Ocular sequelae in extremely premature infants at 5 years of age

Objective To report long-term ophthalmological sequelae in extremely premature infants at 5 years and to determine the relationship between neonatal variables (including retinopathy of prematurity; ROP) and the 5 year ophthalmological outcome of these infants.
Methodology The study cohort comprised 84 surviving infants born with a birthweight <1000 g or gestational age <28 weeks from June 1985 to December 1989. All infants had an ophthalmological assessment between 34 and 40 weeks post conceptional age to document grade of ROP and were assessed at 5 years of age for fundoscopy, visual acuity, refractive error and ocular mobility.
Results Of the 84 long-term survivors 69 (82%) were formally assessed at 5 years. Overall, 30 (43%) had some form of ocular disorder. Nineteen (27%) had reduced visual acuity of <6/6 and three of these were blind. Myopia > −0.5 dioptre was noted in eight (12%), hypermetropia ≥2.0 dioptre in five (8%), astigmatism in seven (11%) and strabismus was present in nine (14%) of the cohort. There was a significant relationship ( P <0.0001) between the incidence of ocular disorders and ROP. However, even those premature children without ROP had a 31% incidence of ocular disorder at 5 years.
Conclusion Long-term ophthalmological follow-up is recommended in all extremely premature infants regardless of the presence of ROP in the neonatal period.     

Computed tomography in miliary tuberculosis: Comparison with plain films,bronchoalveolar lavage,pulmonary functions and gas exchange

Computed tomography (CT) of the chest, pulmonary function tests, bronchoalveolar lavage (BAL) and arterial blood gas analysis were performed in 26 patients with non-HIV miliary tuberculosis (MTB). CT was repeated after treatment in 11 patients. Nodular lesions were characteristically seen on CT. CT showed discrete and fine nodules in five patients in whom the lesions appeared to be larger than miliary on chest X-rays. Coalescing nodular lesions were noted on chest X-rays (n= 7) and CT (n= 18). Consolidation (n= 6), cavitation (n= 4), fibrosis (n= 9) and air trapping (n= 14) were detected on CT only. During follow up, air trapping increased h = 14) and in some patients it appeared for the first time (n= 2). Lymph node enlargement and calcification were seen on both chest X-rays (n= 9 and (n= 3, respectively) and CT (n= 12 and n= 7, respectively). Pleural involvement was also seen in chest X-rays (n= 4) and CT (n= 5). Total lung capacity was higher in patients with a chest X-ray score > 10. Similarly a higher total cell count in BAL fluid was observed in patients with a CT score > 10. It is concluded from this study that CT is superior to chest X-rays in detecting nodular lesions, lymphadenopathy and air trapping in patients with MTB.     

In-situ competition between protamine and fluorochromes for sperm DNA

In this study we investigated the relationship between the presence of bound protamine on mouse and human sperm DNA and the level of chromomycin A3 (CMA3) and 4'6-diamidino-2-phenylindole (DAPI) fluorescence. This was accomplished by performing a competition assay between salmon protamine and fluorochromes on decondensed spermatozoa that had their nuclear proteins extracted and were fixed on slides. Various concentrations (0, 0.005, 0.0225, 0.05, 0.225, 0.5 and 5 mg/ml) of salmon protamine were added to either the CMA3 or DAPI staining solutions. Fluorescence emission measurements of stained sperm nuclei were then performed using a microfluorometer. When the treated decondensed sperm heads were stained with either CMA3 or DAPI all spermatozoa were found to fluoresce intensely. The addition of protamines to the spermatozoa led to an elimination of CMA3 fluorescence, while the intensity of DAPI staining was decreased to approximately 50% at the highest concentrations of protamine. The addition of increasing amounts of salmon protamine also induced the sperm nuclei to regain their initial condensed appearance. This study shows that protamine retains a strong affinity for sperm DNA in situ and that CMA3 fluorescence is a strong indicator of the protamination state of spermatozoa.      

Diet, caloric restriction, and the rodent bioassay

The diet can significantly alter the results of toxicity and carcinogenicity studies. Ad libitum (AL) overfeeding of excessive calories to sedentary adult rodents is one of the most poorly controlled variables affecting the current rodent bioassay. AL-overfed rodents develop an early onset of adverse metabolic events, endocrine- disruptive degenerative diseases, and tumors that result in early morbidity and mortality. AL food consumption is extremely variable, but has a strong correlation with adult body weight, obesity, and survival. AL feeding of diets with modified protein, fiber, and energy content are not as effective as simple, moderate dietary (caloric) restriction (DR) in controlling these study variables. Moderate DR (70-75% of adult AL) is operationally simple and controls adult body weights, prevents obesity, and improves health and survival by reducing or delaying diet- related endocrine, renal, and cardiac diseases. Moderate DR provides a uniform rodent model, increases treatment exposure time, and increases the statistical sensitivity of these chronic bioassays to detect true treatment effects. Feeding a balanced diet by a moderate DR regimen of 70-75% of the maximum, unrestricted adult AL food intake is recommended for conducting well-controlled toxicity and carcinogenicity studies.      

