Diffraction-free acoustic detection for optoacoustic depth profiling of tissue using an optically transparent polyvinylidene fluoride pressure transducer operated in backward and forward mode

An optoacoustic detection method suitable for depth profiling of optical absorption of layered or continuously varying tissue structures is presented. Detection of thermoelastically induced pressure transients allows reconstruction of optical properties of the sample to a depth of several millimeters with a spatial resolution of 24 mum. Acoustic detection is performed using a specially designed piezoelectric transducer, which is transparent for optical radiation. Thus, ultrasonic signals can be recorded at the same position the tissue is illuminated. Because the optoacoustical sound source is placed in the pulsed-acoustic near field of the pressure sensor, signal distortions commonly associated with acoustical diffraction are eliminated. Therefore, the acoustic signals mimic exactly the depth profile of the absorbed energy. This is illustrated by imaging the absorption profile of a two-layered sample with different absorption coefficients, and of a dye distribution while diffusing into a gelatin phantom.     

T cell repertoire scanning is promoted by dynamic dendritic cell behavior and random T cell motility in the lymph node

Dendritic cells (DCs) ingest antigens in peripheral tissues and migrate to lymph nodes where they present MHC class II-bound antigen to CD4(+) T cells. We used two-photon microscopy to image the single-cell dynamics of interactions between DCs and T cells within intact lymph nodes in the absence of relevant antigen. DCs were fluorescently labeled in vivo by cutaneous injection of alum adjuvant including carboxyfluorescein diacetate succinimidyl ester (CFSE). CFSE-positive DCs (CD11c(+), CD11b(+), and low-to-intermediate CD8(+)) were observed in draining lymph nodes 24-72 h later. Labeled DCs meandered slowly (2-3 microm x min(-1)) in the T cell zone near B cell follicles but vigorously extended long agile dendrites. Encounters between T cells and DCs arose as T cells moved autonomously along random paths. Moreover, T cells did not accumulate around DCs, and their relative velocities approaching and departing DCs were equivalent, implying that T cells are not attracted toward DCs by chemotactic gradients but rather encounter them by chance. T cell/DC contacts occurred primarily on dendrites at arm's length from the DC soma and typically lasted approximately 3 min, enabling an individual DC to interact with up to 5000 T cells per hour. We conclude that dynamic DC gesticulation and random T cell motility together enhance the stochastic scanning of the T cell repertoire, thereby enabling rapid initiation of the immune response.     

Mass smallpox vaccination and cardiac deaths, New York City, 1947

In April 1947, during a smallpox outbreak in New York City (NYC), more than 6 million people were vaccinated. To determine whether vaccination increased cardiac death, we reviewed NYC death certificates for comparable periods in 1946, 1947, and 1948 (N = 81,529) and calculated adjusted relative death rates for the postvaccination period. No increases in cardiac deaths were observed.     

Pharmacology of the mouse-isolated cerebral artery

The routine availability of murine models of various cerebral circulatory disorders requires characterization of the regulation of cerebral artery tone in the mouse. Using vasoconstrictors and vasodilators with known efficacy in the cranial circulation of other species, we determined the pharmacological properties of the isolated pressurized mouse middle cerebral artery (MCA). The maximal pressure-induced myogenic constriction in isolated mouse MCA was 20.6+/-2.4%. Inhibition of nitric oxide (NO) and endothelin-1 (ET-1) altered the extent of pressure-induced myogenic tone. Isolated mouse MCA failed to either constrict or relax to 5-hydroxytryptamine (5-HT) and histamine; other vasoconstrictors demonstrated the following rank order of efficacy: ET-1>phenylephrine>U-46619. The rank order of endothelium-dependent vasodilator efficacy was bradykinin (BK)>acetylcholine (ACh)>substance P. The constriction produced by phenylephrine (PE) required a smaller increase in intracellular Ca(2+) elevation compared to constriction of a similar magnitude produced by membrane depolarization with potassium chloride (KCl). Pressure-induced myogenic tone (20-80 mm Hg) in mouse MCA was associated with smooth muscle cell membrane depolarization (-52.6+/-0.9 to -37.3+/-1.75 mV). Pressure-induced myogenic tone occurred with a smaller change in membrane potential compared to tone of a similar magnitude produced with KCl (-43.37+/-2.66 vs. -29.47+/-1.05 mV). The mouse MCA has a pharmacological profile that is distinct from other species including humans; however, similar to findings in other cerebral arteries, the mouse MCA shows intracellular sensitization to Ca(2+) following receptor activation.     

