Abdominal pseudocyst: predisposing factors and treatment algorithm

Abdominal pseudocyst (APC) is an uncommon complication of ventriculoperitoneal shunts. Various predisposing factors have been attributed to it, including the presence of infection and multiple shunt revisions. We reviewed the records of shunt revisions performed over a 20-year period. During that time, 64 cases of APC were found in 36 patients. The records were then reviewed for the presence of infection, history of necrotizing enterocolitis, prior abdominal surgery, and treatment performed. Of the cases of APC, 46 were primary and 18 were recurrent. A history of prior abdominal surgery other than shunt revision was found in 47% of patients and a history of necrotizing enterocolitis was found in 19% of patients. The average number of prior shunt revisions was 4.1 per patient. Shunt infection as defined by positive cultures of either cerebrospinal fluid or abdominal fluid was present in only 23% of cases of APC. A history of prior shunt infection was present in 30% of patients. Infection was treated by shunt removal, external ventricular drainage, and appropriate antibiotics. After the infection was cleared or if no infection was present, treatment consisted of: (1) repositioning the distal catheter into the peritoneum, (2) repositioning the distal catheter into the pleural space, the atrium, or the gallbladder, (3) exploratory laparotomy with lysis of adhesions and repositioning the peritoneal catheter, (4) APC aspiration only, or (5) shunt removal or disconnection. Because of the complexity of APC management, we analyzed the outcomes of our cases and outlined an algorithm to simplify this process.     

Is rheumatoid arthritis a consequence of natural selection for enhanced tuberculosis resistance?

Although the bubonic plague or "Black Death" is notorious for the toll it took on the population of Europe in the middle ages, another epidemic, the "White Death" of tuberculosis is responsible for millions of deaths worldwide over the past 300 years. With one in four deaths due to tuberculosis in Western Europe and the United States in the 19th century, this disease undoubtedly acted as a powerful genetic selective force. The epidemiology of modern day rheumatoid arthritis (RA) is strikingly similar to the epidemiology of tuberculosis 100-200 years ago, suggesting the possibility that genetic factors that enhanced survival in tuberculosis epidemics are now influencing susceptibility to RA. Recent advances in the analysis of genetic polymorphisms associated with disease have identified several genes linked to RA susceptibility that encode proteins involved in the immune response to Mycobacterium tuberculosis infection, including TNF-alpha, NRAMP1, PARP-1, HLA-DRB1, and PADI4. These results suggest that rheumatoid arthritis, and possibly other autoimmune diseases, are modern day manifestations of the genetic selective pressure exerted by tuberculosis epidemics of the recent past.     

Late onset neurodegeneration in the Cln3-/- mouse model of juvenile neuronal ceroid lipofuscinosis is preceded by low level glial activation

Mouse models of neuronal ceroid lipofuscinosis (NCL) exhibit many features of the human disorder, with widespread regional atrophy and significant loss of GABAergic interneurons in the hippocampus and neocortex. Reactive gliosis is a characteristic of all forms of NCL, but it is unclear whether glial activation precedes or is triggered by neuronal loss. To explore this issue we undertook detailed morphological characterization of the Cln3 null mutant (Cln3(-/-)) mouse model of juvenile NCL (JNCL) that revealed a delayed onset neurodegenerative phenotype with no significant regional atrophy, but with widespread loss of hippocampal interneurons that was first evident at 14 months of age. Quantitative image analysis demonstrated upregulation of markers of astrocytic and microglial activation in presymptomatic Cln3(-/-) mice at 5 months of age, many months before significant neuronal loss occurs. These data provide evidence for subtle glial responses early in JNCL pathogenesis.     

