Laparoscopic photodynamic diagnosis of ovarian cancer using 5-aminolevulinic acid in a rat model

OBJECTIVE: The objective of this study was to determine the efficacy and sensitivity of laparoscopic photodynamic diagnosis to detect 5-aminolevulinic acid (ALA)-induced fluorescent tumors in an animal model. METHODS: Cancer cells were injected into the peritoneum of rats to induce peritoneal carcinomatosis. After 3-4 weeks, ALA was administered to establish fluorescence in tumor nodules. All intraperitoneal surfaces were inspected using fluorescence and white light laparoscopy. Suspicious lesions were then biopsied in vivo under either fluorescence or white light laparoscopic guidance. Fluorescence intensities of the cancerous lesions compared to normal tissues were determined. A pathologist blinded to our clinical impression analyzed all biopsied specimens. We compared the sensitivity of fluorescence and white light laparoscopic-guided detection of cancerous lesions and determined the clinical utility of fluorescent photodynamic diagnosis in detecting metastatic ovarian cancer. RESULTS: Forty-three biopsies were performed in vivo under laparoscopic fluorescent guidance and 42 biopsies were taken using white light in various regions of the peritoneal surface from nine rats. Ten biopsies were also removed from nonfluorescent regions as nontumor controls. Cancerous lesions showed significantly higher fluorescent intensity compared to noncancerous lesions. Cancerous lesions that were difficult to differentiate from normal surrounding tissue under white light conditions were clearly detected by ALA-induced fluorescence. The average size of these metastatic lesions biopsied under fluorescent light was 1.0 mm (range: 0.3-2.5) compared to 1.5 mm (range: 0.5-2.9) with white light illumination (P < 0.05). CONCLUSIONS: Fluorescent laparoscopic detection of micrometastatic ovarian cancer using ALA is significantly more sensitive than white-light laparoscopy in detecting smaller cancerous lesions in an ovarian cancer rat model. Human trials are indicated.     

Characterization, expression and complex formation of the murine Fanconi anaemia gene product Fancg

BACKGROUND: Fanconi anaemia (FA) is an autosomal recessive chromosomal instability disorder. Six distinct FA disease genes have been identified, the products of which function in an integrated pathway that is thought to support a nuclear caretaker function. Comparison of FA gene characteristics in different species may help to unravel the molecular function of the FA pathway. RESULTS: We have cloned the murine homologue of the Fanconi anaemia complementation group G gene, FANCG/XRCC9. The murine Fancg protein shows an 83% similarity to the human protein sequence, and has a predicted molecular weight of 68.5 kDa. Expression of mouse Fancg in human FA-G lymphoblasts fully corrects their cross-linker hypersensitivity. At mRNA and protein levels we detected the co-expression of Fancg and Fanca in murine tissues. In addition, mouse Fancg and Fanca proteins co-purify by immunoprecipitation. Upon transfection into Fanca-deficient mouse embryonic fibroblasts EGFP-Fancg chimeric protein was detectable in the nucleus. CONCLUSIONS: We identified a murine cDNA, Fancg, which cross-complements the cellular defect of human FA-G cells and thus represents a true homologue of human FANCG. Spleen, thymus and testis showed the highest Fancg expression levels. Although Fancg and Fanca are able to form a complex, this interaction is not required for Fancg to accumulate in the nuclear compartment.     

The multidimensional scale of independent functioning: a new instrument for measuring functional disability in psychiatric populations

The Multidimensional Scale of Independent Functioning (MSIF) is a new instrument for rating functional disability in psychiatric outpatients. The MSIF differs from other disability rating scales by providing discrete ratings of (1) role responsibility, (2) presence and level of support, and (3) performance quality. The MSIF, which consists of a semistructured interview and detailed rating anchors, was validated in 114 psychiatric outpatients. The instrument had good criterion, discriminative, interrater, and construct validity. Correlations between comparable ratings on the Social Adjustment Scale II (SAS II) ranged from 0.78 to 0.86. Nevertheless, redundancy analysis using canonical correlation demonstrated that, although the two instruments overlap, the MSIF contains information that is not contained in the SAS II. Furthermore, there was only modest shared variance with conceptually non-overlapping subscales in the SAS II. Interrater reliability (intraclass correlation coefficients) ranged from 0.74 to 1.00 for global and subscale scores. MSIF subscales performed as expected with respect to external validators such as hours of employment, earned income, supported versus nonsupported employment and housing, and mainstream versus nonmainstream educational status. MSIF global ratings were modestly correlated with IQ and psychopathology ratings, consistent with reports in the literature. Construct validity, estimated using Cronbach's alpha coefficient, was 0.72. The MSIF is a promising new instrument designed to circumvent several limitations with existing functional outcome instruments for longitudinal studies, intervention research, and services research.     

Intravitreal VEGF and bFGF produce florid retinal neovascularization and hemorrhage in the rabbit