Uterine leiomyomas: correlation of MR, histopathologic findings, and symptoms

Magnetic resonance (MR) imaging, symptoms, and pathologic findings were correlated in 59 uterine leiomyomas from 23 patients. The tumors varied from less than 1 cm to 18 cm in diameter. Fifty-seven leiomyomas were identified in the corpus uterus, one was located within the broad ligament, and another was detected in the cervix. Among the corpus lesions, 9 were correctly identified on MR images as subserosal and 37 as intramural. Of 11 tumors assigned at surgery to the submucosal group, 10 had been accurately defined with MR. On MR, myomas associated with hypermenorrhea produced an anatomic disruption of the "junctional zone" (the low-intensity band seen at the myometrium-endometrium junction on T2 contrast images). Long TR (2 sec) and TE (56 msec) parameters (T2 contrast images) yielded the best contrast resolution between leiomyoma and surrounding myometrium. Correlation of MR with histologic features demonstrated 2 groups of lesions. Leiomyomas free of degenerative changes emitted homogeneous signals of low intensity. Contrast between tumor and myometrium was -16% on the T1 contrast image and increased to -44 +/- 16% on the T2 contrast image. Leiomyomas with hyaline, myxomatous, or fatty degeneration demonstrated various degrees of inhomogeneity, best seen on images obtained with long TR and TE. It is concluded that MR is an accurate modality for imaging uterine leiomyomas, since it clearly demonstrates tumor number, size, location, and the presence and extent of degeneration.     

Di-Peptide-Modified Gemini Surfactants as Gene Delivery Vectors: Exploring the Role of the Alkyl Tail in Their Physicochemical Behavior and Biological Activity

The aim of this work was to elucidate the structure-activity relationship of new peptide-modified gemini surfactant-based carriers. Glycyl-lysine modified gemini surfactants that differ in the length and degree of unsaturation of their alkyl tail were used to engineer DNA nano-assemblies. To probe the optimal nitrogen to phosphate (N/P) ratio in the presence of helper lipid, in vitro gene expression and cell toxicity measurements were carried out. Characterization of the nano-assemblies was accomplished by measuring the particle size and surface charge. Morphological characteristics and lipid organization were studied by small angle X-ray scattering technique. Lipid monolayers were studied using a Langmuir-Blodgett trough. The highest activity of glycyl-lysine modified gemini surfactants was observed with the 16-carbon tail compound at 2.5 N/P ratio, showing a 5- to 10-fold increase in the level of reporter protein compared to the 12 and 18:1 carbon tail compounds. This ratio is significantly lower compared to the previously studied gemini surfactants with alkyl or amino- spacers. In addition, the 16-carbon tail compound exhibited the highest cell viability (85%). This high efficiency is attributed to the lowest critical micelle concentration of the 16-tail gemini surfactant and a balanced packing of the nanoparticles by mixing a saturated and unsaturated lipid together. At the optimal N/P ratio, all nanoparticles exhibited an inverted hexagonal lipid assembly. The results show that the length and nature of the tail of the gemini surfactants play an important role in determining the transgene efficiency of the delivery system. We demonstrated here that the interplay between the headgroup and the nature of tail is specific to each series, thus in the process of rational design, the contribution of the latter should be assessed in the appropriate context.     

Overexpression of RGC-32 in colon cancer and other tumors

Tumors often exhibit deregulation of the cell cycle and overexpression of cyclins and cyclin-dependent kinases (CDKs). Response gene to complement (RGC)-32 is a substrate and regulator of CDC2 and its overexpression induces cell cycle activation. We investigated RGC-32 mRNA and protein expression in tumors with special emphasis in colon carcinoma. By using an expression array technique we found that 19% of tumor tissues showed increased RGC-32 mRNA expression over the levels of corresponding normal tissues. On the other hand, an increased RGC-32 protein was found in 70% of colon adenocarcinoma samples tested. In colon carcinomas, two major patterns of RGC-32 immunoreactivity were seen: staining of malignant epithelial cells only in some tumors and RGC-32 reactivity of both malignant epithelia as well as cells in the interstitium in others. Colonic epithelium obtained from normal individuals was consistently negative for RGC-32 protein. Overexpression of RGC-32 protein was found in other tumors including prostate, bladder, breast, lung, and other digestive tract tumors. RGC-32 expression was present in the same malignant epithelial cells that also expressed the proliferation marker Ki-67. Our data suggest that RGC-32 overexpression might be part of the deregulation of the cell cycle that is required for the growth of tumor cells.     

Tumor imaging in small animals with a combined micro‐CT/micro‐DSA system using iodinated conventional and blood pool contrast agents

X‐ray based micro‐computed tomography (CT) and micro‐digital subtraction angiography (DSA) are important non‐invasive imaging modalities for following tumorogenesis in small animals. To exploit these imaging capabilities further, the two modalities were combined into a single system to provide both morphological and functional data from the same tumor in a single imaging session. The system is described and examples are given of imaging implanted fibrosarcoma tumors in rats using two types of contrast media: (a) a new generation of blood pool contrast agent containing iodine with a concentration of 130 mg/mL (Fenestra? VC, Alerion Biomedical, San Diego, CA, USA) for micro‐CT and (b) a conventional iodinated contrast agent (Isovue®‐370 mg/mL iodine, trademark of Bracco Diagnostics, Princeton, NJ, USA) for micro‐DSA. With the blood pool contrast agent, the 3D vascular architecture is revealed in exquisite detail at 100 µm resolution. Micro‐DSA images, in perfect registration with the 3D micro‐CT datasets, provide complementary functional information such as mean transit times and relative blood flow through the tumor. This imaging approach could be used to understand tumor angiogenesis better and be the basis for evaluating anti‐angiogenic therapies. Copyright © 2006 John Wiley & Sons Ltd.