Influence of pentobarbital-Na on stimulation-evoked catecholamine secretion in the perfused rat adrenal gland

The relationship between leukocyte migration and parenchymal cell death in vivo remains poorly documented. Accordingly, cell killing in the rat mesentery, as recorded by propidium iodide staining, was investigated with an intravital approach. Superfusion of platelet-activating factor (PAF, 10(-8) M) or N-formyl-methionyl-leucyl-phenylalanine (fMLP, 10(-8) M) led to extensive leukocyte extravasation but no significant cell death. In contrast, pretreatment with 10(-8) M PAF or fMLP for 1 h, followed by superfusion of PAF in combination with fMLP (both at 10(-8) M) led to an increase in cell death. Mesenteric parenchymal cells but no endothelial cells were killed. Some of the dead cells were identified as granulocytes/monocytes that were already in the tissue at the start of the experiment. The incidence of cell death was lower but not eliminated when leukocyte migration was blocked with a monoclonal antibody against CD18. A xanthine oxidase inhibitor, BOF-4272, failed to diminish cell death, whereas a hydroxyl radical scavenger, dimethylthiourea, attenuated cell killing without an effect on the number of adhering and migrating leukocytes. These observations demonstrate that leukocytes serve as a factor in the killing of extravascular cells only after the development of a level of stimulation that differs from that required to induce a migratory stimulus into the extravascular space.     

Effect of renal insufficiency on outcome following infrarenal aortic surgery

The molecular form and subcellular distribution of acid beta-galactosidase in cultured fibroblasts from patients with beta-galactosidase deficiency (GM1-gangliosidosis, Morquio B disease and galactosialidosis) were studied, using antibodies against three different forms of the human enzyme: a high-molecular-weight multienzymic complex, a recombinant 84-kDa precursor, and a 64-kDa tryptic product of the precursor. The mature enzyme from normal fibroblasts was immunoprecipitated by the anti-complex and anti-64-kDa protein antibodies, but not by the anti-84-kDa precursor one. immunofluorescence staining of normal fibroblasts revealed the granular (lysosomal) distribution with anti-64-kDa protein antibody and the perinuclear reticular distribution with anti-84-kDa precursor antibody, probably representing the Golgi apparatus. Both patterns were demonstrated in Morquio B disease, but the residual enzyme activity was exclusively due to the mature enzyme. In Type 1 galactosialidosis, most of the expressed enzyme was detected as the precursor form with a perinuclear reticular distribution. In type 2 galactosialidosis, more than half of the enzyme activity was due to the mature form with a lysosomal distribution. Fibroblasts from a patient with GM1 gangliosidosis, expressing no beta-galactosidase mRNA, did not react against either anti-64-kDa protein antibody or anti-84-kDa precursor antibody. The combined use of immunoprecipitation and immunostaining was useful for analysing the pathophysiology of the intracellular processing and transport of the mutant beta-galactosidase.     

Patient treatment choice and compliance. Data from a substance abuse treatment program

Conservative surgery (CS) is widely accepted today as the treatment of choice for 60 to 80% of the primary breast cancer. Esthetic results of CS are not good in all the cases and improvement can be obtained thanks to the remodelling of the breast after tumorectomy. The scar should be selected according to the location of the tumor; the glandular tissue should be reshaped using local glandular flaps or following the principles of the reduction mammaplasties. Tumorectomy located in the upper part of the gland can be reshaped with an inferior pedicle type of mammoplasty. Defect located in the inferior part of the gland can be reconstructed with a superior pedicle mammoplasty. These sophisticated tumorectomies are providing good esthetic results on the reconstructed breast but require commonly a symmetry procedure on the contralateral breast. Such contralateral reduction allows a better exploration of the opposite breast and histological examination of the reduction specimen. In a series of 76 CS performed at the European Institute of Oncology (IEO), which were associated with some kind of plastic procedure to lower the risk of bad cosmetic results (representing 25% of the CS associated with plastic surgery), we confirmed the value of the mixed oncologic and plastic approach. The esthetic results observed in this series are better than those observed in another series previously published at the Gustave-Roussy Institute (IGR)--good results: 72% (IEO) vs 50% (IGR), and bad results: 6% (IEO) vs 20% (IGR). Statistically such comparison can be criticised, specially because of the short follow-up of the Milan series. However, the difference is rather important if we consider that the series of Milan was a selection of cases with poor esthetic expectation (25% of all the CS performed during the same period), while the series of Paris did not select the patients in what concerns the risk of poor esthetic result.     