Radiolabeled antibody therapy in non-Hodgkins lymphoma: radiation protection, isotope comparisons and quality of life issues

Anti-CD20 antibodies radiolabeled with I-131 tositumomab (Bexxar) or Y-90-Ibritumomab tiuxetan (Zevalin), are similarly efficacious in treating chemotherapy-refractory non-Hodgkin's lymphoma. The relative merits of both radioimmunoconjugates with respect to practical issues, including radiation exposure risk, the advantages and disadvantages of the respective isotopes and other parameters that could affect a patient's quality of life are also important. I-131-labeled antibody treatment often requires inpatient hospitalization due to the inherent risk of exposure from gamma emissions, and patients and families should follow detailed instructions to prevent undue exposure. Other issues relevant to patients and medical staff include: (1) the need for dosimetry to calculate effective therapeutic doses of I-131-labeled anti-B1 (Bexxar) compared with the lack of correlation of dosimetry with marrow toxicity for IDEC-Y2B8 (Zevalin), (2) determining the acute and long-term toxic effects of each agent, (3) time commitments for nuclear medicine staff and patients along with the relative ease of administration, and (4) cost considerations. A more challenging future issue will be to determine the optimal use of Bexxar and Zevalin alone and in combination in ways that will significantly affect patient outcome without compromising quality of life. The recent demonstration of significant response rates in patients having chemotherapy-refractory Non-Hodgkin's Lymphoma (NHL) using both on I-131- and Y-90-labeled anti-CD20 antibodies with minimal toxicity has stimulated comparison of I-131 tositumomab (Bexxar) and Ibritumomab tiuxetan (Zevalin) in terms of radiation safety requirements, the advantages and disadvantages of both radionuclides, and quality-of-life (QOL) issues. Therefore, in this review, we attempt to compare the relative merits of (Bexxar and Zevalin) and address important practical considerations that may influence patient and physician choices regarding treatment using these agents.     

Unilateral decompressive craniectomy for children with severe brain injury. Report of seven cases and review of the relevant literature

Severe head injuries in children (under 15 years of age) have many features that differentiate them from head injuries in adults. In such cases, non-surgical treatment cannot always prevent fatal herniation. We report on seven cases of children with severe head injury, presenting with decorticate posturing and treated by unilateral decompressive craniectomy. The aim of the unilateral decompressive craniectomy was to decompress the midbrain and the brainstem. Post-operatively, all patients showed good recovery within 5 weeks (Glasgow Coma Scale score 15). The alternative treatment modalities are discussed critically in an attempt to determine the value of the unilateral decompressive craniectomy procedure and to define the clinical parameters that might identify those children most likely to benefit from this technique. CONCLUSION: the unilateral decompressive craniectomy has an advantage over non-surgical treatment of children with severe brain injury and should be considered in their management.     

Resistance-associated point mutations of organophosphate insensitive acetylcholinesterase,in the olive fruit fly Bactrocera oleae

A 2.2-kb full length cDNA containing an ORF encoding a putative acetylcholinesterase (AChE) precursor of 673 amino acid residues was obtained by a combined degenerate PCR and RACE strategy from an organophosphate-susceptible Bactrocera oleae strain. A comparison of cDNA sequences of individual insects from susceptible and resistant strains, coupled with an enzyme inhibition assay with omethoate, indicated a novel glycine-serine substitution (G488S), at an amino acid residue which is highly conserved across species (G396 of Torpedocalifornica AChE), as a likely cause of AChE insensitivity. This mutation was also associated with a 35-40% reduction in AChE catalytic efficiency. The I199V substitution, which confers low levels of resistance in Drosophila, was also present in B. oleae (I214V) and in combination with G488S produced up to a 16-fold decrease in insecticide sensitivity. This is the first agricultural pest where resistance has been associated with an alteration in AChE, which arises from point mutations located within the active site gorge of the enzyme.     

