.002-1.13)] and cumulative vascular risk factors [OR=3.48 (1.34-9.05)] as independent predictors of persistent SA 6 months after stroke. CONCLUSION: According to our results, positional SA is a predominant feature in acute stroke and its incidence decreases significantly during the following months. These findings may have implications for SA treatment in patients with acute stroke.     

In vitro resistance of articular chondrocytes to 5-Aminolevulinic acid based photodynamic therapy

OBJECTIVE: 5-Aminolevulinic acid based photodynamic therapy (5-ALA-PDT) has revealed promising results in the treatment of inflammatory joint diseases due to the sensitivity of inflamed synovial tissue. For 5-ALA-PDT to be safe and beneficial for intra-articular applications, resistance of chondrocytes is essential to prevent cartilage damage. As no data yet exist, the aim of the present study was to assess in vitro the response of the chondrocytes to 5-ALA-PDT and to compare with osteoblasts and synovial tissue derived cells. METHODS: Bovine articular chondrocytes, osteoblasts, and synovial cells were subjected to 5-ALA-PDT in cell culture. The PpIX accumulation and the function of the cells were assessed for up to 12 days. RESULTS: Bovine chondrocytes showed lower PpIX fluorescence upon incubation with 5-ALA (0.0-2.0 mM) for 4 hours as compared to osteoblasts and synovial cells suggesting a low PpIX accumulation. After incubation with 0.5 mM 5-ALA and application of light at a dose of 20 J/cm2, chondrocytes were functionally not affected (collagen type II and aggrecan mRNA, glycosaminoglycan synthesis) whereas a decrease in the proportion of viable cells was observed in osteoblasts and synovial cells (2+/-2% and 14+/-8%, respectively; chondrocytes 91+/-13%). Chondrocytes showed a 58% reduction of 5-ALA uptake using [3H]5-ALA as compared to osteoblasts and a lower mitochondrial content as assessed by the activity of the mitochondrial marker enzyme citrate synthase (9.2+/- 3.6 mU/mg protein) than osteoblasts (32.6+/-10.5 mU/mg) and synovial cells (60.0+/-10.8 mU/mg). The reduced uptake of 5-ALA and/or the low mitochondrial content, an adaptation to their in vivo environment and the site of PpIX synthesis, presumably explains the lower PpIX content in chondrocytes and their resistance against 5-ALA-PDT. CONCLUSION: 5-ALA-PDT might represent a treatment strategy in inflammatory joint diseases without endangering the cartilage function. However, further in vitro and in vivo experiments are required to confirm this data in the authentic environment of chondrocytes, the articular cartilage.     

Celiac artery thrombosis in a young patient with multiple platelet receptor polymorphisms and local compression syndrome

Numerous clinical and experimental studies have been published concerning platelet receptor polymorphism and their role in causing myocardial infarction at an earlier age. It is still unclear, however, whether these polymorphisms are a risk factor for other occlusive diseases such as those in visceral arteries. We report a case of a young woman with acute celiac artery thrombosis and multiple platelet receptor polymorphisms. In addition, the intraoperative exploration showed some evidence of a local vascular compression syndrome. The patient was successfully treated with a bypass procedure and combined anticoagulation. It seems that platelet receptor polymorphisms are a moderate risk factor for local artery thrombosis regardless of vascular region. The obligatory precondition is pre-existing vascular damage, such as that caused by a local compression syndrome.     

A stereotactic device for rabbits based on mandibular and cranial landmarks: technical note

The authors have developed a stereotactic device for use in rabbits that uses the plane at the base of the mandible combined with cranial sutures as an anatomical reference. The device was developed for a study designed to evaluate catheters for infection prophylaxis, and this required the implantation of silicone catheters along a reproducible trajectory through the lateral ventricle. Cadaver and atlas studies demonstrated consistent spatial relationships between intracranial structures and the surface plane on which the animals were resting during the surgery. This plane is formed by the 2 mandibular angles and the mandibular tip. The authors developed a stainless steel stereotactic device that uses this mandibular plane as well as the coronal and sagittal sutures as spatial references. Operations were performed in 60 animals using the stereotactic device, and postmortem dissections of the animals' brains demonstrated 78.6% accuracy of the trajectory within a tolerance of deviation of 5 degrees , and 94.6% accuracy within a tolerance of 10 degrees . The accuracy of the trajectory of the last 18 consecutively operated animals was constantly within a tolerance of 5 degrees . The device can be autoclaved and, since it is relatively simple and inexpensive to build, the authors manufactured 3 identical frames and used them alternately to operate under sterile conditions. The fast and pain-free head fixation minimized anesthesia-related risks. The authors' experiences suggest that the device is suitable for ventricular punctures and, dependant on the individual requirements of accuracy, other procedures that require "approximate" stereotactic guidance especially when a series of animals need to undergo operations quickly.     

