Isolated right atrial appendage (RAA) rupture in blunt trauma – a case report and an anatomic study comparing RAA and right atrium (RA) wall thickness

Background  

Heart chambers rupture in blunt trauma is uncommon and is associated with a high mortality. The determinant factors, and the incidence of isolated heart chambers rupture remains undetermined. Isolated rupture of the right atrium appendage (RAA) is very rare, with 8 cases reported in the reviewed literature. The thin wall of the RAA has been presumed to render this chamber more prone to rupture in blunt trauma.     

Effects of interpleural bupivacaine (0.5%) on canine diaphragmatic function.

Several authors have questioned the potential for phrenic nerve paralysis with interpleural analgesia. This study was designed to examine the potential for phrenic nerve paralysis with the use of interpleural bupivacaine in dogs. Seven dogs were anesthetized, tracheally intubated, and allowed to breathe spontaneously with halothane/oxygen while in the supine position. After a midline laparotomy, two wires were inserted into the costal portion of each hemidiaphragm for measurement of electromyographic (EMG) signals. A balloon catheter was placed in the abdominal cavity to measure abdominal pressure. The abdomen was then closed. Airway pressure was measured through a side port in the endotracheal tube. Bilateral interpleural catheters were inserted with the loss-of-resistance technique. Each dog was used for two experiments, one on each side, except for one animal. To assess the contribution of the ipsilateral diaphragm to total respiratory effort, the airway was occluded at functional residual capacity for three consecutive breaths, and EMG, airway pressure, and abdominal pressure were measured. In five of nine experiments with bupivacaine, there was complete loss of EMG activity on the side of the injection. In two dogs, there was partial loss of diaphragmatic function, and in the remaining two, there was no change in EMG. In the normal saline solution group (n = 4), there was no change in the EMG. Two dogs that received bilateral bupivacaine injections developed paradoxical respiration with negative inspiratory intraabdominal pressures. Phrenic nerve paralysis or paresis can occur with interpleural blockade. The factors affecting the occurrence of this complication remain to be elucidated.     

Lack of c-kit (CD117) expression in CD30+ lymphomas and lymphomatoid papulosis.

c-Kit receptor (CD117) is expressed by erythroid, megakaryocytic, and myeloid precursors and mature mast cells and has been reported to be expressed in CD30+ lymphomas such as Hodgkin's disease and anaplastic large-cell lymphoma. Imatinib mesylate, a well-established inhibitor of bcr-abl tyrosine kinase, and currently used for the treatment of patients with chronic myeloid leukemia, also inhibits c-kit receptor kinase activity. In view of the possible use of imatinib as experimental therapy for patients with c-kit-positive tumors, we assessed c-kit expression in CD30+ cell lines and lymphomas. The cell lines were assessed using multiple methods (RT-PCR, flow cytometry, and Western blot). c-Kit expression was also immunohistochemically assessed in 168 CD30+ lymphomas including 87 classical Hodgkin's disease, 63 anaplastic large-cell lymphoma, and 15 cutaneous anaplastic large-cell lymphoma. We also studied 18 cases of lymphomatoid papulosis, a CD30+ lesion closely related to cutaneous anaplastic large-cell lymphoma. Neither c-kit mRNA nor protein was detected in any of the cell lines assessed. Furthermore, treatment with imatinib did not inhibit proliferation of cell lines in vitro. Using immunohistochemistry, only one of 183 (0.5%) lesions was positive for c-kit, the positive case being an ALK-negative anaplastic large-cell lymphoma. Our data demonstrate that expression of c-kit receptor is exceedingly rare among CD30+ lymphomas and lymphomatoid papulosis, suggesting that c-kit receptor is unlikely to be an appropriate target for therapeutic options such as imatinib in patients with these tumors.     

Hepatitis B vaccination and central nervous system demyelination: an immunological approach

Demyelination events or multiple sclerosis following hepatitis B virus (HBV) vaccination have been reported. We therefore compared the T-cell response to HBsAg in patients with CNS demyelination following HBV vaccination and in HBV-vaccinated healthy individuals. Our data showed no differences in terms of T-cell proliferation or cytokine production between these groups and may help to allay concerns that HBV vaccination might trigger a deleterious immune response.     

Involvement of the catecholaminergic system in glucagon-induced thermogenesis in Muscovy ducklings (Cairina moschata)

Physiological studies have shown that glucagon is a potential mediator of nonshivering thermogenesis (NST) in birds. The present work was undertaken in order to investigate whether the observed thermogenesis results from a direct action of glucagon on avian thermoregulatory mechanisms or in fact requires the participation of other agents such as catecholamines. Our experiments were performed using cold-acclimated (CA) ducklings which developed muscle NST. A comparison was made with thermoneutral (TN) ducklings of the same age. Our principal results showed that: (1) at ambient temperature (25 degrees C), circulating norepinephrine (NE) was markedly decreased in CA ducklings (-42%), while circulating epinephrine (E) did not undergo any consistent change; (2) in CA and TN ducklings, an intraperitoneal injection of glucagon (360 microg x kg(-1)) was followed after 10 min by prominent lipolysis and a large increase in circulating NE (4- to 6-fold) and E (14- to 17-fold), which was sustained for at least 1 h. The elevation of circulating NE was less pronounced in CA ducklings. The thermogenic action of glucagon in birds is probably indirect and involves at least the mobilization of lipids and sympatho-adrenal stimulation. The changes in peripheral noradrenergic activity during cold acclimation could be associated with adaptive changes leading to NST.     