Dental implant treatment in diabetic patients

The purpose of the present study was twofold: (1) to investigate how many diabetic patients and types of cases that are treated with dental implants in our clinic; and (2) assess the outcome of such treatment. Medical records from 782 patients were examined in patients treated by the Br?nemark method for partial or total edentulism with implant supported bridges. From these records, 25 patients (3.2%) with diabetes before implant treatment (136 implants) were identified and further studied with respect to age, gender, type of diabetes, treated jaw, degree of edentulism, bone graft, implant survival, periimplant inflammation, bleeding on probing, and radiographic bone loss. Furthermore, the patients' opinion about the outcome of the treatment was registered. The implant success rate was 96.3% during the healing period and 94.1% 1 year after surgery. Of all 38 bridges, one was lost. Few complications occurred and all patients, except for one, were satisfied with the treatment. Today, diabetic patients are being treated successfully for all types of edentulism, including bone-grafting treatment. Diabetics that undergo dental implant treatment do not encounter a higher failure rate than the normal population, if the diabetics' plasma glucose level is normal or close to normal as assessed by personal interviews.     

Comparison of the effects of simultaneous administration of vitamin C and omega-3 fatty acids on lipoproteins,apo A-I,apo B,and malondialdehyde in hyperlipidemic patients

BACKGROUND: Control of hyperlipidemia is vital in patients with cardiovascular disease (CVD). Omega-3 fatty acids (n-3FAs) have desirable effects on serum triglyceride (TG) levels, thrombosis, and arrhythmia, but lead to increases in serum low-density lipoprotein (LDL) and apo-B as well. OBJECTIVE: To determine and compare the effects of administration of n-3FAs, vitamin C (VitC) and n-3FAs + VitC on the serum levels of LDL, apoB, other serum lipids, and malondialdehyde (MDA). The present study was performed in Tehran University of Medical Sciences from 2000 to 2001. DESIGN: In a double-blind, placebo trial of parallel design, 68 hyperlipidemic patients [total cholesterol (TC) and TG greater than 200 mg/dL] were randomly assigned to receive daily 500 mg VitC, 1 g n-3FAs, 500 mg VitC + 1 g n-3FAs, or placebo (control) for 10 weeks. Fasting blood samples were collected at the beginning and at the end of the period. TG, TC, LDL-cholesterol-C (LDL-C), and high-density lipoprotein-cholesterol (HDL-C) were measured enzymatically, VitC and MDA colorimetrically, and apo-B and apo-A-I immunoturbidometrically. The pattern of food consumption, socio-economic, and anthropometric indices were determined; there was no significant change in these indices during the study. RESULTS: There was a significant difference in the blood VitC level at the end of the study in comparison to the initial value in the VitC (p = 0.001) and VitC + n-3FAs (p = 0.027) groups. Similarly, the serum TG level at the end of study was significantly different from the initial value in the n-3FAs group (p = 0.002) and also from the final value in the control group (p = 0.013). In the VitC group, there was a significant decrease in TC (p = 0.004), apo-B (p = 0.005), and MDA (p = 0.015) at the end of study as compared to the respective initial values. There was also a significant increase in blood VitC compared to the control value (p = 0.018) and a significant decrease in MDA compared to the n-3FAs group (p = 0.034). At the end of study, in the n-3FAs group, there was a significant (p = 0.04) and a marginally significant decrease (p = 0.05), respectively, in TG/HDL and apo-B levels as compared to the initial values, and the TG/HDL ratio showed a significant decrease as compared to the control group (p = 0.047). CONCLUSION: Simultaneous administration of n-3FAs and VitC had no beneficial effects on the lipid profile of hyperlipidemic patients, but 1 g purified n-3FAs daily for 10 weeks is a beneficial supplement for decreasing TG without any increase in LDL-C, apo-B or MDA. Administration of 500 mg VitC for more than 10 weeks might decrease significantly TC and apo-B in hyperlipidemic patients.