Over 500 solitary pancreas transplants in nonuremic patients with brittle diabetes mellitus

BACKGROUND: A pancreas transplant alone (PTA) in a nonuremic patient with brittle diabetes mellitus remains a rare procedure because the tradeoff for insulin independence is lifelong immunosuppression. METHODS: Herein we report our results at the University of Minnesota of 513 PTAs from December 17, 1966, through December 31, 2006. Of these recipients, 87% had previously experienced hypoglycemic unawareness and 23% experienced coma and/or seizures. These transplants spanned four immunosuppressive eras: pre-cyclosporine A (pre-CsA) era (16%), CsA era (23%), tacrolimus (TAC) era (47%), and calcineurin-inhibitor (CNI)-free era (14%). RESULTS: The overall patient survival rate at 1 year posttransplant was about 95%; at 5 years, it was 90%. The pancreas graft survival rate at 1 year increased significantly from the pre-CsA era (31%) to the TAC era (75%), thanks to a significant decline in immunologic and technical failures. The CNI-free protocol, because of its high infection and hematologic infection rate, did not further improve outcome. Risk factors for subsequent kidney failure (13% at 5 years posttransplant) were serum creatinine levels>1.5 mg/dl at the time of the pancreas transplant and recipient age<30 years. CONCLUSIONS: A technically successful PTA is currently the only treatment option that allows nonuremic patients with brittle diabetes to become insulin-independent in the long term.     

Accelerated partial breast irradiation: consensus statement of 3 German Oncology societies

BACKGROUND: Breast-conserving surgery followed by whole-breast radiotherapy (WBRT) has become the standard treatment for the majority of patients with early breast cancer. Whereas the indications for systemic adjuvant treatment have continuously expanded, there is a tendency to restrict postoperative radiotherapy to accelerated partial breast irradiation (APBI) instead of WBRT. METHODS: The different techniques of APBI are described and their respective advantages or potential drawbacks outlined. Moreover, the results described in the literature are briefly reviewed as a basis for the consensus statements and recommendations of the German Society of Radiation Oncology, the German Society of Senology, and the Working Group for Gynecological Oncology of the German Cancer Society. RESULTS: The methods mainly used for APBI are: interstitial radiotherapy with multicatheter technique, intraoperative radiotherapy (IORT) using either electrons produced by linear accelerators or 50 kV x-rays (Intrabeam), the balloon-catheter technique (MammoSite), or 3D conformal external beam radiotherapy. These techniques have marked differences in dose distribution and homogeneity. The published range of local recurrence rates varies between 0% to 37%, the median follow-up from 8 to 72 months. CONCLUSIONS: To date, follow-up times mostly do not yet permit a definite judgment concerning the long-term effectiveness and side effects of APBI. The relevant societies in Germany support randomized clinical studies comparing APBI with WBRT in a well-defined subset of low-risk patients. However, the authors expressly discourage the routine use of APBI outside clinical trials. Until definite results show that APBI neither impairs therapeutic outcome nor cosmetic results, WBRT remains the gold standard in the treatment of early breast cancer.     

Intensive chemotherapy is not recommended for patients aged >60 years who have myelodysplastic syndromes or acute myeloid leukemia with high-risk karyotypes

BACKGROUND: It is unclear whether intensive chemotherapy is beneficial to patients with high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) if they are aged >/=60 years. METHODS: The authors studied 160 patients with a median age of 67 years who received intensive chemotherapy for MDS or AML with cytosine arabinoside and an anthracycline. RESULTS: At diagnosis, cytogenetic analysis was available in 146 patients. Karyotype was normal in 78 patients and abnormal in 68 patients. Of the abnormal karyotypes, 32 belonged to the high-risk category, ie, they involved either >/=3 chromosomes or chromosome 7. Complete remission (CR) was achieved by 94 patients (56%). CR rates were 70% among the patients who had a normal karyotype, 69% among the patients who had an abnormal (noncomplex) karyotype, but only 46% among the patients ho had a high-risk karyotype. The median survival was 9.5 months in the entire group, 18 months in patients with normal karyotype, 6 months in patients with abnormal, and 4 months in patients with a high-risk karyotype. A poor prognosis was attributable to low rates of CR and a high risk of early recurrence. CONCLUSIONS: According to the current data, elderly patients with AML or advanced MDS do not benefit from intensive chemotherapy if they show karyotype anomalies, especially those in the high-risk category.     

