Design of a handheld optical coherence microscopy endoscope

Optical coherence microscopy (OCM) combines coherence gating, high numerical aperture optics, and a fiber-core pinhole to provide high axial and lateral resolution with relatively large depth of imaging. We present a handheld rigid OCM endoscope designed for small animal surgical imaging, with a 6-mm diam tip, 1-mm scan width, and 1-mm imaging depth. X-Y scanning is performed distally with mirrors mounted to micro galvonometer scanners incorporated into the endoscope handle. The endoscope optical design consists of scanning doublets, an afocal Hopkins relay lens system, a 0.4 numerical aperture water immersion objective, and a cover glass. This endoscope can resolve laterally a 1.4-μm line pair feature and has an axial resolution (full width half maximum) of 5.4 μm. Images taken with this endoscope of fresh ex-vivo mouse ovaries show structural features, such as corpus luteum, primary follicles, growing follicles, and fallopian tubes. This rigid handheld OCM endoscope can be useful for a variety of minimally invasive and surgical imaging applications.     

Immunomodulation by ultraviolet light: clinical studies and biological effects

The interest o f immunologists in ultraviolet (UV) irradiation stems from observations made in vitro and in vivo. In vitro, UV irradiation inhibits mitogen and mixed lymphocyte culture (MLC) responses and in vivo, it can induce cutaneous anergy, apparently via suppressor cells and serum factors. At present much interest is focused on the possible use o f UV irradiation to permit transfusion without allosensitization and transplantation without either rejection or graft-versus-host disease (GVHD). Here, Derwood Pamphilon and colleagues discuss the current uses and potential o f UV irradiation in transfusion and transplantation and relate these to experimental evidence on its effects at the cellular level.     

Design and tests of a portable mini gamma camera

Design optimization, manufacturing, and tests, both laboratory and clinical, of a portable gamma camera for medical applications are presented. This camera, based on a continuous scintillation crystal and a position-sensitive photomultiplier tube, has an intrinsic spatial resolution of approximately 2 mm, an energy resolution of 13% at 140 keV, and linearities of 0.28 mm (absolute) and 0.15 mm (differential), with a useful field of view of 4.6 cm diameter. Our camera can image small organs with high efficiency and so it can address the demand for devices of specific clinical applications like thyroid and sentinel node scintigraphy as well as scintimammography and radio-guided surgery. The main advantages of the gamma camera with respect to those previously reported in the literature are high portability, low cost, and weight (2 kg), with no significant loss of sensitivity and spatial resolution. All the electronic components are packed inside the minigamma camera, and no external electronic devices are required. The camera is only connected through the universal serial bus port to a portable personal computer (PC), where a specific software allows to control both the camera parameters and the measuring process, by displaying on the PC the acquired image on "real time." In this article, we present the camera and describe the procedures that have led us to choose its configuration. Laboratory and clinical tests are presented together with diagnostic capabilities of the gamma camera.     

Transmission of polarized light in skeletal muscle

Experiments were conducted to study polarized light transmission in fresh bovine skeletal muscle of varying thicknesses. Two-dimensional polarization-sensitive transmission images were acquired and analyzed using a numerical parametric fitting algorithm. The total transmittance intensity and degree-of-polarization were calculated for both central ballistic and surrounding scattering regions. Full Mueller matrix images were derived from the raw polarization images and the polar decomposition algorithm was applied to extract polarization parameters. The results suggest that polarized light propagation through skeletal muscle is affected by strong birefringence, diattenuation, multiple scattering induced depolarization and the sarcomere diffraction effect.     

Best practices for clinical pathology testing in carcinogenicity studies

The Society of Toxicologic Pathology (STP) and American Society for Veterinary Clinical Pathology (ASCVP) convened a Clinical Pathology in Carcinogenicity Studies Working Group to recommend best practices for inclusion of clinical pathology testing in carcinogenicity studies. Regulatory guidance documents and literature were reviewed, and veterinary pathologists from North America, Japan, and Europe were surveyed regarding current practices, perceived value, and recommendations for clinical pathology testing in carcinogenicity studies. For two-year rodent carcinogenicity studies, the Working Group recommends that clinical pathology testing be limited to collection of blood smears at scheduled and unscheduled sacrifices to be examined only if indicated to aid in the diagnosis of possible hematopoietic neoplasia following histopathologic evaluation. Additional clinical pathology testing is most appropriately used to address specific issues from prior toxicity studies or known test article-related class effects. Inadequate data were available to make a recommendation concerning clinical pathology testing for alternative six-month carcinogenicity assays using genetically modified mice, although the Working Group suggests that it may be appropriate to use the same approach as for two-year carcinogenicity studies since the study goal is the same.     