Infections in craniofacial surgery: a combined report of 567 procedures from two centers

This retrospective review of infectious complications was undertaken at two craniofacial centers (Dallas and Philadelphia). Fourteen infections were identified over a 6.5-year period in 567 intracranial procedures primarily for craniosynostosis. There were no infections in infants under 13 months of age and no cases of meningitis. The overall infection rate was 2.5 percent, and 85 percent of infections occurred in secondary reoperative cases. Tracheostomies were not identified as a risk factor for infection. No difference was found in infection rates between patients with shaved and unshaved scalps. Candida and Pseudomonas were the two most common organisms identified, and 28 percent of our infections involved yeast. The average time to diagnose infection was 11.5 days (excluding three patients who averaged 5 months). Thirteen of the fourteen infections were treated surgically with placement of a subgaleal irrigation/drainage system. Initial bony debridement was kept to a minimum. Based on our findings, recommendations are made to further lower infection rates, particularly those caused by opportunistic organisms.     

Regeneration of adult axons in white matter tracts of the central nervous system

It is widely accepted that the adult mammalian central nervous system (CNS) is unable to regenerate axons. In addition to physical or molecular barriers presented by glial scarring at the lesion site, it has been suggested that the normal myelinated CNS environment contains potent growth inhibitors or lacks growth-promoting molecules. Here we investigate whether adult CNS white matter can support long-distance regeneration of adult axons in the absence of glial scarring, by using a microtransplantation technique that minimizes scarring to inject minute volumes of dissociated adult rat dorsal root ganglia directly into adult rat CNS pathways. This atraumatic injection procedure allowed considerable numbers of regenerating adult axons immediate access to the host glial terrain, where we found that they rapidly extended for long distances in white matter, eventually invading grey matter. Abortive regeneration correlated precisely with increased levels of proteoglycans within the extracellular matrix at the transplant interface, whereas successfully regenerating transplants were associated with minimal upregulation of these molecules. Our results demonstrate, to our knowledge for the first time, that reactive glial extracellular matrix at the lesion site is directly associated with failure of axon regrowth in vivo, and that adult myelinated white matter tracts beyond the glial scar can be highly permissive for regeneration.     

Anxiety and depression in adolescent cancer: findings in patients and parents at the time of diagnosis

Adolescent cancer is uncommon and presents an exceptional stress for the young patient and their parents. The emotional needs of adolescents with cancer are a major factor in the recommendation for the establishment of adolescent cancer units in major cancer centres in the U.K. However, there have been no prospective, longitudinal studies assessing the psychological impact of a diagnosis of cancer on the adolescent patient and their family. In 1994 we began a longitudinal study of the emotional impact of the diagnosis of cancer in patients and their families presenting to an adolescent cancer unit and of the coping strategies they employ. This first report presents the results of the study at the time of diagnosis in 42 adolescents, 34 mothers and 27 fathers. The Beck Depression Inventory (BDI) was used to assess depression and anxiety levels were measured using Spielberger's State Trait Anxiety Inventory (STAI). Adolescents and their parents completed the questionnaires on first admission to the adolescent cancer unit. The median time since cancer diagnosis was approximately 3 weeks. To provide normative data for the U.K. adolescent population, control values were obtained from 173 pupils of the same age and background. The results showed that, contrary to expectation, adolescents with cancer were no more anxious or depressed than the control adolescent population. Nevertheless, a substantial minority of patients and controls had elevated anxiety or depression scores. Girls were significantly more anxious (P = 0.011) and depressed (P < 0.0001) than boys. Mothers were the most anxious family members and were significantly more anxious than fathers (P = 0.038). Parental anxiety scores, especially mothers, were much higher than reported norms. There was no significant difference between mothers' and fathers' depression scores. Although at the time of diagnosis adolescent cancer patients are not more anxious or depressed than their healthy peers, many adolescents without cancer are anxious or depressed. Staff on adolescent cancer units should therefore be aware of the frequency of emotional disturbance in this population. Mothers are the most anxious family members. Although the findings are relatively reassuring at the time of diagnosis, follow-up data from this cohort will show whether anxiety and depression change with treatment involving intensive chemotherapy, surgery and radiotherapy and will indicate the coping strategies which patients and their families adopt in dealing with both the disease and its treatment.     

