Transection of the origin of the innominate artery: A rare sequela of blunt traumatic chest trauma.

Blunt traumatic transection of the innominate artery is rare. We describe a case of a 36-year-old male who presented to our Emergency & Trauma Center after being struck by a motor vehicle at high speed. Computerised Tomography (CT) scanning after the patient was stabilised facilitated the prompt diagnosis of the injury. The patient underwent open repair by midline sternotomy, with debranching of the innominate artery, using hypothermic circulatory arrest as a neuroprotective measure. The patient was successfully extubated on post-operative day 3, without neurological deficit. We provide our experience as an option for treating any patient that presents with such an injury.

Effect of natural "micronized" progesterone on the chorionic gonadotropin concentrations in cyst fluids of women with gross cystic breast disease.

Gross cystic breast disease (GCBD) is common in women, especially in the age range between 35 and the menopausal years. The present study examined the possible role of progesterone (Pg) in the chorionic gonadotropin (hCG) concentration in GCBD. The breast cyst fluids (BCFs) were drawn by fine needle aspiration between the sixth and the eighth day of the menstrual cycle and twenty days later. On the day of the first aspiration the patient began to take 100 mg of natural micronized Pg orally until the second aspiration. At both times blood samples were also taken. Determinations were done of both BCFs and blood sample using two fully automated chemiluminiscent enzyme immunometric assays. Pg has been demonstrated to induce a significant increment in hCG + free ss-hCG (median, range): 0.27 ng/ml, 0.12-6.24 vs. 1.92 ng/ml, 0.12-423.5; free ss-hCG: 0.11 ng/ml, 0.02-2.40 vs. 0.91 ng/ml, 0.02-58.40 in the BCFs, with no change in the circulating concentrations of the hormone. None of the sera studied presented levels of hCG + free ss-hCG or free ss-hCG above 0.5 ng/ml or 0.1 ng/ml, respectively. The occurrence of hCG or a derivative polypeptide in BCFs, when they are present in high concentrations suggests that this glycoprotein could be synthesized in situ and possibly involved in the pathogenesis of GCBD by the degree of differentiation of breast epithelial cells induced by the hormone.

Palladium and Raney nickel catalyzed methanolic cleavage of stable borane-amine complexes.

[figure: see text] Palladium and Raney nickel were found to catalyze the methanolysis of borane-amine adducts. Hence, strongly complexed amines can now be liberated by simple treatment with Pd/C or Raney Ni in methanol. The method is applicable to primary, secondary, tertiary, and aromatic amines, and the mildness of the reaction conditions allows preservation of otherwise labile functional groups.

Osteosarcoma: correlation between radiological and histological changes after intra-arterial chemotherapy.

The statistical correlation between three different radiological methods (conventional radiography, computed tomography and angiography) and tumor necrosis (TN) of the resected specimen have been studied in a series of 31 patients diagnosed with osteosarcoma (OS). They were treated with a multidisciplinary approach including intraarterial and intravenous chemotherapy followed by limb salvage procedures, plus intraoperative radiotherapy and adjuvant chemotherapy. A clear statistical correlation has been obtained between TN and angiography (p = 0.02) and between TN and two specific radiological signs: 'tumoral stain and neovascularity' (p = 0.02) and 'peritumoral fat planes' (p = 0.05). Conventional radiography, computed tomography and other radiological signs studied (nutrient vessel, soft tissue mass and central peripheral calcifications) did not show any significant correlation with TN. These results seem to suggest that angiography is a method to evaluate TN preoperatively and also to define the efficacy of neoadjuvant chemotherapy in OS.

First Report of the Causal Agent of Huanglongbing ("Candidatus Liberibacter asiaticus") in Brazil.

