Fluorescence tomographic imaging in turbid media using early-arriving photons and Laplace transforms

We present a multichannel tomographic technique to detect fluorescent objects embedded in thick (6.4 cm) tissue-like turbid media using early-arriving photons. The experiments use picosecond laser pulses and a streak camera with single photon counting capability to provide short time resolution and high signal-to-noise ratio. The tomographic algorithm is based on the Laplace transform of an analytical diffusion approximation of the photon migration process and provides excellent agreement between the actual positions of the fluorescent objects and the experimental estimates. Submillimeter localization accuracy and 4- to 5-mm resolution are demonstrated. Moreover, objects can be accurately localized when fluorescence background is present. The results show the feasibility of using early-arriving photons to image fluorescent objects embedded in a turbid medium and its potential in clinical applications such as breast tumor detection.     

Coexisting Normal Sinus Rhythm and Atrial Fibrillation 18 Years after Heart Transplant

Abstract Atrial fibrillation is an important cardiogenic cause of embolic phenomenon to the brain leading to stroke and long‐term disability. Recognition of atrial fibrillation is of cardinal importance in the workup of stroke and transient ischemic attack (to prevent future strokes) by the timely institution of anticoagulation therapy. We describe a patient with history of standard orthotopic heart transplant (st.OHT) who had no clinical or electrocardiographic signs of atrial fibrillation. He presented with a transient ischemic attack (TIA) and subsequently was found to have two distinct left atrial appendages (LAA) in two different rhythms based on transesophageal echocardiography (TEE) and pulse wave (PW) Doppler. The donor LAA was in normal sinus rhythm (NSR) and recipient LAA in atrial fibrillation (AF). This was an extremely rare but important diagnosis in our patient, which led to the institution of anticoagulation therapy rather than aspirin and dipyramidole as described in neurological literature. We discuss different types of heart transplant techniques and their causatum on postoperative atrial tachycardias. Significance of TEE in the scenario of TIA and follow‐up in heart transplant patients is also canvassed.     

A rare case of seronegative culture--proven infection with Brucella suis

Brucellosis is a chronic infection produced by members of the Brucella family. Diagnosis of this condition requires either isolation of the organism in culture or positive serological tests.We describe a 27-year-old male admitted as a case of pyrexia of unknown origin (PUO), who tested negative for Brucella IgM ELISA test on preliminary evaluation but was subsequently diagnosed on the strength of positive blood and bone marrow cultures to be a case of brucellosis secondary to Brucella suis infection. In addition to highlighting the pathogenic potential of an unusual organism, this case demonstrates the unreliability of standard serological tests based on the Brucella melitensis antigen for infection with other species of Brucella.     

Rapid and accurate determination of tissue optical properties using least-squares support vector machines

Diffuse reflectance spectroscopy (DRS) has been extensively applied for the characterization of biological tissue, especially for dysplasia and cancer detection, by determination of the tissue optical properties. A major challenge in performing routine clinical diagnosis lies in the extraction of the relevant parameters, especially at high absorption levels typically observed in cancerous tissue. Here, we present a new least-squares support vector machine (LS-SVM) based regression algorithm for rapid and accurate determination of the absorption and scattering properties. Using physical tissue models, we demonstrate that the proposed method can be implemented more than two orders of magnitude faster than the state-of-the-art approaches while providing better prediction accuracy. Our results show that the proposed regression method has great potential for clinical applications including in tissue scanners for cancer margin assessment, where rapid quantification of optical properties is critical to the performance.     

Digestive vacuoles of Plasmodium falciparum are selectively phagocytosed by and impair killing function of polymorphonuclear leukocytes

Sequestration of parasitized erythrocytes and dysregulation of the coagulation and complement system are hallmarks of severe Plasmodium falciparum malaria. A link between these events emerged through the discovery that the parasite digestive vacuole (DV), which is released together with infective merozoites into the bloodstream, dually activates the intrinsic clotting and alternative complement pathway. Complement attack occurs exclusively on the membrane of the DVs, and the question followed whether DVs might be marked for uptake by polymorphonuclear granulocytes (PMNs). We report that DVs are indeed rapidly phagocytosed by PMNs after schizont rupture in active human serum. Uptake of malaria pigment requires an intact DV membrane and does not occur when the pigment is extracted from the organelle. Merozoites are not opsonized and escape phagocytosis in nonimmune serum. Antimalarial Abs mediate some uptake of the parasites, but to an extent that is not sufficient to markedly reduce reinvasion rates. Phagocytosis of DVs induces a vigorous respiratory burst that drives the cells into a state of functional exhaustion, blunting the production of reactive oxygen species (ROS) and microbicidal activity upon challenge with bacterial pathogens. Systemic overloading of PMNs with DVs may contribute to the enhanced susceptibility of patients with severe malaria toward invasive bacterial infections.     