A 1.4 A crystal structure for the hypoxanthine phosphoribosyltransferase of Trypanosoma cruzi

The hypoxanthine phosphoribosyltransferase (HPRT) from Trypanosoma cruzi, etiologic agent of Chagas' disease, was cocrystallized with the inosine analogue Formycin B (FmB) and the structure determined to 1.4 A resolution. This is the highest resolution structure yet reported for a phosphoribosyltransferase (PRT), and the asymmetric unit of the crystal contains a dimer of closely associated, nearly identical subunits. A conserved nonproline cis peptide in one active-site loop exposes the main-chain nitrogen to the enzyme active site, while the adjacent lysine side chain interacts with the other subunit of the dimer, thereby providing a possible mechanism for communication between the subunits and their active sites. The three-dimensional coordinates for the invariant Ser103-Tyr104 dipeptide are reported here for the first time. These are the only highly conserved residues in a second active-site loop, termed the long flexible loop, which is predicted to close over the active site of HPRTs to protect a labile transition state [Eads et al. (1994) Cell 78, 325-334]. This structure represents a major step forward in efforts to design/discover potent selective inhibitors of the HPRT of T. cruzi.     

Estradiol protects against ischemic injury

Clinical studies demonstrate that estrogen replacement therapy in postmenopausal women may enhance cognitive function and reduce neurodegeneration associated with Alzheimer's disease and stroke. This study assesses whether physiologic levels of estradiol prevent brain injury in an in vivo model of permanent focal ischemia. Sprague-Dawley rats were ovariectomized; they then were implanted, immediately or at the onset of ischemia, with capsules that produced physiologically low or physiologically high 17beta-estradiol levels in serum (10 or 60 pg/mL, respectively). One week after ovariectomy, ischemia was induced. Estradiol pretreatment significantly reduced overall infarct volume compared with oil-pretreated controls (mean+/-SD: oil = 241+/-88; low = 139+/-91; high = 132+/-88 mm3); this protective effect was regionally specific to the cortex, since no protection was observed in the striatum. Baseline and ischemic regional CBF did not differ between oil and estradiol pretreated rats, as measured by laser Doppler flowmetry. Acute estradiol treatment did not protect against ischemic injury. Our finding that estradiol pretreatment reduces injury demonstrates that physiologic levels of estradiol can protect against neurodegeneration.     

Inhibition of neutrophil apoptosis and modulation of the inflammatory response by granulocyte colony-stimulating factor in healthy and ethanol-treated human volunteers

Nitrogen dioxide levels were measured in 80 homes in the Latrobe Valley, Victoria, Australia, using passive samplers. Some 148 children between 7 and 14 yr of age were recruited as study participants, 53 of whom had asthma. Health outcomes for the children were studied using a respiratory questionnaire, skin prick tests, and peak flow measurements. Nitrogen dioxide concentrations were low, with an indoor median of 11.6 microgram/m3 (6.0 ppb), and a maximum of 246 microgram/m3 (128 ppb). Respiratory symptoms were more common in children exposed to a gas stove (odds ratio 2.3 [95% CI 1. 0-5.2], adjusted for parental allergy, parental asthma, and sex). Nitrogen dioxide exposure was a marginal risk factor for respiratory symptoms, with a dose-response association present (p = 0.09). Gas stove exposure was a significant risk factor for respiratory symptoms even after adjusting for nitrogen dioxide levels (odds ratio 2.2 [1.0-4.8]), suggesting an additional risk apart from the average nitrogen dioxide exposure associated with gas stove use. Atopic children tended to have a greater risk of respiratory symptoms compared with nonatopic children with exposure to gas stoves or nitrogen dioxide, but the difference was not significant.