Three-dimensional light-field microendoscopy with a GRIN lens array

Optical endoscopy has emerged as an indispensable clinical tool for modern minimally invasive surgery. Most systems primarily capture a 2D projection of the 3D surgical field. Currently available 3D endoscopes can restore stereoscopic vision directly by projecting laterally shifted views of the operating field to each eye through 3D glasses. These tools provide surgeons with informative 3D visualizations, but they do not enable quantitative volumetric rendering of tissue. Therefore, advanced tools are desired to quantify tissue tomography for high precision microsurgery or medical robotics. Light-field imaging suggests itself as a promising solution to the challenge. The approach can capture both the spatial and angular information of optical signals, permitting the computational synthesis of the 3D volume of an object. In this work, we present GRIN lens array microendoscopy (GLAM), a single-shot, full-color, and quantitative 3D microendoscopy system. GLAM contains integrated fiber optics for illumination and a GRIN lens array to capture the reflected light field. The system exhibits a 3D resolution of ∼100 µm over an imaging depth of ∼22 mm and field of view up to 1 cm². GLAM maintains a small form factor consistent with the clinically desirable design, making the system readily translatable to a clinical prototype.     

Endothelin receptor blockade during hypothermic perfusion preservation mitigates the adverse effect of preretrieval warm ischemic injury on posttransplant glomerular filtration rate

BACKGROUND: Preretrieval warm ischemic injury predisposes to both short-term and long-term dysfunction of cadaveric renal allografts. We previously reported that the excretion of the vasoactive peptide, endothelin (ET), is significantly increased during hypothermic perfusion preservation (HPP) of kidneys subjected to preretrieval warm ischemia compared with nonischemic controls. As such, the purpose of this study was to determine if endothelin receptor (ET-R) blockade during HPP would improve glomerular filtration rate (GFR) of kidneys subjected to preretrieval warm ischemia when measured in situ at 2 weeks after transplantation (Tx). METHODS: The left kidney was retrieved from 300-g Lewis rats after in situ cold perfusion and transplanted after 2 hr of HPP. A 30-min period of preretrieval warm ischemia was induced. Kidneys were divided into four groups: nonischemic controls (n=9), ischemic (isch) kidneys not receiving ET-R blockade during HPP (n=7), isch kidneys receiving the ETA receptor antagonist (n=7), and isch kidneys receiving the ETA/B receptor antagonist (n=8). ET-R blockade was induced by adding the ETA, A-147627, or the ETA/B, A-182086, receptor antagonist (Abbott Laboratories, Abbott Park, IL) directly to the preservation solution (5x10-6M). The kidneys were then isografted into genetically identical Lewis rats and GFR, determined by measurement of urinary iohexol clearance, measured 2 weeks after Tx. RESULTS: Two-week GFRs (mL/min) for each of the study cohorts are as follows: nonischemic controls, 1.18+/-0.11; ischemic (isch) only, 0.57+/-0.08 (P< or =0.05 vs. nonischemic controls); isch + ETA blockade, 0.95+/-0.15 (P< or =0.05 vs. isch only); isch + ETA/B blockade, 0.90+/-0.08 (P< or =0.05 vs. isch only). CONCLUSION: Addition of an ETA, A-147627, or an ETA/B, A-182086, receptor antagonist to preservation solution used during HPP of kidneys subjected to preretrieval warm ischemia resulted in a normalization of GFR measured 2 weeks after Tx. The data provide a basis for further investigation of the impact of ET-R blockade on both the short- and long-term adverse effects of preretrieval warm ischemic injury in cadaveric renal Tx.     

Genetic influences on secondary degeneration and wound healing following spinal cord injury in various strains of mice

