Minilaparotomy staging pelvic lymphadenectomy follow-up: a safe alternative to standard and laparoscopic pelvic lymphadenectomy

Granulocyte transfusion therapy has been used infrequently in the last 10 to 15 years, in large part because its efficacy in the treatment of infected neutropenic patients has not been impressive. This perceived lack of efficacy has been attributed primarily to the fact that the dose of granulocytes obtainable with standard leukapheresis techniques has been inadequate. With the availability of recombinant granulocyte colony-stimulating factor (G-CSF) to stimulate neutrophilia in normal donors and increase the number of granulocytes that can be collected, there is now renewed interest in this form of transfusion therapy. Recent studies have shown that stimulation with G-CSF, with or without corticosteroids, is well tolerated by normal donors and that granulocyte yields are increased three- to four-fold. Blood neutrophil counts in patients receiving these large cell doses rise substantially, often to normal or near normal levels, and commonly remain elevated for 24 hours or more. In vitro and in vivo measurements have shown that the functional capabilities of granulocytes collected from G-CSF stimulated donors appear to be normal. Although early reports have been encouraging, the clinical efficacy of this new level of granulocyte transfusion therapy has been yet to be determined.     

Vascular endothelial growth factor (VEGF)-C synergizes with basic fibroblast growth factor and VEGF in the induction of angiogenesis in vitro and alters endothelial cell extracellular proteolytic activity

Vascular endothelial growth factor-C (VEGF-C) is a recently characterized member of the VEGF family of angiogenic polypeptides. We demonstrate here that VEGF-C is angiogenic in vitro when added to bovine aortic or lymphatic endothelial (BAE and BLE) cells but has little or no effect on bovine microvascular endothelial (BME) cells. As reported previously for VEGF, VEGF-C and basic fibroblast growth factor (bFGF) induced a synergistic in vitro angiogenic response in all three cells lines. Unexpectedly, VEGF and VEGF-C also synergized in the in vitro angiogenic response when assessed on BAE cells. Characterization of VEGF receptor (VEGFR) expression revealed that BME, BAE, and BLE cell lines express VEGFR-1 and -2, whereas of the three cell lines assessed, only BAE cells express VEGFR-3. We also demonstrate that VEGF-C increases plasminogen activator (PA) activity in the three bovine endothelial cell lines and that this is accompanied by a concomitant increase in PA inhibitor-1. Addition of alpha2-antiplasmin to BME cells co-treated with bFGF and VEGF-C partially inhibited collagen gel invasion. These results demonstrate, first, that by acting in concert with bFGF or VEGF, VEGF-C has a potent synergistic effect on the induction of angiogenesis in vitro and, second, that like VEGF and bFGF, VEGF-C is capable of altering endothelial cell extracellular proteolytic activity. These observations also highlight the notion of context, i.e., that the activity of an angiogenesis-regulating cytokine depends on the presence and concentration of other cytokines in the pericellular environment of the responding endothelial cell.     

Case report: an unusual presentation of gout

The efficacy of ear canal flushing and ear canal and mouth swabbing methods for the isolation of mycoplasmas was investigated in 39 goats. Of the 19 goats positive for Mycoplasma spp., 14 (73.7%) were positive with the ear canal flushing method, 4 (21.0%) were positive with both ear canal flushing and mouth swabbing methods, and 1 (5.3%) was positive by the mouth swabbing method. Mycoplasma arginini, M. mycoides subsp. mycoides, and M. mycoides subsp. capri were identified by direct immunofluorescence and growth inhibition tests. Previous reports on the isolation of M. arginini from the ear canal of goats were not found in the literature.     

Children experiencing violence. I: Parental use of corporal punishment

OBJECTIVE: This study was undertaken to reveal the prevalence of corporal punishment in Alexandria and its' correlates with family background and child's behavior and characteristics. METHODS: A cross sectional survey targeting preparatory and secondary school children was conducted. The multistage random sample technique was adopted to select a representative sample of this population. Subjects were requested to complete a self-administered questionnaire to collect relevant information. Data were analyzed using the univariate and multivariate analyses. RESULTS: This study revealed that more than one-third (37.47%) of children were disciplined physically in the form of beating and a few were also burned or tied. In 25.83% of them, this harsh discipline led to physical injuries of variable degrees of severity amounting to fractures, loss of consciousness, and permanent disability. Predictive family background for the use of corporal punishment were: living in an apartment shared with strangers; high crowding index; constant fights and quarrels between family members; lack of regular relation with relatives and acquaintance as well as an income insufficient to meet the family basic needs. Predictive child's characteristics and behavior included young age; disobedience; telling lies; destroying others' belongings; acting disrespectfully to parents; communicating poorly with their parents; running away from home; and poor school achievement, in addition to other determinants. CONCLUSION: A proportion of children are subjected to extreme physical brutality amounting to abuse in a disciplinary context. Parents' education and the establishment of effective parent-child communication are deemed essential to combat this phenomenon.     