Huanglongbing (ex-greening) disease is one of the most serious diseases of citrus. It is caused by the phloem-limited, gram-negative bacterium "Candidatus Liberibacter spp.". This bacterium is not well characterized mainly because it is still uncultured. There are two known strains, Asian ("Candidatus Liberibacter asiaticus") and African ("Candidatus Liberibacter africanus") that cause severe damage to citrus plants including twig dieback, decline, and death. Symptoms first appear as leaf mottling and chlorosis occurring in one shoot or sector of trees. Later, leaf symptoms resemble nutritional deficiencies (Zn, Ca, and N) that vary depending on the strains, with more severe symptoms caused by "Ca. L. asiaticus". The Asian strains are transmitted by the Asian citrus psyllid (AsCP), Diaphorina citri, which is present in Brazil. The bacterium has been detected in citrus plants in many geographic locations including China, Japan, Thailand, India, the Philippines, the Arabian Peninsula, and Africa. In 2004, plants showing Huanglongbing symptoms were observed in the Araraquara County, a central region of the State of Sao Paulo, the largest citrus-producing area in Brazil. To verify the presence of "Ca. L. spp." in these plants, leaf samples of sweet orange cvs. Hamlin and Valencia were used for DNA extraction and polymerase chain reaction amplification using the specific OI1 and Oi2c primers (1). Amplification of the 16S rDNA was positive for 2 (cvs. Hamlin and Valencia) of 10 analyzed plants. The amplified fragments were cloned and sequenced. The amplicons obtained from both plants showed the same sequence, which differed from "Ca. L. africanus", utilized as the positive control in the amplification experiment (27 divergent bases in 1,160). The sequences were used for BLAST searches, and the results showed identities ranging from 94.71 to 100% with "Ca. L. spp." sequences available at the National Center for Biotechnology Information database (on-line publication). The highest scores were obtained with "Ca. L. asiaticus sequences. These analyses confirmed the presence of such agent in the State of Sao Paulo. To our knowledge, this is the first report of "Ca. L. asiaticus" in Brazil as well as elsewhere in the Americas. The significance of this report relates to the potential damage that this pathogen could cause to the citrus industry in the largest citrus-producing country in the world. It remains unclear how and when the pathogen entered Brazil. Reference: (1) S. Jagoueix et al. Mol. Cell Probes 10:43, 1996.

Assessment of the function and resistance of sternoclavicular ligaments: A biomechanical study in cadavers.

BACKGROUND: Few biomechanical studies have assessed the resistance of the ligamentous structures of the sternoclavicular joint, and none have reproduced the physiological movements of the joint. Determining the structures that are injured in sternoclavicular dislocations is important for the surgical planning of acute or chronic ligament reconstruction. METHODS: Forty-eight joints from 24 human cadavers were studied, and they were divided into 4 groups of 12 joints each (retraction, protraction, depression and elevation). Biomechanical testing assessed primary and secondary failures. The mechanical resistance parameters between movements that occurred on the same plane (depression versus elevation, protraction versus retraction) were compared. RESULTS: The posterior sternoclavicular ligament was the most injured structure during the protraction test, but it was not injured during retraction. The anterior sternoclavicular ligament was the most affected structure during retraction and depression. The costoclavicular ligament was the most affected structure during elevation. Joint resistance was significantly greater during protraction movements when compared to retraction (P<0.05). CONCLUSION: The anterior sternoclavicular ligament was the most affected structure during retraction and depression movements. During protraction, lesions of the posterior sternoclavicular ligament were most frequent during elevation, and the costoclavicular ligament was the most frequently injured ligament. The resistance of the sternoclavicular joint was significantly greater during protraction movement when compared to retraction. LEVEL OF EVIDENCE: IV, basic science, biomechanics, cadaver model.

Anti-inflammatory effects of theophylline: modulation of cytokine production.

BACKGROUND: The basis for the efficacy of theophylline in the treatment of asthma remains enigmatic. Although commonly classified as a bronchodilator, its ability to dilate smooth muscle is considered fairly poor and clinical responses are often independent of bronchodilation. Recent studies have suggested that immunomodulatory activities may contribute to the therapeutic benefit mediated by theophylline. OBJECTIVE: We performed these preliminary studies to determine whether theophylline modulates cytokine production by peripheral blood mononuclear cells. METHODS: Peripheral blood mononuclear cells were obtained from 24 asthmatic subjects and were left in a resting state or stimulated with either mitogens (phytohemagglutinin, lipopolysaccharide) or antigen (tetanus, cat) with or without the additional presence of theophylline (15 micrograms/dL). Supernatants were collected and evaluated for cytokine concentration by ELISA. RESULTS: Theophylline neither inhibited production of allergenic cytokines such as IL-4 nor modulated the repertoire of cytokines produced by TH cells. A statistically significant inhibition of spontaneous interferon-gamma synthesis was observed (24.5 +/- 8.6 to 13.4 +/- 4.2; P < .05). Theophylline did have anti-inflammatory effects on cytokines primarily produced by mononuclear phagocytic cells. Theophylline mediated a slight inhibition of TNF-alpha production (0.26 +/- 0.08 to 0.21 +/- 0.06; P < .05). Theophylline was also associated with a 2.8-fold increase in spontaneous production of the anti-inflammatory cytokine IL-10 (0.35 +/- 0.08 to 0.98 +/- 0.16 ng; P < .01). CONCLUSIONS: A relative absence of IL-10 characterizes the asthmatic airways and may contribute to the development and severity of allergic inflammation. Induction of IL-10 production by theophylline may therefore mitigate inflammation and contribute to the clinical efficacy of this class of medications.