Functional inactivation in mice of the gene for the interleukin-3 (IL- 3)-specific receptor beta-chain: implications for IL-3 function and the mechanism of receptor transmodulation in hematopoietic cells

The receptors for granulocyte-macrophage colony-stimulating factor (GM- CSF) and interleukin-3 and -5 (IL-3, IL-5) share a common signaling subunit (beta c). However, in the mouse, IL-3 can also use an alternative IL-3-specific receptor beta-chain (beta IL-3). To assess the relative contributions of beta c and beta IL-3 to IL-3 receptor formation and function, mice were generated in which the beta IL-3 gene was functionally inactivated by replacement of exons 9-13 with a neomycin resistance cassette. Bone marrow cells from these mice displayed a lower affinity IL-3 receptor than normal and were hyporesponsive to IL-3, but the mice displayed no obvious hematopoietic abnormalities. The data suggested that beta c and beta IL-3 are normally coexpressed on IL-3-responsive cells and have identical qualitative signaling capacities. Receptor transmodulation studies on bone marrow cells from wild-type, beta c -/-, and beta IL-3 -/- mice showed that the previously described hierarchical pattern of transmodulation was dependent on the relative numbers of both beta IL-3 and beta c receptor chains and also provided evidence for an unexpected interaction between beta c chains and G-CSF and M-CSF receptors.     

Trophic actions of recombinant human nerve growth factor on cultured rat embryonic CNS cells

NGF is a neurotrophic factor for basal forebrain cholinergic neurons and may serve to counteract the cholinergic deficits that are observed in Alzheimer's disease. Prior to the introduction of clinical trials, it is essential that recombinant human NGF (rhNGF) be produced and that its actions on target cells in the CNS be demonstrated. We prepared rhNGF and examined its actions on fetal rat brain neurons in culture including, in particular, the cholinergic neurons of the basal forebrain. rhNGF was more potent in increasing choline acetyltransferase (ChAT) activity in septal cultures than NGF purified from mouse salivary glands (mNGF). ED50s of the beta-NGF dimers were 4.9 pM for rhNGF and 12.4 pM for mNGF. The maximal ChAT activity response was achieved at approximately 35 pM with both NGFs and their efficacies were not significantly different. The two NGFs were not additive in effect. Identical to the results with mNGF, rhNGF strongly enhanced the intensity of ChAT immunostaining in septal cultures. Neither rhNGF nor mNGF affected the appearance of the cultures under phase-contrast illumination. Survival of cells at very low plating density on polyornithine/laminin-coated culture dishes was not affected by rhNGF or mNGF. Protein content and the uptake of GABA were also unaffected. At concentrations of up to 10 micrograms/ml, rhNGF did not significantly increase uptake of dopamine into cultures of ventral mesencephalon. We conclude that rhNGF produces potent and selective actions on cholinergic neurons of the basal forebrain as previously shown for mNGF.     

Characterization of the carcinogen 2-amino-3,8-dimethylimidazo[4,5- f]quinoxaline in cooking aerosols under domestic conditions

Lung cancer in women is the leading cause of cancer death in Taiwan. Most Chinese women are non-smokers and 60% of female lung cancer patients have adenocarcinomas. Epidemiological data indicate that the incidence of lung cancer among Chinese women may be correlated with cooking fumes. However, the carcinogenic compound(s) in cooking fume aerosols is not defined. In the present study, the cooking aerosols from Chinese stir-frying of fish were prepared under domestic conditions. To determine the mutagenic compounds in the cooking aerosol, mutagens were purified by two steps of high-performance liquid chromatography (HPLC), and their mutagenicity was monitored with Salmonella typhimurium TA98. The mutagen was eluted as a single peak. The chemical structure of the mutagenic fraction of cooking aerosol from frying of fish was characterized by UV spectra and electrospray mass spectrometry. The bacterial indirect-acting mutagenic compound in the cooking aerosol extract was determined to be 2-amino-3,8- dimethylimidazo[4,5-f]quinoxaline (MeIQx). An amount of 0.25 ng MeIQx/g of meat per min was estimated based on the mutagenic response. These data indicated that significant amounts of MeIQx (268.1 ng/Chinese dish of frying fish) were present in cooking aerosol in a short time. Chinese women spend approximately 1 h preparing meals everyday, thus, they may be exposed to significant amounts of MeIQx from cooking aerosols in the kitchen.      