PURPOSE: Vascular endothelial growth factor (VEGF) causes widespread retinal vascular dilation, produces breakdown of the blood-retinal barrier, and is implicated in ocular neovascularization (NV). Basic fibroblast growth factor (bFGF) also has been implicated in the production of ocular NV. This study was performed to investigate the ability of simultaneous sustained intravitreal release of both VEGF and bFGF to induce robust retinal NV in the rabbit. METHODS: Intravitreal implantation of sustained-release Hydron polymeric pellets containing both 20 microg of VEGF and 20 microg of bFGF was performed on adult male Dutch belted rabbits. In other animals either 20 microg or 50 microg bFGF-containing pellets was implanted intravitreally; also, either 20 microg VEGF or 50 microg VEGF-containing pellets was implanted. Control rabbits received either blank polymeric pellets or a pellet containing 30 microg bovine serum albumin. Eyes were examined by indirect ophthalmoscopy after surgery at 24 hrs, 48 hrs, 4 days, 7 days, 14 days, 21 days, and 28 days. Findings were documented by color fundus photography and fluorescein angiography (FA). Eyes were enucleated and prepared for histologic analysis at 28 days following intravitreal implantation of the VEGF/bFGF-containing pellets. RESULTS: In all eyes implanted with VEGF/bFGF pellets, dilation and tortuosity of existing blood vessels were observed within 48 hrs after pellet implantation. The progression of retinal vascular changes was rapid and occurred over the entire optic disk and medullary rays between 4 and 7 days. Hemorrhage occurred as early as 14 days after VEGF/bFGF pellet implantation. In eyes with massive hemorrhage, total traction retinal detachment developed after the second week. The presence of abnormal tissues at the vitreo-retinal interface within 28 days was demonstrated by light microscopy while FA showed profuse leakage of dye from anomalous vessels within the first week. Neither bFGF-exposed eyes nor control eyes showed any vascular changes. Eyes that received only VEGF-containing pellets exhibited tortuosity of existing vessels, but neither hemorrhaging nor retinal detachment occurred. CONCLUSIONS: These results demonstrate that retinal vascular changes leading to hemorrhaging is produced rapidly in the rabbit by simultaneous intravitreal release of both VEGF and bFGF. Understanding how these growth factors induce retinal NV may suggest novel therapeutic treatment strategies.     

Overexpression of Frat1 in transgenic mice leads to glomerulosclerosis and nephrotic syndrome, and provides direct evidence for the involvement of Frat1 in lymphoma progression

The proto-oncogene Frat1 was originally identified as a common site of proviral insertion in transplanted tumors of Moloney murine leukemia virus (M-MuLV)-infected Emu-Pim1 transgenic mice. Contrary to most common insertion sites implicated in mouse T cell lymphomagenesis, retroviral insertional mutagenesis of Frat1 constitutes a relatively late event in M-MuLV-induced tumor development, suggesting that proviral activation of Frat1 contributes to progression of T cell lymphomas rather than their genesis. To substantiate this notion we have generated transgenic mice that overexpress Frat1 in various organs, including lymphoid tissues. Frat1 transgenic mice develop focal glomerulosclerosis and a nephrotic syndrome, but they do not exhibit an increased incidence of spontaneous lymphomas. Conversely, these mice are highly susceptible to M-MuLV-induced lymphomagenesis, and Frat1/Pim1 bitransgenic animals develop lymphomas with increased frequency compared to Pim1 transgenic littermates. These data support a role for Frat1 in tumor progression.     

PERINATAL CAMPYLOBACTER FETUS SS JEJUNI ENTERITIS

ABSTRACT. Vesikari, T., Huttunen, L. and Mäki, R. (Department of Clinical Sciences, University of Tampere; Department of Paediatrics, Central Hospital of Päijät-Häme, and Department of Microbiology, Tampere Central Hospital, Finland). Perinatal Campylobacter fetus ss jejuni enteritis. Acta Paediatr Scand, 70:261, 1980. –A 2-day-old breast-fed male infant developed mucoid and bloody diarrhoea, and Campylobacter fetus ss jejuni was isolated from the stools but not from the blood. The probable source of transmission was his mother in whom symptoms of Campylobacter jejuni - associated illness began one day earlier. Both showed IgM, IgG and IgA antibody responses to autologous and reciprocal strains of Campylobacter jejuni as studied by ELISA.     

Subcellular Phototoxicity of Photofrin-II and Lutetium Texaphyrin in Cells In Vitro

. Three cell types including bovine pulmonary artery endothelium cells (CPAE), rat kangaroo kidney cells (PTK₂), and human larynx epidermoid carcinoma cells (Hep-2) were used to study subcellular localisation and phototoxicity of Photofrin-II and lutetium texaphyrin (Lu Tex). Cells were examined for fluorescence after administration of the photosensitisers. Subcellular regions were exposed with a laser microbeam system that used an argon ion laser pumped dye laser generating a 630 nm for Photofrin-II and 730 nm for Lu Tex. Fluorescence detection suggests that the Photofrin-II is bound primarily to the mitochondria with some diffuse fluorescence in the rest of the cytoplasm. The fluorescence in Lu Tex treated cells appears to be localised to the lysosomes. The percentage of damaged cells following light exposure to the different subcellular regions after Photofrin-II or Lu Tex treatment demonstrates that the nuclear region was the most sensitive target followed by the perinuclear region and peripheral cytoplasm region. Paper received 27 January 1998; accepted after revision 21 August 1998.     

Unimpinged and impinged anterior cruciate ligament grafts: MR signal intensity measurements

Regionalized magnetic resonance (MR) signal intensities were quantitatively measured in impinged and unimpinged anterior cruciate ligament (ACL) grafts. Images were obtained with a 1.5-T imager, and signal intensity was measured in the proximal, middle, and distal thirds of the graft. In 15 unimpinged ACL grafts, the signal intensity remained low and did not vary during the 1st year of graft implantation (45 images). In contrast, 17 impinged ACL grafts showed an increase in signal intensity in the distal two-thirds of the graft that persisted 1-3 years after implantation (P less than .001). Unimpinged grafts were placed in tibial tunnels posterior and parallel to the slope of the intercondylar roof. Reconstructions with anterior tibial tunnels resulted in graft impingement that caused increases in graft signal intensity. This increase demonstrates a clear association between surgical technique and the subsequent MR appearance of the graft.