Esophageal perforation: emphasis on management

BACKGROUND: Perforation of the esophagus is a deadly injury that requires expert management for survival. METHODS: We performed a retrospective clinical review of 66 patients treated at Emory University affiliated hospitals for esophageal perforation between 1973 and 1993. RESULTS: Iatrogenic perforations accounted for 48 injuries (73%), barogenic perforations occurred in 12 patients (17%), trauma was causative in 3 (5%), and 3 patients had esophageal infection and other causes. Lower-third injuries occurred in 43 cases (65%), middle third in 14 (21%), and upper third in 9 (14%). Early contained perforations were managed successfully by limiting oral intake and giving parenteral antibiotics in 12 patients. Cervical perforations were drained without attempt at closure of the leak. Perforations with mediastinal or pleural contamination recognized early were managed by primary closure and drainage in 28 patients. Reinforcement of the primary closure using stomach fundus, pleural, diaphragmatic, or pericardial flap was performed in 16 patients. Those perforations that escaped early recognition required thoughtful management, using generous debridement and drainage and sometimes esophageal resection. The esophageal T tube provided control of leaks in 3 of these patients and was a useful adjunct. Using these management principles, we achieved a 76% survival rate for all patients. Six patients with perforations complicating endoesophageal management of esophageal varices were a high-risk subset with an 83% mortality rate. CONCLUSIONS: Esophageal perforation remains an important thoracic emergency. Aggressive operative therapy remains the mainstay for treatment; however, conservative management may be preferred for contained perforations and the esophageal T tube may be used for late perforations.     

Rearrangement of immunoglobulin genes in chicken B cell development

Immunoglobulin gene rearrangement in the chicken has evolved not to generate antibody diversity per se but to generate an immunoglobulin variable region which can be diversified by subsequent somatic gene conversion events. While the molecular mechanism of V(D)J recombination in chickens cannot be distinguished from that seen in other species, the way in which this recombination is regulated during chicken B lymphocyte development does differ from the more widely known models of gene rearrangement in humans and rodents. In this review we focus on these differences, relating V(D)J recombination to the progression of chicken B cell development in the bursa of Fabricius.     

Specificity of dating aggression and its justification among high-risk adolescents

Police investigation records of all suicide cases in 1992 (n = 769) and the suicide notes that had been left (224 notes for 154 subjects) were examined. Note-leavers were characterized as young females, of non-widowed marital status, with no history of previous suicide attempts, no previous psychiatric illness, and with religious beliefs. Suicide notes written by young people were longer, rich in emotions, and often begging for forgiveness. Suicide notes written by the elderly were shorter, contained specific instructions, and were less emotional. A significant proportion of note-leavers did mention their difficulties. Suicide notes may serve some explanatory purpose and may have a therapeutic role in helping the surviving relatives to understand the suicide. A knowledge of the messages contained within suicide notes could be useful for suicide prevention programmes. The significance of suicide notes is best understood within the context of the occurrence of suicides.     

Paracrine expression of a native soluble vascular endothelial growth factor receptor inhibits tumor growth, metastasis, and mortality rate

Vascular endothelial growth factor (VEGF) is a potent and selective vascular endothelial cell mitogen and angiogenic factor. VEGF expression is elevated in a wide variety of solid tumors and is thought to support their growth by enhancing tumor neovascularization. To block VEGF-dependent angiogenesis, tumor cells were transfected with cDNA encoding the native soluble FLT-1 (sFLT-1) truncated VEGF receptor which can function both by sequestering VEGF and, in a dominant negative fashion, by forming inactive heterodimers with membrane-spanning VEGF receptors. Transient transfection of HT-1080 human fibrosarcoma cells with a gene encoding sFLT-1 significantly inhibited their implantation and growth in the lungs of nude mice following i.v. injection and their growth as nodules from cells injected s.c. High sFLT-1 expressing stably transfected HT-1080 clones grew even slower as s.c. tumors. Finally, survival was significantly prolonged in mice injected intracranially with human glioblastoma cells stably transfected with the sflt-1 gene. The ability of sFLT-1 protein to inhibit tumor growth is presumably attributable to its paracrine inhibition of tumor angiogenesis in vivo, since it did not affect tumor cell mitogenesis in vitro. These results not only support VEGF receptors as antiangiogenic targets but also demonstrate that sflt-1 gene therapy might be a feasible approach for inhibiting tumor angiogenesis and growth.     