Mouse nerve growth factor prevents degeneration of axotomized basal forebrain cholinergic neurons in the monkey

NGF, a trophic polypeptide, is necessary for the normal development and survival of certain populations of neurons in the CNS and PNS. In the CNS, cholinergic neurons of the basal forebrain magnocellular complex (BFMC) are prominent targets of NGF. During rat development, NGF increases the activity of ChAT in these neurons. In adult rats with experimental injury of axons in the fimbria-fornix, NGF prevents degenerative changes in axotomized cholinergic BFMC neurons in the medial septal nucleus (MSN). Because the amino acid sequences of NGF and its receptor (NGF-R) are highly conserved across species, we hypothesized that mouse NGF would also prevent degeneration of cholinergic BFMC neurons in nonhuman primates. Therefore, the present study was designed to test whether fimbria-fornix lesions result in retrograde degenerative changes in basal forebrain cholinergic neurons in macaques, whether these changes are prevented by mouse NGF, and whether the protective effect of NGF is selective for cholinergic neurons of the basal forebrain. Following unilateral complete transection of the fornix, animals were allowed to survive for 2 weeks, during which time half of the subjects received intraventricular NGF in vehicle and the other half received vehicle alone. In animals receiving vehicle alone, there was a 55% reduction in the number of ChAT-immunoreactive cell bodies within the MSN ipsilateral to the lesion; loss of immunoreactive somata was more severe in caudal planes of the MSN. Remaining immunoreactive neurons appeared smaller than those in control, unoperated animals. In Nissl stains, there was no apparent loss of basophilic profiles in the MSN, but cells showed reduced size and intensity of basophilia. Treatment with NGF almost completely prevented reductions in the number and size of cholinergic neurons and had a significant general effect in preventing atrophy in basophilic magnocellular neurons of the MSN, though some basophilic neurons in the MSN did not appear to respond to NGF. Adjacent 7-microns-thick sections stained with ChAT and NGF-R immunocytochemistry revealed that these markers are strictly colocalized in individual neurons in the MSN in controls and in both groups of experimental animals. Thus, mouse NGF profoundly influences the process of axotomy-induced retrograde degeneration in cholinergic BFMC neurons in primates. The in vivo effectiveness of mouse NGF on primate BFMC neurons suggests that mouse or human recombinant NGF may be useful in ameliorating the ACh-dependent, age-associated memory impairments that occur in nonhuman primates.(ABSTRACT TRUNCATED AT 400 WORDS)     

Neurodevelopment of surviving infants at age two years, with a birthweight less than 2000 g and cared for in neonatal intensive care units (NICU)-results from a population based longitudinal study in Taiwan

All surviving infants from nine neonatal intensive care units (NICU) in a southern city and county of Taiwan were followed up and assessed at 2 y of age if they had a birthweight of less than 2000 g and were born between February 1, 1993 and January 31, 1994. The assessments included: neurological, growth and general health. A comparison group of normal birthweight and full-term infants without congenital anomalies, matched by birth month and sex to the NICU survivors was also studied with respect to the same outcome measures. A developmental delay (either a severe neurological deficit or Mental Development Index <68 or Psychomotor Development Index <68) was present in 21 (15.4%) of the cases, compared to 3 (2.5%) of the controls (P < 0.0004). Significant correlates of developmental outcome for the cases were birthweight, gestational age, and maternal education. The very low birthweight (VLBW) children (<1500 g) in our study cohort had a comparatively higher incidence of severe neurological deficits (and cerebral palsy) than that reported by other similar studies in developed countries. The incidence of abnormal neurodevelopmental outcome remained high in the graduates of NICU at 2 y of age, compared to that in normal controls. The findings have important implications in future health policy making regarding postnatal management of the surviving infants of NICU in developing countries such as Taiwan.