Leptomeninges as a site of relapse in locally controlled,diffuse pontine glioma with review of literature

Case report Leptomeningeal involvement in diffuse intrinsic brain stem gliomas is rarely diagnosed clinically and in majority of the instances diagnosed only on postmortem examination. We report two cases of diffuse pontine glioma diagnosed clinicoradiologically and treated with conventional radiotherapy.Observations On follow-up, both patients showed clinical features suggestive of meningeal spread although imaging for pontine tumor showed stable disease. Leptomeningeal disease in the spine was confirmed on imaging and in one case by cerebrospinal fluid examination also. During the follow-up of patients with pontine glioma, the possibility of leptomeningeal involvement must be borne in mind.     

Serial circulating vasopressin levels in children with septic shock.

BACKGROUND: Septic shock is an important cause of death in pediatric intensive care units. Initial evaluations have shown that vasopressin may have a role in catecholamine refractory shock in adults. It is important to determine whether children with septic shock have deficiency of vasopressin. This will help in defining the role of vasopressin in septic shock. DESIGN: Prospective cohort study. SETTING: Pediatric intensive care unit of a tertiary care hospital in north India. PATIENTS: Patients were children with septic shock, and controls were children with sepsis but no shock. STUDY DESIGN: Vasopressin levels in plasma were determined by enzyme-linked immunosorbent assay for children with septic shock at diagnosis (baseline) and thereafter at 24, 48, and 96 hrs to determine the time trends. The baseline vasopressin values for children with septic shock were compared with those for children without shock. RESULTS: The median (95% confidence interval) vasopressin level at baseline in children with septic shock was 116 (63.3-130.7) pg/mL, and in children with sepsis but no shock it was 106 (61.7-131.77) pg/mL. The median value for survivors was 76 (44.6-130.9) pg/mL, and for nonsurvivors, 118 (81.7-259) pg/mL (p = .16). The serial values also did not show any significant changes; the values at 24 hrs (n = 17), 48 hrs (n = 16), and 96 hrs (n = 15) were 105 (76.1-125.9), 105 (41.4-155.5), and 109.5 (54.9-154.8) pg/mL, respectively. CONCLUSIONS: The results of our study suggest that vasopressin levels are elevated in children with septic shock and that serial values up to 96 hrs do not show any decline.     

Ultrasound biomicroscopic features of spherophakia

Background: Spherophakia is an uncommon diagnosis. This is the first case report of spherophakia evaluated by ultrasound biomicroscopy.
Methods: Ultrasound biomicroscopy is a new diagnostic technique developed by one of the authors and provides images with microscopic resolution of the anterior segment. A patient with spherophakia was evaluated by ultrasound biomicroscopy (Zeiss-Humphrey, 50MHz) before and after YAG laser iridotomy.
Results: Ultrasound biomicroscopic assessment revealed a shallow anterior chamber, a very steep anterior lens curvature, iridolenticular contact, elongated zonules, and an increased distance between the lens equator and the ciliary processes. Angle closure glaucoma was due to a pupil block mechanism. The pupil block was relieved by YAG laser iridotomy.
Conclusions: Ultrasound biomicroscopy is a useful technique to confirm the diagnosis of spherophakia. The pupil block in spherophakia is relieved by YAG laser iridotomy.     

Geometric Resistance and Microvascular Network Architecture of Human Colorectal Carcinoma

Objective : To measure the geometric resistance to blood flow in human colorectal carcinoma. Although tumor blood flow is of central importance in both the detection and the treatment of cancer, the determinants of blood flow through the neoplastic circulation are poorly understood. Methods : Human colorectal carcinomas (tissue weight = 272 g ± 43 g (SD), n = 6) were perfused ex vivo with a buffered physiological salt solution of known viscosity at flow rates ranging from 2.5 to 40 ml/min and perfusion pressures from 8 to 100 mm Hg. The geometric resistance was determined from the slope of the pressure-flow curve. For examination of the principal determinant of geometric resistance, the vascular architecture, one of the tumors was perfused with Batson's No. 17 polymer and macerated in KOH to produce a positive vascular cast that was used for measurement of vascular branching patterns and dimensions. Results : The pressure-flow relationship was linear at perfusion pressures above 40 mm Hg, and the geometric resistance, z₀, was constant at approximately 6.5 ± 10⁹g/cm³. Below 40 mm Hg, z₀ increased rapidly. The architecture of the arteriolar and capillary networks of human colorectal carcinoma is similar to those of experimental rodent tumors. Capillaries in planar and nonplanar mesh-works had mean segment diameters of 11 ± 2 and 9.6 ± 2 μm, lengths of 46 ± 24 and 107 ± 40 μm, and intercapillary distances of 46 ± 13 and 74 ± 24 μm, respectively. Conclusions : The geometric flow resistance in neoplastic tissue is 1–2 orders of magnitude higher than that observed in normal tissues. A decrease in functional vascular cross-sectional area may explain the additional increase in resistance at small perfusion pressures. The observed flow resistance may be due to the specialized arteriolar and capillary network architecture, pressures exerted by proliferating cancer cells, and/or coupling between vascular and extravascular flow. These observations demonstrate that tumor vascularity alone may not be indicative of flow resistance or tumor susceptibility to blood-borne therapeutic agents.     