Design and evaluation of a handheld impedance plethysmograph for measuring heart rate variability

Heart rate variability (HRV) analysis from 10s ECGs has been shown to be reliable. However, the short examination time warrants a user-friendly system that can be used forad-hoc examinations without normal preparation, unlike ECG. A handheld device has been developed that can measure ultra-short HRV from impedance plethysmographic recordings of the pulse wave in distal superficial arteries. The prototype device was made user-friendly through a compact, pen-like design and the use of integrated metal electrodes that were especially designed for dry operation. The main signal processing was performed by a digital signal processor, where the discrete heart beats were detected using a correlation algorithm that could adapt to individual pulse wave shapes to account for biological variation. The novel device was evaluated in 20 mainly young volunteers, using 10 s time-correlated ECG recordings as the reference method. Agreement between the two methods in measuring heart rate and root mean square of successive differences in the heart beat interval (RMSSD) was analysed using correlation coefficients (Pearson's R²), mean differences with 95% confidence intervals and 95% limits of agreement, and Bland-Altman plots. The correlation between the two methods was R²=1.00 and R²=0.99 when heart rate and RMSSD were measured, respectively. The Bland-Altman plots showed suitable agreement between the novel device and standard 10 s ECGs, which was substantiated by 95% limits of agreement of the difference of ± 0.1 beats min⁻¹ and ∼ ± 10 ms for heart rate and RMSSD, respectively. Therefore the evaluation showed no significant systematic error of the novel device compared with ECG.     

International harmonisation of clinical pathology testing for non-clinical toxicity and safety studies

International harmonisation of safety testing is currently of interest to industries and government agencies involved in the development and regulation of new drugs, chemicals, food products, and biological devices in global markets. A special meeting of an international working group representing ten professional scientific organisations involved primarily with clinical pathology testing in non-clinical toxicity and safety studies was held on conjunction with the 1993 European Comparative Clinical Pathology meeting in Nottingham, England. Delegates representing professional scientific organisations from the United States, United Kingdom, Japan, Germany, France, Italy, Israel, Canada, Sweden, and The Netherland have agreed to use the published testing recommendations of the American Association of Clinical Chemistry's Division of Animal Clinical Chemistry and the American Society of Veterinary Clinical Pathology as a starting point for scientific discussion and the development of internationally harmonised testing recommendations. Approximately 80 written revision proposals were reviewed and discussed. Technical issues that generated significant discussion included blood sampling protocols, urinalysis testing, and statistical analysis of clinical pathology data. A voting procedure was defined for resolution of technical issues. Final recommendations for international harmonisation of clinical pathology testing in non-clinical toxicity and safety studies are anticipated by the end of 1993. Originally presented at ECCP 93.     

Internal quality control, proficiency testing, and the clinical relevance of laboratory testing

Estimates of instrument-specific analytical performance for measurement of four chemistry analytes (calcium, cholesterol, creatinine, and glucose) were derived from 21 quality control programs that utilized the College of American Pathologists Quality Assurance Service and from 12 College of American Pathologists Comprehensive Chemistry Survey sets. The quality control-derived estimates of analytical bias were larger and level-dependent when compared with the survey results. Possible explanations for these differences include "matrix effects" due to glycol stabilization of the control materials studied and analyst bias when testing survey specimens. A number of instruments from the Quality Assurance Service pools failed to meet the allowable analytical error goals for calcium and creatinine that serve as the basis for the "fixed limits" evaluation criteria of the survey program. The methods for glucose analysis met the prescribed evaluation limits. Cholesterol analyses need significant improvement to meet the analytical requirements of long-term testing of individuals.     

Effects of pH on glucose measurements with handheld glucose meters and a portable glucose analyzer for point-of-care testing

OBJECTIVES: To determine pH effects on glucose measurements obtained with the latest generation of glucose devices, to quantitate changes in glucose measurements obtained over a wide pH range, and to assess the potential clinical risks of pH effects with use of point-of-care glucose testing. DESIGN: Paired differences of glucose measurements between pH-altered and parallel control samples with target pH 7.40 were calculated. SETTING: A pH range of 6.94 to 7.84 was used to evaluate pH effects on glucose measurements in vitro with 6 handheld glucose meters and a portable glucose analyzer at both normal, 4.81 mmol/L (86.6 mg/dL), and high, 11.16 mmol/L (201 mg/dL), glucose levels. MAIN OUTCOME MEASURES: Glucose measurements obtained from test samples and control samples were compared by calculating paired differences, which were plotted against pH to show pH effects on glucose meter measurements. RESULTS: At the normal glucose level, different pH levels did not interfere significantly with glucose measurements. At the high glucose level, a trend whereby low pH decreased and high pH increased glucose measurements was observed on the Precision G and the Precision QID glucose meters. CONCLUSION: Because of potential risk in diabetic patients with ketoacidosis and in other patients with acid-base disorders, we recommend that clinicians choose glucose devices carefully and interpret the measurements cautiously when point-of-care glucose testing is performed in critically ill patients with acidemia, alkalemia, or changing acid-base status.     