Calcium-dependent and -independent interfacial binding and catalysis of cytosolic group IV phospholipase A2

Cytosolic group IV phospholipase A2 (cPLA2) plays a role in liberating arachidonic acid from the sn-2 position of mammalian cellular phospholipids. The enzyme consists of a catalytic domain joined to an N-terminal calcium-dependent, membrane binding domain (C2 domain). The interfacial binding properties of the full-length, nonphosphorylated enzyme and its C2 domain to phospholipid vesicles were studied as a function of vesicle phospholipid composition and calcium concentration. The binding of cPLA2 to phosphatidylcholine vesicles is mostly governed by its C2 domain; binding is relatively weak, and calcium enhances binding and interfacial catalysis by about 10-fold. Catalytically productive interfacial binding was measured by monitoring the increase in the rate of cPLA2-catalyzed hydrolysis of a fluorimetric substrate present in vesicles as a function of bulk vesicle concentration. Enzyme-vesicle binding was also measured by fluorescence as was enzyme-calcium binding. Compared to zwitterionic vesicles, cPLA2 binding to anionic phosphatidylmethanol vesicles is of higher affinity and calcium-independent, although calcium is required for the binding of the C2 domain to these anionic vesicles. cPLA2 is fully catalytically active on phosphatidylmethanol vesicles in the absence of calcium. Phosphatidylserine is not a good replacement for phosphatidylmethanol for inducing high-affinity, calcium-independent binding of cPLA2. These results reveal two modes of catalytically productive interfacial binding of cPLA2: calcium-dependent anchoring via the C2 domain and a calcium-independent component involving a phosphatidylmethanol recognition element in the catalytic domain. They also show that membrane binding of cPLA2 is not, in general, predicted by the interfacial binding properties of its C2 domain.     

Blockade of the voltage-gated potassium channel Kv1.3 inhibits immune responses in vivo

The voltage activated K+ channel (Kv1.3) has recently been identified as the molecule that sets the resting membrane potential of peripheral human T lymphoid cells. In vitro studies indicate that blockage of Kv1.3 inhibits T cell activation, suggesting that Kv1.3 may be a target for immunosuppression. However, despite the in vitro evidence, there has been no in vivo demonstration that blockade of Kv1.3 will attenuate an immune response. The difficulty is due to species differences, as the channel does not set the membrane potential in rodent peripheral T cells. In this study, we show that the channel is present on peripheral T cells of miniswine. Using the peptidyl Kv1.3 inhibitor, margatoxin, we demonstrate that Kv1.3 also regulates the resting membrane potential, and that blockade of Kv1.3 inhibits, in vivo, both a delayed-type hypersensitivity reaction and an Ab response to an allogeneic challenge. In addition, prolonged Kv1.3 blockade causes reduced thymic cellularity and inhibits the thymic development of T cell subsets. These results provide in vivo evidence that Kv1.3 is a novel target for immunomodulation.     

Administration of ATP-MgCl2 following hemorrhage and resuscitation increases hepatic phosphoenolpyruvate carboxykinase and decreases pyruvate kinase activities