Identification of amino acid residues of anthrax protective antigen involved in binding with lethal factor

Protective antigen (PA) and lethal factor (LF) are the two components of anthrax lethal toxin. PA is responsible for the translocation of LF to the cytosol. The binding of LF to cell surface receptor-bound PA is a prerequisite for the formation of lethal toxin. It has been hypothesized that hydrophobic residues P184, L187, F202, L203, P205, I207, I210, W226, and F236 of domain 1b of PA play an important role in the binding of PA to LF. These residues are normally buried in the 83-kDA version of PA, PA83, as determined by the crystal structure of PA. However, they become exposed due to the conformational change brought about by the cleavage of PA83 to PA63 by a cell surface protease. Mutation of the above-mentioned residues to alanine resulted in mutant proteins that were able to bind to the cell surface receptors and also to be specifically cleaved by the cellular proteases. All the mutant proteins except the F202A, L203A, P205A, and I207A mutants were able to bind to LF and were also toxic to macrophage cells in combination with LF. It was concluded that residues 202, 203, 205, and 207 of PA are essential for the binding of LF to PA.     

Relationship between oxidative stress and embryotoxicity of hydrosalpingeal fluid

BACKGROUND: Oxidative stress mechanisms are involved in the pathophysiology of many reproductive disorders. The objective of this study was to characterize oxidative stress parameters in hydrosalpingeal fluid (HSF) and examine their possible role in early embryo development. METHODS AND RESULTS: HSF was aspirated at laparoscopic salpingectomy in 11 infertile women. Reactive oxygen species (ROS), total (non-enzymatic) antioxidant capacity (TAC) and lipid peroxidation (LPO) were assayed. Two-cell mouse embryos were incubated with 25, 50 or 75% HSF and the blastocyst development rate was observed. ROS was detected in five of 11 (45%) HSF samples with a mean of 4.2 x 10(4) c.p.m. LPO was detected in all samples at a mean (+/- SD) value of 5575.4 +/- 6091.9 micromol/l malonaldehyde. The mean blastocyst development rate at 25, 5+/- 0 and 75% HSF and in the control group was 88.9 +/- 9.4, 65.7 +/- 19.1, 45.7 +/- 5.7 and 96.7% respectively (P < 0.0001). The blastocyst development rate was positively correlated to ROS concentrations (P < 0.02) but was not significantly related to LPO. CONCLUSIONS: The blastocyst development rate decreased with increasing concentrations of HSF. For the first time, the presence of ROS, LPO and TAC activity in human HSF was characterized. A possible role of oxidative stress in the embryotoxicity of HSF is suggested.     

Relationship between ROS production, apoptosis and DNA denaturation in spermatozoa from patients examined for infertility

BACKGROUND: The aim of this study was to examine the role of apoptosis and reactive oxygen species (ROS) in inducing DNA damage in ejaculated spermatozoa. METHODS: We examined ejaculated spermatozoa from 31 patients examined for infertility and 19 healthy donors for apoptosis, production of ROS and DNA damage using annexin V binding, chemiluminescence assay and sperm chromatin structure assay. RESULTS: The percentage of spermatozoa that underwent apoptosis in the whole ejaculate and mature fraction was higher in the patients than in the donors (P<0.001 and P=0.009, respectively). Levels of ROS in the whole ejaculate and immature fraction were higher in the patients than in the donors (P=0.002 and P=0.009). Apoptosis was significantly correlated with ROS within patients in the whole ejaculate [r (95% confidence interval)=0.53 (0.19-0.86)] and in the mature [0.71 (0.39-1.00)] and immature spermatozoa [0.75 (0.45-1.00)]. Only apoptosis and the DNA fragmentation index (DFI) were significantly correlated within patients in the whole ejaculate [0.57 (0.18-0.97)]. CONCLUSIONS: DNA damage may be induced by oxidative assault. Apoptosis may not contribute significantly to the DNA damage.     

Fine-needle aspiration cytology of malignant peripheral nerve sheath tumors

The histopathologic features of malignant peripheral nerve sheath tumors (MPNSTs) have been well described. There have been limited studies on the cytologic features of MPNST. In this present study, we have retrospectively reviewed eight histopathology confirmed cases of MPNST over a 5-year period. Detailed cytomorphological analysis of these cases was carried out individually by two observers. On cytology, these cases were diagnosed as benign spindle-cell tumor (two), spindle-cell tumor possibly benign (one), spindle-cell tumor possibly malignant (one), malignant spindle-cell tumor (two), spindle-cell tumor, and neural origin (two). The cardinal cytomorphologic features were loosely cohesive clusters and fascicular arrangement of spindle cells with rounded ends. The kinking of nuclei was not a conspicuous finding. Fibrillary background was noted in two of the cases. Nuclear pleomorphism was ranged from mild to moderate degree. One case exhibited extensive intranuclear pseudoinclusions. Mitotic figures (including atypical forms) were present in almost all the cases. Possibly a constellation of cytologic features such as clusters of short and long fascicles of cells admixed with dissociated spindle cells of round-ended nuclei and prominent nucleoli on myxoid or fibrillary background and frequent mitosis may be helpful in diagnosis of MPNSTs. The cytomorphologic features along with clinical correlation are necessary to increase the diagnostic accuracy of MPNST on aspiration cytology.