Interleukin-10 regulation in normal subjects and patients with asthma.

Interleukin-10 or cytokine synthesis inhibitory factor has important antiinflammatory activities in immune diseases. We speculated that diminished IL-10 production in asthma would permit the unopposed synthesis of proinflammatory cytokines, contributing to the development and severity of asthma. Our data demonstrate constitutive secretion of IL-10 into bronchoalveolar lavage (BAL) fluid of normal, nonasthmatic subjects (130 +/- 61 pg/ml; n = 8). Asthmatic patients' BAL fluid was characterized by diminished concentrations of IL-10 (9 +/- 18 pg/ml; n = 8; p < 0.01 compared with that of normal subjects). By using the RNA-based polymerase chain reaction, we demonstrated that diminished IL-10 occurred as a result of inhibition of transcription. IL-10 transcription, but not protein, was observed at the time of the late asthmatic response. We speculate that the subsequent appearance of IL-10 protein could contribute to the resolution of the late asthmatic response. Similar to what was observed in the BAL fluid, peripheral blood mononuclear cells of patients with asthma demonstrated decreased spontaneous (0.01 +/- 0.01 ng/ml-asthmatic and 0.09 +/- 0.04 ng/ml-normal; p < 0.05) and stimulated (0.60 +/- 0.22 ng/ml-asthmatic and 1.69 +/- 0.49 ng/ml-normal; p < 0.05) IL-10 production compared with normal subjects. In support of the hypothesis that IL-10 mitigates the development of inflammation, we demonstrated that the addition of a neutralizing anti-IL-10 antibody to resting peripheral blood mononuclear cell cultures of normal subjects stimulated the spontaneous production of interferon-gamma (10.4 +/- 4.3 to 152.4 +/- 23.6 ng/ml; p < 0.01). Finally, we reasoned that corticosteroids might exert at least part of their antiinflammatory activity through the induction of IL-10 secretion. However, methylprednisolone inhibited the lipopolysaccharide-stimulated production of IL-10 (2.34 +/- 0.49 ng/ml IL-10 with lipopolysaccharide alone to 1.11 +/- 0.38 ng/ml in the additional presence of 10(-6) mol/L methylprednisolone; p < 0.05).

Interleukin-10 and transforming growth factor-beta promoter polymorphisms in allergies and asthma.

Interleukin-10 (IL-10) and transforming growth factor beta (TGF-beta) are inhibitory for B and T cells, IgE production, and mast cell proliferation, and they induce apoptosis in eosinophils. These cytokines are therefore candidate genes which could contribute to the development of asthma or allergies. We investigated the hypothesis that polymorphic nucleotides within the IL-10 and TGF-beta gene promoters would link to the expression of allergies and asthma. DNA taken from families with an asthmatic proband was examined for base exchanges by single-stranded conformational polymorphism (SSCP). We demonstrated the presence of a polymorphism in the promoter region of the IL-10 gene and four in the TGF-beta gene promoters (3 in TGF-beta1 and 1 in TGF-beta2). The IL-10 gene polymorphism was a C-to-A exchange 571 base pairs upstream from the translation start site and was present between consensus binding sequences for Sp1 and elevated total serum. This polymorphism was associated with elevated total serum IgE in subjects heterozygotic or homozygotic for this base exchange (p < 0.009). The base exchange at -509 (from the transcription initiation site) in the TGF-beta promoter also linked to elevated total IgE (p < 0.01). This polymorphism represented a C-to-T base exchange which induced a YY1 consensus sequence and is present in a region of the promoter associated with negative transcription regulation.

Chronic fatigue syndrome: identification of distinct subgroups on the basis of allergy and psychologic variables.