Mathematical modelling of drug transport in emulsion systems

Two mathematical models for the prediction of drug transport in triphasic (oil, water and micellar) emulsion systems as a function of micellar concentration have been developed and these models were evaluated by comparing experimental and simulated data. Fick's first law was used to derive a transport model for hydrophilic drugs, assuming that the oil/water (o/w) partitioning process was fast compared with membrane transport and therefore drug transport was limited by the membrane. Consecutive rate equations were used to model transport of hydrophobic drugs in emulsion systems assuming that the o/w interface acts as a barrier to drug transport. Benzoic acid and phenol were selected as hydrophilic model drugs. Phenylazoaniline and benzocaine were selected as hydrophobic model drugs. Transport studies at pH 3.0 and 7.0 were conducted using side-by-side diffusion cells. According to the hydrophilic model, an increase in micellar concentration is expected to decrease drug transport rates. The effective permeability coefficients (Peff) of drugs were calculated using an equation relating Peff and the total apparent volume of drug distribution (determined experimentally using drug/membrane permeability and partition coefficient values). The hydrophobic model was fitted to the experimental data for the cumulative amount of model drug in the receiver cells using a weighted least-squares estimation program (PCNONLIN). The oil/continuous phase partitioning rates (k1) and the membrane transport rates (k2) were estimated. The goodness of fit was assessed from the correlation coefficients of plots of predicted versus experimental data. The predicted data were consistent with the experimental data for both the hydrophilic and hydrophobic models.     

Fibrolytic enzyme treatment of barley grain and source of forage in high-grain diets fed to growing cattle

We conducted a study to determine the effects of treating barley grain with a fibrolytic enzyme mixture on chewing activities, ruminal fermentation, and total tract digestibility in cattle. We also investigated the potential benefits of using barley straw rather than barley silage as a roughage source in high-grain diets for feedlot cattle. Steers were given ad libitum access to one of four diets that consisted of 95% barley-based concentrate and 5% forage (DM basis). The concentrate was either control or enzyme-treated, and the forage was either barley silage or barley straw. Applying the enzyme mixture onto the barley lowered the concentrations of dietary ADF and NDF. However, it is not certain when this fiber hydrolysis occurred relative to feed consumption because the fiber analyses were conducted after the study was completed. Enzyme treatment of barley increased total tract dietary ADF digestibility by 28% (P<.05). Acetate-to-propionate ratio tended to decrease, which suggests that enzymes may have increased ruminal starch digestion as a result of enhanced digestion of barley hulls. Replacing silage with straw increased ADF intake (P<.05) and resulted in 1-h/d increase in rumination time (P<.05). Even though there was no effect of diet on ruminal pH, replacing silage with straw increased ruminal acetate, as a percentage of total VFA, and total tract ADF digestion (P<.01). This study demonstrates that using a fibrolytic enzyme mixture in high-grain diets that contain mainly barley grain can improve fiber digestion and grain utilization, but the mode of action is unclear. Straw can be used rather than silage to increase the effective fiber content of a high-grain feedlot diet.     

Enhanced radioresponse of paclitaxel-sensitive and -resistant tumours in vivo

Functional assembly of the plasminogen-dependent proteolytic system on the cell surface requires multiple interactions involving urokinase (uPA), urokinase receptor (uPAR), plasminogen activator inhibitors, and other molecules that mediate cell migration and adhesion. We analyzed the in vitro interaction of uPAR-containing particulate cell fractions with the amino-terminal fragment (ATF) of human urokinase and the matrix-like form of vitronectin. Binding and cross-linking of 125I-labeled ATF to crude membrane extracts from LB6-19 mouse cells overexpressing human uPARs in the presence of 25 nM urea-denatured vitronectin led to the formation of Mr 137,000, 92, 000, and 82,000 covalent complexes. Immunoprecipitation of the preformed cross-linked 125I-labeled complexes with anti-vitronectin, anti-uPA, or anti-uPAR antibodies revealed that the Mr 82,000 and 92, 000 species do contain ATF and vitronectin and identified the Mr 137, 000 species as a ternary complex formed by ATF, uPAR, and vitronectin. A similar electrophoretic pattern was displayed by acid-pretreated membranes extracted from MCF-7 breast carcinoma or HT1080 fibrosarcoma cell lines, as well as a ductal breast carcinoma specimen; the latter exhibited complex formation at concentrations of vitronectin lower than 10 nM. Finally, uPAR-vitronectin interaction was further documented by the decreased reactivity of an anti-uPAR polyclonal antibody to acid-pretreated sections of 10 breast carcinomas that had been preincubated with vitronectin. Our findings highlight the ability of uPAR to interact simultaneously with vitronectin and uPA in breast cancer, supporting a dynamic coupling of the molecular mechanisms underlying plasminogen-dependent matrix degradation and cell adhesion.     

Chronic pain in the lives of older women

We investigated the effect of chlorpromazine (CPZ) in a murine model of T-cell-dependent liver injury caused by concanavalin A (ConA). CPZ (3 and 10 mg/kg) treatment 1 h before ConA injection prevented liver injury. CPZ (3, 10 mg/kg) administered 1 h after a ConA injection was also hepatoprotective, whereas cyclosporin (CsA, 100 mg/kg) was active only when given before ConA. Under either condition, CsA but not CPZ prevented concurrent increases in splenic ornithine decarboxylase (ODC) activity, a putative index of T-cell proliferation/differentiation. CPZ down-regulated tumor necrosis factor-alpha (TNF-alpha) and up-regulated IL-10 in mice that then received ConA, whereas delayed administration of CPZ had no effect. These results suggest that CPZ prevented liver injury without affecting the proliferation/differentiation of T-cells. The dissociation of hepatoprotection by CPZ from cytokine modulation indicates that this drug intervenes in the adherence of T-cells or the death of hepatocytes in the ConA-model.