Various inbred strains of mice exhibit dramatic differences in sensitivity to excitotoxic cell death induced by systemic injections of kainic acid (KA). The present study evaluates whether the same strains are also differentially sensitive to secondary degeneration after spinal cord injury, in which excitotoxic cell death is thought to play a pathogenic role. Spinal cord crush injuries were produced at T9 in two inbred strains that are resistant to KA-induced excitotoxic cell death (C57Bl/6 and Balb/c) and four strains that are sensitive (CD-1, FVB/N, 129T2 Sv/EMS, and C57Bl/10). The spinal cord was prepared for light microscopy at intervals from 1 to 56 days postinjury, and the area of damaged tissue (termed lesion size) and amount of cavitation were determined by quantitative image analysis. Lesion size increased between 1 and 7 days in all strains and then decreased steadily in a wound-healing process that occurs uniquely in mice. The extent of cavitation also gradually decreased from 7 to 56 days in all strains. Although lesion area and cavitation decreased in all strains, there were significant differences in lesion size and cavitation across strains. Specifically, lesion areas in the KA-sensitive strains FVB/N, 129T2 Sv/EMS, and CD-1 were significantly larger at 56 days postinjury than in the KA-resistant strains C57Bl/6 and Balb/c. We conclude that the genetic differences that confer resistance and sensitivity to KA-induced neurotoxicity also modify the secondary degenerative processes that occur after spinal cord injury, so that resistance to excitotoxic injury leads to smaller overall lesions and a more effective wound-healing response.     

Currarino triad: Characteristic appearances on magnetic resonance imaging and plain radiography

The Currarino triad is a complex anomaly consisting of an anorectal malformation, a sacral bone defect and a presacral mass. It was first described in 1981 and since then, approximately 250 cases have been reported. Radiology has an important part to play in the diagnosis of this entity, as the imaging features are characteristic. We report a case of Currarino triad in an infant who presented with intractable constipation and discuss relevant MRI and plain radiography findings.     

Loss of tumor-promoting activity of unleaded gasoline in N- nitrosodiethylamine-initiated ovariectomized B6C3F1 mouse liver

Unleaded gasoline (UG) vapor (2056 ppm) increased the incidence of liver tumors in a chronic bioassay and exhibited tumor-promoting activity in N-nitrosodiethylamine (DEN)-initiated female mouse liver. Estrogen inhibited mouse liver tumor development and the hepatocarcinogenic and tumor-promoting dose of UG produced uterine changes suggestive of estrogen antagonism. To directly test the hypothesis that UG-induced tumor-promoting ability is secondary to its interaction with the mouse liver tumor inhibitor, estrogen, we compared the tumor-promoting ability of UG in ovariectomized (Ovex) mice with the hepatic tumor-promoting ability of UG in intact mice. Ovaries were surgically removed at 4 weeks of age. Exposure to wholly vaporized UG (2018 ppm) under bioassay and tumor-promoting conditions began at 8 weeks of age. After 4 months of exposure, UG increased relative liver weight and hepatic microsomal cytochrome P450 pentoxyresourfin-O- dealkylase and ethoxyresorufin-O-deethylase activity to a similar extent in intact and Ovex mice. Non-focal hepatocyte proliferation, as measured by the incorporation of bromo-deoxyuridine, was not changed by UG exposure and was similar in all treatment groups. After 4 months of exposure to DEN-initiated mice, UG significantly increased the volume fraction of liver occupied by foci (three-fold) as compared to control intact mice. As expected, volume of foci was elevated in DEN/Ovex/control mice as compared to DEN/intact/control mice. In DEN/Ovex mice UG did not significantly increase the focal volume fraction. Thus, the tumor promoting activity of UG, as demonstrated by increased volume fraction of liver occupied by hepatic foci in intact mice, is greatly attenuated in Ovex mice. The volume fraction data in Ovex mice support the hypothesis that the tumor promoting activity of UG is dependent upon the interaction of UG with ovarian hormones. These data also indicate that hepatic microsomal cytochrome P450 PROD and EROD induction, hepatomegaly and non-focal hepatic LI are not specific markers of hepatic tumor promoting activity of UG.      

Prognostic indicators for breast cancer patients with one to three regional lymph node metastases, with special reference to alterations in expression levels of bcl-2, p53 and c-erbB-2 proteins