Individualized estimates of second cancer risks after contemporary radiation therapy for Hodgkin lymphoma

BACKGROUND: Estimates of radiation-related second cancer risk among Hodgkin lymphoma survivors are largely based on radiation therapy (RT) fields and doses no longer in use, and these estimates do not account for differences in normal tissue dose among individual patients. This study gives individualized estimates for the risks of lung and female breast cancer expected with contemporary involved-field RT and low-dose (20 Gy) RT for mediastinal Hodgkin lymphoma. METHODS: Three RT plans were constructed for 37 consecutive patients with mediastinal Hodgkin lymphoma: 35 Gy mantle RT, 35 Gy involved-field RT (IFRT), and 20 Gy IFRT. For each of the 111 RT plans, individual-level dosimetry data were incorporated into a cell initiation/inactivation/proliferation model to estimate the excess relative risk (ERR) and cumulative incidence of radiation-induced second cancer. RESULTS: ERR estimates were compatible with results of epidemiological studies. Compared with 35 Gy mantle radiation therapy, 35 Gy IFRT was predicted to reduce the 20-year ERRs of breast and lung cancer by 63% and 21%, respectively, primarily because of lower normal tissue doses with the omission of axillary RT. Low-dose (20 Gy) IFRT was associated with a 77% and 57% decrease in these ERRs. Patient-specific differences in normal tissue dose with IFRT led to 11-fold and 3.6-fold variations among individual's estimates of breast and lung cancer ERR, respectively. CONCLUSIONS: Contemporary IFRT is predicted to substantially reduce risk of secondary breast and lung cancer compared with mantle RT, with considerable variation in risk among individuals. Individualized prospective risk estimates could facilitate patient-specific counseling and the development of more effective RT techniques.     

Loss of programmed cell death 4 expression marks adenoma-carcinoma transition, correlates inversely with phosphorylated protein kinase B, and is an independent prognostic factor in resected colorectal cancer

BACKGROUND: Programmed cell death 4 (Pdcd4) inhibits malignant transformation, and initial studies of Pdcd4 suggested the regulation of Pdcd4 localization by protein kinase B (Akt). However, supporting patient tissue data are missing, and the diagnostic/prognostic potential of Pdcd4 rarely has been studied. The objectives of the current were 1) to determine Pdcd4 as a diagnostic marker in the adenoma-carcinoma sequence, 2) to support phosphorylated Akt (pAkt)-mediated Pdcd4 regulation in vivo, and 3) to obtain the first prognostic evidence of Pdcd4 in colorectal cancer. METHODS: Tumor samples and normal tissues from 71 patients with colorectal cancer who were followed prospectively (median follow-up, 36 months) and 42 adenomas were analyzed for Pdcd4, Akt, and pAkt in immunohistochemical and Western blot analyses. RESULTS: A significant reduction in Pdcd4 was observed between normal mucosa and adenomas and between adenomas and tumor samples (P < .01 and P < .01, respectively). Normal mucosa demonstrated strong nuclear Pdcd4, which was reduced significantly in adenomas (P < .01) and almost was lost in tumors (P < .01). pAkt was correlated inversely with Pdcd4 and with the transition of Pdcd4 from nucleus to cytoplasm (P < .01). Kaplan-Meier analysis (using the Mantel-Cox log-rank test) indicated a significant correlation between the loss of total and nuclear Pdcd4 in tumors and overall survival (P < .05 and P < .02, respectively) and disease-specific survival (P < .01 and P < .01, respectively). In multivariate analysis, loss of total or nuclear Pdcd4 was an independent predictor of disease-specific or overall survival. CONCLUSIONS: To the authors' knowledge, this is the first study to demonstrate an independent prognostic impact of Pdcd4 and its expression pattern in colorectal cancer. Data from this study support the regulation of Pdcd4 localization by pAkt in vivo. Pdcd4 immunohistochemistry may be useful as a supportive diagnostic tool for the transition between normal, adenoma, and tumor tissues.