Since administration of ATP-MgCl2 following trauma and hemorrhagic shock improves tissue perfusion as well as cell and organ function, the aim of this study was to determine whether this agent has any salutary effects on the hepatic rate-controlling enzymes specific for gluconeogenesis, such as phosphoenolpyruvate carboxykinase (PEPCK), and for glycolysis, such as pyruvate kinase (PK), under such conditions. To study this, rats underwent a 5-cm midline laparotomy (i.e., trauma-induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of maximum bleed out volume was returned in the form of Ringer's lactate (RL). The animals were then resuscitated with 3 times the volume of shed blood with RL over 45 min, followed by 2 times RL with ATP-MgCl2 (50 micromol/kg body wt.) or an equivalent volume of normal saline over 95 min. Hepatic PEPCK, PK and glucokinase activities were determined 4 h after the completion of resuscitation. The mRNA levels of PEPCK and PK in the isolated hepatocytes were determined by Northern blot analysis. The results indicate that glucokinase activity was not significantly altered after hemorrhage, irrespective of ATP-MgCl2 treatment. Although the mRNA levels of PEPCK were similar in all groups, PEPCK activity decreased significantly after hemorrhage. ATP-MgCl2 treatment, however, restored PEPCK activity. Hemorrhage resulted in an increase in PK activity and its mRNA. ATP-MgCl2 treatment significantly decreased PK activity and the mRNA. Thus, up-regulation of the gluconeogenic enzyme, PEPCK, and down-regulation of the glycolytic enzyme, PK, by ATP-MgCl2 may be responsible, in part, for the beneficial effects of this agent following trauma-hemorrhage and resuscitation.     

Effect of source of iron on duodenal absorption of iron, calcium, phosphorous, magnesium, copper and zinc in rats with ferropoenic anaemia

The purpose of this study was to undertake a critical review of the potential role of magnetic resonance imaging (MRI) in the evaluation of low back pain (LBP) and to determine if there were differences in the MRI appearances between various occupational groups. The study group, 149 working men (78 aged 20-30 years and 71 aged 31-58 years) from five different occupations (car production workers, ambulance men, office staff, hospital porters and brewery draymen), underwent MRI of the lumbar spine. Thirty-four percent of the subjects had never experienced LBP. Twelve months later, the examination was repeated on 89 men. Age-related differences were seen in the MRI appearances of the lumbar spine. Disc degeneration was most common at L5/S1 and was significantly more prevalent (P < 0.01) in the older age group (52%) than in the younger age group (27%). Although LBP was more prevalent in the older subjects there was no relationship between LBP and disc degeneration. No differences in the MRI appearance of the lumbar spine were observed between the five occupational groups. Overall, 45% had 'abnormal' lumbar spines (evidence of disc degeneration, disc bulging or protrusion, facet hypertrophy, or nerve root compression). There was not a clear relationship between the MRI appearance of the lumbar spine and LBP. Thirty-two percent of asymptomatic subjects had 'abnormal' lumbar spines and 47% of all the subjects who had experienced LBP had 'normal' lumbar spines. During the 12-month follow-up period, 13 subjects experienced LBP for the first time. However, there was no change in the MRI appearances of their lumbar spines that could account for the onset of LBP. Although MRI is an excellent technique for evaluating the lumbar spine, this study shows that it does not provide a suitable pre-employment screening technique capable of identifying those at risk of LBP.     

Tumor-associated hyaluronic acid: a new sensitive and specific urine marker for bladder cancer

Hyaluronic acid (HA), a glycosaminoglycan, is known to promote tumor cell adhesion and migration, and its small fragments stimulate angiogenesis. We compared levels of HA in the urine of normal individuals and patients with bladder cancer or other genitourinary conditions, using a sensitive ELISA-like assay. Among the 144 specimens analyzed, the urinary HA levels of bladder cancer patients with G1 (255 +/- 41.7 ng/mg), G2 (291.8 +/- 68.3 ng/mg) and G3 (428.4 +/- 67 ng/mg) tumors are 4-9-fold elevated as compared to those of normal individuals (44.7 +/- 6.2 ng/mg) and patients with other genitourinary conditions (69.5 +/- 6.8 ng/mg; P < 0.001). Urinary HA measurement by the ELISA-like assay shows a sensitivity of 91.9% and specificity of 92.8% to detect bladder cancer. Thus, urinary HA measurement is a simple, noninvasive yet highly sensitive and specific method for bladder cancer detection. The increase in urinary HA concentration is a direct correlate of the elevated tumor-associated HA levels, because the HA levels are also elevated (3-5-fold) in bladder tumor tissues (P < 0.001). The profiles of urinary HA species of normal individuals and bladder cancer patients are different. Although only the intermediate-size HA species are found in the urine of normal and low-grade bladder tumor patients, the urine of high-grade bladder cancer patients contains both the high molecular mass and the small angiogenic HA fragments. These urinary HA fragments stimulate a mitogenic response (2.4-fold) in primary human microvessel endothelial cells, suggesting that the small HA fragments may regulate tumor angiogenesis by modulating endothelial cell functions.