Abdominal aortic aneurysms (AAA) post heart transplantation: a systematic review of literature

Peripheral vascular disease is highly prevalent post heart transplantation (HTx). The prevalence of abdominal aortic aneurysms (AAA) post HTx ranges from 1.1-10%. We performed a Pub Med, EMBASE and Cochrane review search to identify articles on AAA post HTx. Data gathered from published data included: risk factors, progression of the aneurysm and clinical outcomes. Five studies were included in the systematic review. Baseline demographic data, clinical characteristics, data on AAA prevalence and characteristics, the treatment strategies and follow up were extracted from each of these studies. Our systematic review showed that the prevalence of AAA post HTx ranged from 2-10% in the retrospective studies and 6.5% in a single prospective study. Rupture rates during a follow up period ranged from 11-38% and during that time period the mean aneurysmal expansion rate ranged from 0.78±0.41 cm/yr to 1.2±0.4 cm/yr. Male gender, ischemic heart disease, corticosteroid use, smoking and improved hemodynamics and ejection fraction post HTx were reported as possible associated risk factors in the development of AAA. Open surgical management was the treatment of choice although endovascular treatment was used in a minority of patients. AAA is increasingly prevalent post HTx and may be associated with greater rupture and expansion rates. Meticulous follow up and further prospective clinical studies are warranted to determine risk factors, expansion rates and clinical outcomes.     

Axonal remyelination by cord blood stem cells after spinal cord injury

Human umbilical cord blood stem cells (hUCB) hold great promise for therapeutic repair after spinal cord injury (SCI). Here, we present our preliminary investigations on axonal remyelination of injured spinal cord by transplanted hUCB. Adult male rats were subjected to moderate SCI using NYU Impactor, and hUCB were grafted into the site of injury one week after SCI. Immunohistochemical data provides evidence of differentiation of hUCB into several neural phenotypes including neurons, oligodendrocytes and astrocytes. Ultrastructural analysis of axons reveals that hUCB form morphologically normal appearing myelin sheaths around axons in the injured areas of spinal cord. Colocalization studies prove that oligodendrocytes derived from hUCB secrete neurotrophic hormones neurotrophin-3 (NT3) and brain-derived neurotrophic factor (BDNF). Cord blood stem cells aid in the synthesis of myelin basic protein (MBP) and proteolipid protein (PLP) of myelin in the injured areas, thereby facilitating the process of remyelination. Elevated levels of mRNA expression were observed for NT3, BDNF, MBP and PLP in hUCB-treated rats as revealed by fluorescent in situ hybridization (FISH) analysis. Recovery of hind limb locomotor function was also significantly enhanced in the hUCB-treated rats based on Basso-Beattie-Bresnahan (BBB) scores assessed 14 days after transplantation. These findings demonstrate that hUCB, when transplanted into the spinal cord 7 days after weight-drop injury, survive for at least 2 weeks, differentiate into oligodendrocytes and neurons, and enable improved locomotor function. Therefore, hUCB facilitate functional recovery after moderate SCI and may prove to be a useful therapeutic strategy to repair the injured spinal cord.     

In vivo methylmercury exposure induced long-lasting epileptiform activity in layer II/III neurons in cortical slices from the rat

Prenatal and postnatal methylmercury (MeHg) exposure has been shown to increase neuronal excitability and seizure susceptibility. To determine if early postnatal MeHg exposure causes a similar effect, we examined changes in field potentials in layer II/III neurons in cortical slices of rat following in vivo MeHg treatment. Rats received 0 (0.9% NaCl), 0.75 mg/kg/day or 1.5 mg/kg/day MeHg subcutaneously for 15 or 30 days beginning on postnatal day 5, after which cortical slices were prepared for field potential recordings. In slices from rats treated with vehicle, single pulse stimulation of layer IV of cortical slices induced a typical field excitatory postsynaptic potential (fEPSP) with a single spike. This type of fEPSPs was also seen in slices from rats with 15 day treatment with 0.75 mg/kg/day or 1.5 mg/kg/day MeHg. However, 30-day treatment with either MeHg dose resulted in fEPSPs with multiple spikes (epileptiform activity) in 40% of animals examined. This epileptiform activity remained observable in 50–60% animals in which MeHg exposure had been terminated for 30 days. However, slices from control animals still showed fEPSPs with single spike. Thus, these data suggest that postnatal MeHg exposure in vivo altered neuronal excitability and induced a long-lasting hyperexcitability in cortical neurons.