BACKGROUND: We investigated a role for allergic inflammation and psychologic parameters in the development of chronic fatigue syndrome (CFS). METHODS: The design was a comparison between subjects with CFS and age- and sex-matched control cohorts. Studies were performed on CFS subjects (n = 18) and control cohorts consisting of normal subjects (n = 11), allergic subjects (n = 14), and individuals with primary depression (n = 12). We quantified cytokines at baseline as cell-associated immunoreactive peptides and as transcripts evaluated by means of semiquantitative RNA-based polymerase chain reactions. Psychologic evaluations included administration of the Diagnostic Interview Schedule, the Structured Clinical Interview, and the Symptom Checklist 90-Revised. RESULTS: Increases in tumor necrosis factor (TNF)-alpha were identified in individual subjects with CFS (50.1 +/- 14.4 pg TNF-alpha per 10(7) peripheral blood mononuclear cells [PBMCs]; mean +/- SEM) and allergic subjects (41.6 +/- 7.6) in comparison with normal subjects (13.1 +/- 8.8) (P < .01 and P < .05, respectively). Similar trends were observed for interferon (IFN)-alpha in allergic subjects (3.0 +/- 1.7 pg/10(7) PBMCs) and subjects with CFS (6.4 +/- 3.4) compared with normal subjects (1.9 +/- 1.4). A significant increase (P < .05) in TNF-alpha transcripts was demonstrated between subjects with CFS and depressed subjects. In contrast to these proinflammatory cytokines, both subjects with CFS (2.6 +/- 1.8 pg/10(7) PBMCs) and allergic subjects (3.4 +/- 2.8) were associated with a statistically significant (P < .01) decrease in IL-10 concentrations compared with normal subjects (60.2 +/- 18.2). As shown in other studies, most of our subjects with CFS were allergic (15 of 18) and therefore presumably demonstrated cytokine gene activation on that basis. The seasonal exacerbation of allergy was associated with a further increase in cellular IFN-alpha (from 2.1 +/- 1.2 to 14.2 +/- 4.5 pg/107 PBMCs; P < .05) but no further modulation of TNF-alpha or IL-10. Similarly, self-reported exacerbations of CFS were associated with a further increase in IFN-alpha (from 2.5 +/- 1.0 to 21.9 +/- 7.8; P < .05) and occurred at times of seasonal exposures to allergens. This linkage does not permit making any definitive conclusions regarding a causative influence of either seasonal allergies or the increase in cellular IFN-alpha with the increase in CFS symptoms. The close association between atopy and CFS led us to speculate that CFS may arise from an abnormal psychologic response to the disordered expression of these proinflammatory and antiinflammatory cytokines. Psychologic variables were predictive of immune status within the CFS sample (65.9% of the variance in immune status; F (3,10) = 6.44, P < .05). Specifically, the absence of a personality disorder but greater endorsement of global psychiatric symptoms was predictive of immune activation. CONCLUSIONS: Most of our subjects with CFS were allergic, and the CFS and allergy cohorts were similar in terms of their immune status. However, the CFS subjects could be discriminated by the distinct psychologic profiles among subjects with and without immune activation. We propose that in at least a large subgroup of subjects with CFS who had allergies, the concomitant influences of immune activation brought on by allergic inflammation in an individual with the appropriate psychologic profile may interact to produce the symptoms of CFS. In a psychologically predisposed individual, symptoms associated with allergic inflammation are recognized as illness.

The influence of diesel exhaust particles on mononuclear phagocytic cell-derived cytokines: IL-10, TGF-beta and IL-1 beta.

Diesel exhaust particles (DEP) are known to modulate the production of cytokines associated with acute and chronic respiratory symptoms and allergic respiratory disease. Tolerance is an important mechanism through which the immune system can maintain nonresponsiveness to common environmental antigens. We examined the effect of DEP on IL-10 and TGF-beta, cytokines produced by macrophages and repressor (Tr-like) lymphocytes which influence tolerance. Human PBMCs (n = 22) were incubated with 1-100 ng/ml of DEP, and suboptimally primed with LPS. IL-10 gene expression was assessed by the S1 nuclease protection assay, and production of IL-10, TGF-beta, TNF-alpha, IL-1 beta and IL-4 stimulated CD23 was evaluated by ELISA after 24 and 48 h. The effect of the order of exposure to DEP and LPS was evaluated on IL-10 protein and mRNA in cells (1) preincubated with LPS followed by DEP, or (2) exposed first to DEP followed by LPS. IL-10 was further evaluated using benzo[a]pyrene and [alpha]naphthoflavone as a surrogate for the polyaromatic hydrocarbons (PAHs) adsorbed to DEP. Control cells were incubated with carbon black, without PAHs. In PBMCs exposed to DEP with LPS, or preincubated with LPS before DEP, IL-10 production and mRNA fall significantly. TGF-beta is similarly suppressed, IL-1 beta secretion is significantly stimulated, and IL-4 stimulated CD23 release rises in the atopic subjects. In contrast, when DEP is added prior to LPS, IL-10 production rises, and IL-1 beta falls to zero. These effects on IL-10 are reproduced with benzo[a]pyrene and reversed by the coaddition of [alpha]naphthoflavone, its known antagonist. The carbon black fraction has no effect on IL-10 production. The effect of DEP on IL-10 can be inhibitory or stimulatory, depending on the order of exposure to DEP and LPS. Pro-inflammatory cytokines and factors rise when IL-10 is inhibited, and are suppressed when IL-10 is stimulated. These results are duplicated with benzo[a]pyrene, suggesting that the PAH portion of the DEP is the active agent.