Basement membrane thickening in the placentae from diabetic women

A light microscopy study was carried out on 48 placentae. Seventeen placentae were obtained from non-diabetic mothers while the other 31 placentae were from both women with controlled diabetes and women who had an abnormality of the glucose tolerance test. All the women delivered at 38-40 weeks of gestation. Placentae from diabetic patients showed immaturity of the villi, hypertrophy of the capillaries and thickening of the basement membrane of the trophoblastic villi (3.2 +/- 0.35 microns) and the amniotic membrane (1.8 +/- 0.3 microns). Focal fibrinoid necrosis, an increase in the number of Hofbauer cells and dilatation of villi capillaries were also commonly observed in placentae from diabetic mothers, and the normal cuboidal cells lining the amniotic membrane tended to become tall columnar (17.6 +/- 6.3 microns) with distally located nuclei. Similar findings were observed in patients who had a potentially abnormal glucose tolerance test, which suggests the possibility of primary lesion in origin. Therefore, control of hyperglycemia may only partially prevent the development of placental abnormalities.     

Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma.

PURPOSE: Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL. PATIENTS AND METHODS: Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 microg/kg once daily for 5 days every 3 weeks, up to eight cycles. RESULTS: Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25- histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient. CONCLUSION: Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25- B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted.     

Emerging applications of the tumor necrosis factor family of ligands and receptors in cancer therapy.

Abnormalities of the tumor necrosis factor (TNF) family members have been linked to several human diseases, including cancer. Novel treatment strategies for cancer are emerging based on an understanding of the function of TNF family members. The advantage of these strategies is their potential to selectively target cancer cells, while sparing normal cells. Combining these new strategies with currently available treatments such as chemotherapy and radiation therapy is under investigation, with promising results. However, because some TNF family members are toxic to normal mammalian cells when administered systemically, only a few TNF family members have potential therapeutic value. This concise review focuses on the clinical implications of four TNF family members for cancer treatment: CD30/CD30 ligand, CD40/CD40 ligand, receptor activator of nuclear factor-kappaB (RANK)/RANK ligand, and TNF-related apoptosis-inducing ligand (TRAIL) Apo-2L/TRAIL receptors.     

Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma.

PURPOSE: Evaluate efficacy and toxicity of bortezomib in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients were stratified, based on preclinical data, into arm A (mantle-cell lymphoma) or arm B (other B-cell lymphomas) without limitation in number of prior therapies. Bortezomib was administered as an intravenous push (1.5 mg/m2) on days 1, 4, 8, and 11 every 21 days for a maximum of six cycles. RESULTS: Sixty patients with a median number of prior therapies of 3.5 (range, one to 12 therapies) were enrolled; 33 patients were in arm A and 27 were in arm B, including 12 diffuse large B-cell lymphomas, five follicular lymphomas (FL), three transformed FLs, four small lymphocytic lymphomas (SLL), two Waldenstrom's macroglobulinemias (WM), and one marginal zone lymphoma. In arm A, 12 of 29 assessable patients responded (six complete responses [CR] and six partial responses [PR]) for an overall response rate (ORR) of 41% (95% CI, 24% to 61%), and a median time to progression not reached yet, with a median follow-up of 9.3 months (range, 1.7 to 24 months). In arm B, four of 21 assessable patients responded (one SLL patient had a CR, one FL patient had a CR unconfirmed, one diffuse large B-cell lymphoma patient had a PR, and one WM patient had a PR) for an ORR of 19% (95% CI, 5% to 42%). Grade 3 toxicity included thrombocytopenia (47%), gastrointestinal (20%), fatigue (13%), neutropenia (10%), and peripheral neuropathy (5%). Grade 4 toxicity occurred in nine patients (15%), and three deaths from progression of disease occurred within 30 days of withdrawal from study. CONCLUSION: Bortezomib showed promising activity in relapsed mantle-cell lymphoma and encouraging results in other B-cell lymphomas. Future studies will explore bortezomib in combination with other cytotoxic or biologic agents.     

Sleep architecture based on sleep depth and propensity: patterns in different demographics and sleep disorders and association with health outcomes

Study ObjectivesConventional metrics of sleep quantity/depth have serious shortcomings. Odds-Ratio-Product (ORP) is a continuous metric of sleep depth ranging from 0 (very deep sleep) to 2.5 (full-wakefulness). We describe an ORP-based approach that provides information on sleep disorders not apparent from traditional metrics.MethodsWe analyzed records from the Sleep-Heart-Health-Study and a study of performance deficit following sleep deprivation. ORP of all 30-second epochs in each PSG and percent of epochs in each decile of ORPs range were calculated. Percentage of epochs in deep sleep (ORP < 0.50) and in full-wakefulness (ORP > 2.25) were each assigned a rank, 1–3, representing first and second digits, respectively, of nine distinct types (“1,1”, “1,2” … ”3,3”). Prevalence of each type in clinical groups and their associations with demographics, sleepiness (Epworth-Sleepiness-Scale, ESS) and quality of life (QOL; Short-Form-Health-Survey-36) were determined.ResultsThree types (“1,1”, “1,2”, “1,3”) were prevalent in OSA and were associated with reduced QOL. Two (“1,3” and “2,3”) were prevalent in insomnia with short-sleep-duration (insomnia-SSD), but only “1,3” was associated with poor sleep depth and reduced QOL, suggesting two phenotypes in insomnia-SSD. ESS was high in types “1,1” and “1,2”, and low in “1,3” and “2,3”. Prevalence of some types increased with age while in others it decreased. Other types were either rare (“1,1” and “3,3”) or high (“2,2”) at all ages.ConclusionsThe proposed ORP histogram offers specific and unique information on the underlying neurophysiological characteristics of sleep disorders not captured by routine metrics, with potential of advancing diagnosis and management of these disorders.