Design,fabrication and testing of a novel vascular coupling device

In this work, an innovative vascular coupling device (VCD) is created to realize quick and reliable vessel anastomosis. Vessel anastomosis is common and often necessary during trauma, replantation and free tissue transfer surgeries. The current method of vessel anastomosis is traditional hand suturing. This technique is time consuming (20–30 min), difficult, and requires complex instruments. Additionally, it requires very skilled surgeons to efficiently perform the operation. To improve the reliability and reduce the amount of time required to connect two vessels, while providing an intima-to-intima anastomosis with no foreign material in contact with the blood flow, as occurs with sutures, a series of VCDs ranging from 1.5 mm to 7 mm inner diameter are designed and fabricated from polytetrafluoroethylene (PTFE) using laser cutting. A set of installation tools are also designed and fabricated to facilitate the VCD application. A series of experiments to test the VCD functionality are performed using both latex tubes and arteries. The results showed that the anastomosis process using VCDs and the installation tools can be completed in 5 min. The coupled VCDs can withstand 20 N tensile force, which is much higher than normal physiology conditions. There is no leakage or significant effects of the VCDs on the flow. A Micro-CT scan and histology images of cadaver arteries coupled with VCDs demonstrated that the VCD keeps the vessels open and does not constrict blood flow, suggesting that the VCD could be used in more advanced testing.     

Hepatitis a virus: Virologic, clinical, and epidemiologic studies

The last decade has borne witness to accelerated expansion of our understanding of hepatitis A virus. The agent of type A hepatitis is an RNA virus with a mean diameter of 27 nm. and biochemical-biophysical properties of an enterovirus. A variety of sensitive specific serologic techniques have been developed with which to identify hepatitis A virus and antibody, and both chimpanzees and marmosets have been studied extensively as experimental animal models. As a result of these studies, in vitro cultivation of hepatitis A virus has finally been accomplished, and a commercial radioimmunoassay for IgM antibody to hepatitis A virus has been developed for the rapid diagnosis of hepatitis A virus infection during acute illness. Clinically the illness caused by hepatitis A virus is relatively mild, often subclinical, and of limited duration and does not progress to chronic liver disease. This relative clinical benignity is reflected, according to preliminary histologic observations, in the sparing of the centrozonal area of the liver lobule. Rarely, however, hepatitis A virus can cause fulminant hepatitis. Type A hepatitis is transmitted almost exclusively by the fecal-oral route, and its spread is enhanced by epidemiologic settings favoring dissemination of enteric infections. Hepatitis A virus does not contribute to transfusion associated or other types of percutaneously transmitted hepatitis. Exposure to the virus increases as a function of age and decreasing socioeconomic class, but the incidence of hepatitis A virus infection in urbanized societies is decreasing. There is no evidence for the existence of chronic hepatitis A virus carriage; natural perpetuation of hepatitis A virus in urban communities appears to depend on a reservoir of nonepidemic, clinically inapparent cases. Until a vaccine, now being developed, becomes available, prevention of hepatitis A virus infection will continue to depend on maintenance of high standards of environmental and personal hygiene and on timely administration of immune serum globulin. Such prophylaxis may confer long lasting passive-active immunity but more frequently prevents infection entirely.     

Propagation of polarized light in birefringent turbid media: a Monte Carlo study

A detailed study, based on a Monte Carlo algorithm, of polarized light propagation in birefringent turbid media is presented in this paper. Linear birefringence, which results from the fibrous structures, changes the single scattering matrix and alters the polarization states of photons propagating in biological tissues. Some Mueller matrix elements of light backscattered from birefringent anisotropic turbid media present unusual intensity patterns compared with those for nonbirefringent isotropic turbid media. This result is in good agreement with the analytic results based on the double-scattering model. Degree of polarization, Stokes parameters, and diffuse reflectance as functions of linearly birefringent parameters based on numerical results and theoretical analysis are discussed and compared in an effort to understand the essential physical processes of polarized light propagation in fibrous tissues.     

Comparative study of polarized light propagation in biologic tissues

We report the depolarization of light scattered by a variety of birefringent and nonbirefringent tissues. We used Stokes polarimetry to investigate how scatterer structures in each tissue contribute to the depolarization of linearly versus circularly polarized light propagating through that tissue. Experiments were performed on porcine blood, fat, tendon, artery, and myocardium. The results indicate that the two incident polarization states are depolarized differently depending on the structure of the sample. As seen in sphere suspensions, for tissues containing dilute Mie scatterers, circularly polarized light is maintained preferentially over linearly polarized light. For more dense tissues, however, the reverse is true. The results illustrate situations where polarized light will provide an improvement over unpolarized light imaging, information that is crucial to optimizing existing polarimetric imaging techniques.     

The HLA system: genetics, immunology, clinical testing, and clinical implications

The human major histocompatibility complex HLA is located on the short arm of chromosome 6. It is known to be the most polymorphic genetic system in humans. The biological role of the HLA class I and class II molecules is to present processed peptide antigens. The HLA system is clinically important as transplantation antigens. Molecular HLA allele typing is routinely performed to provide HLA class I and class II allele matching in unrelated donor hematopoietic stem cell transplantation. Prospective lymphocyte crossmatching is critical in solid organ transplantation to prevent allograft rejection. HLA alloimmunization causes various problems in transfusion therapy. The HLA system is associated with certain diseases, but its underlying mechanisms are not yet fully explained.