Patients with primary breast carcinoma with one to three axillary lymph node metastases but without distant metastases (n1-3) in Japan have been shown to have a 10-year disease-free survival rate of > 60%. It would be reasonable to divide n1-3 Japanese breast cancer patients into groups with high- or low-risk for recurrence and to consider post-operative adjuvant therapy. In the present study, we analyzed 228 consecutive Japanese patients with n1-3 breast cancer who underwent radical mastectomy and were followed up for a median time of 11.0 years. The expression of bcl-2, p53 and c-erbB-2 proteins in the primary tumors was examined immunohistochemically and their prognostic roles were also analyzed along with conventional clinicopathologic indicators. bcl-2 expression was correlated with positive estrogen receptor status and inversely correlated with p53, c-erbB-2 and histologic grade. Univariate analysis showed that bcl-2, p53 and c-erbB-2 expression were prognostic indicators of the patient's group as well as node status, histologic grade, tumor size, age at diagnosis, menopausal status and estrogen receptor status. Cox's regression analysis demonstrated that the number of nodes involved, menopausal status, p53 and bcl-2 were independent predictors for overall survival and that histologic grade and the number of nodes involved were independent predictors for disease-free survival. These results suggest that bcl-2 expression in combination with p53 and c-erbB-2 expression, the number of lymph node metastases, histologic grade and menopausal status are useful in selecting subgroups of n1-3 breast cancer patients with good or poor prognoses.      

Risk factors for deaths in under-age-five children attending a diarrhoea treatment centre

Few case-control studies have examined possible risk factors for diarrhoeal deaths in under-age-five children in the developing countries. We analysed data from the surveillance system of our diarrhoea treatment centre/hospital for the period 1990-94 on 928 children less than 5 years of age. In univariate analysis, 11 factors were significantly associated with death: lack of breastfeeding, severe malnutrition, complicated diarrhoea, pneumonia, xerophthalmia, duration of diarrhoea 7-14 days, moderate or severe dehydration, recent history of measles, Shigella flexneri infection, maternal illiteracy, and very low household income. Rotavirus diarrhoea was negatively associated with fatal outcome. In the assessment of severe malnutrition, weight-for-height measurement discriminated mortality risk better than weight-for-age or height-for-age indices. Only two factors retained their significance, severe malnutrition and non-breastfeeding in the multivariate analysis with adjusted odds ratio (95% confidence interval) of 84.2 (9.1, 775.9) and 4.2 (1.3, 13.2) respectively.     

Short stay facilities: the future of efficient paediatric emergency services

OBJECTIVE: To assess the reactions of parents and their children to the request for a blood sample and an attempt to take blood. METHODS: 1859 children aged 1.5-4.5 years took part in a national survey of diet and nutrition. A retrospective inquiry of the parents' and children's reported reactions was carried out six to 18 months later by postal questionnaire sent only to the 1157 who had given consent for an attempt to take blood. RESULTS: 866 questionnaires were returned; 790 were from parents of children in whom an attempt to take blood had been successful. Thirteen per cent said that their child had given blood previously. About 30% discussed the request with the family doctor or nurse. Some 90% said that they were given enough information and that the phlebotomist was sympathetic. Attempting to take blood caused upset in over 50%, which, in most, lasted for less than five minutes. A substantial minority were upset for up to 30 minutes and a few much longer. Bruising or bleeding occurred in 20-27%. Degree and duration of upset were both adversely associated with a failed attempt to obtain blood. CONCLUSION: The majority of preschool children experienced no more than a little upset of short duration after an attempt to take blood, but a substantial minority exhibited a greater degree of upset. These responses should be taken into account when assessing the benefits and risks of the procedure. The best equipment and expertise should be employed for taking blood as successful attempts are less upsetting.     

Nutritional factors and thalassaemia major

Abnormal growth is a common feature of thalassaemia major in children. In an attempt to determine whether it has a nutritional cause, 12 children aged 1 to 3 years with thalassaemia major were studied under metabolic ward conditions. Nutritional status was assessed by anthropometry and biochemistry before and after an intensive nutrition regimen. Five children had wasting or stunting on admission. As a result of the nutrition intervention, mean weight for height improved significantly. The mean height increase of 0.4 cm after one month was not significant. Plasma zinc, depressed in half the children on admission, improved, as did alpha tocopherol, while copper decreased. Plasma insulin-like growth factor-I also increased commensurate with improved growth. Fat absorption was normal in all children. Undernutrition is an important cause of associated growth disturbances in children with thalassaemia major. Malnutrition was primarily caused by inadequate nutrient intake, as indicated by the capacity to gain weight appropriately when provided with nutrition support, and by the absence of intestinal malabsorption. While long term studies are required to determine if nutritional support will prevent stunting, these results underscore its central role in preventing nutritional deficiencies and in promoting normal growth in thalassaemic children.