Community-acquired pneumonia in southeast Asia: the microbial differences between ambulatory and hospitalized patients

STUDY OBJECTIVES: To determine microbial agents causing community-acquired pneumonia (CAP) in Southeast Asia. DESIGN: A prospective study. SETTING: Three general hospitals in Thailand. PATIENTS: Two hundred forty-five adult patients fulfilling the clinical criteria of CAP from September 1998 to April 2001. INTERVENTIONS: Investigations included sputum Gram stain and culture, blood culture, pleural fluid culture (if presented), urine antigen for Legionella pneumophila and Streptococcus pneumoniae, and serology for Mycoplasma pneumoniae, Chlamydia pneumoniae, and L pneumophila. RESULTS: There were 98 outpatients and 147 hospitalized patients included in the study, and an organism was identified in 74 of 98 outpatients (75.5%) and 105 of 147 of the hospitalized patients (71.4%). C pneumoniae (36.7%), M pneumoniae (29.6%), and S pneumoniae (13.3%) were the most frequent causative pathogens found in outpatients, while S pneumoniae (22.4%) and C pneumoniae (16.3%) were the most common in hospitalized patients. There was a significantly higher incidence of C pneumoniae (36.7% vs 16.3%, respectively; p < 0.001) and M pneumoniae (29.6% vs 6.8%; p < 0.001, respectively) in the outpatients than in the hospitalized patients. The incidence of S pneumoniae, L pneumophila, and mixed infections was not different between the groups. Mixed infections were presented in 13 of 98 outpatients (13.3%) and 9 of 147 hospitalized patients (6.1%), with C pneumoniae being the most frequent coinfecting pathogen. CONCLUSIONS: The data indicate that the core organisms causing CAP in Southeast Asia are not different from those in the Western countries. The guidelines for the treatment of patients with CAP, therefore, should be the same.     

Nociceptin/orphanin FQ modulates cortical activity and trigeminal nociception

(Headache 2011;51:1245‐1253) Background.— Alterations in the levels of nociceptin/orphanin FQ (N/OFQ) have been reported in patients with primary headaches, including migraines and cluster headaches. These clinical observations suggest that N/OFQ is involved in the pathogenesis of primary headaches. Objectives.— The present study was conducted to determine the role of N/OFQ in the control of trigeminal nociception and cortical excitation. Methods.— Cortical spreading depression (CSD) was elicited in Wistar rats by cortical application of potassium chloride, and electrocorticograms were recorded. N/OFQ was administered via an intracisternal injection. The presence of CSD‐evoked trigeminal nociception was determined with Fos and transient receptor potential vanilloid 1 (TRPV1) immunoreactivity. Results.— Nociceptin/orphanin FQ produced a biphasic effect on CSD generation, characterized by an initial attenuation followed by delayed potentiation. The amplitude of CSD waves were lower in the initial period but increased in the later period. The total number of CSD waves recorded in 1 hour was greater in the N/OFQ‐treated group. Exposure to N/OFQ significantly increased the number of Fos‐immunoreactive cells in the trigeminal nucleus caudalis and the number of TRPV1‐immunoreactive cells in the trigeminal ganglia, indicating the enhancement of trigeminal nociception. Conclusion.— These results indicate that N/OFQ can lead to biphasic effect characterized by an initial inhibition, and delay potentiation that eventually intensify CSD‐evoked trigeminal nociception.     

Potential risk factors for psychiatric disorders in patients with headache

Background.— Psychiatric comorbidities are common among patients with headache. These can compromise the quality of life of patients and may affect the result of treatment. No available systematic study concerning this problem has been conducted in Thailand. Objective.— The study aimed to determine the prevalence and risk factors of psychiatric disorders in patients with headache in tertiary care facility. Methods.— The study was conducted at the Headache Clinic, King Chulalongkorn Memorial Hospital in Bangkok, Thailand. One hundred and thirteen patients were enrolled. Diagnosis of headache was made based on International Classification of Headache Disorders II system. Mental disorders were assessed using Primary Care Evaluation of Mental Disorders. Other possible risk factors were extracted using significant physical symptoms count and accumulated risk for mental disorder. Results.— Of the 113 samples analyzed, the prevalence of depression, anxiety, and somatoform disorder was found to be 29.2%, 9.7%, and 27.4%, respectively. No definite relationship between headache types and mental disorders was observed. High number of significant physical complaints and health concerns significantly increased the risk for depression (OR = 4.6, 95% CI = 1.6 to 13.5) while the level of possible risk for mental disorder was associated with an increased risk for somatoform disorder (OR = 1.6, 95% CI = 1.2 to 2.2). Conclusion.— The study confirmed high prevalence of psychiatric comorbidities in patients with headache. The results of this study will raise the awareness of physicians to possible underlying mental disorders in patients with headache and facilitate appropriate treatment or psychiatric referral.     

Prevalence and Clinical Features of Chronic Daily Headache in a Headache Clinic

Although chronic daily headache is regarded as a syndrome encountered in headache clinics, clinical characteristics have only rarely been studied and the condition has not been documented in Thailand. To investigate the prevalence as well as clinical features of chronic daily headache in Thai patients, 220 patients visiting Chulalongkorn Headache Clinic were examined. Sixty cases (27.3%) were diagnosed as suffering from chronic daily headache (male to female ratio, 1:5.7).
The average age of these patients was 32.7 ± 9.6 years. Based on the International Headache Society (IHS) criteria, 30% of patients with chronic daily headache could be diagnosed as suffering from migraine end 36.7% from chronic tension-type headache, whereas the remainder had combined features of both headache types and were not classifiable. Diffuse steady pain was the most common headache type reported (65%), however, associated features characteristic of migraine were often noted. These included photophobia (70%), phonophobia (56.7%) and nausea (43%). Thirty-four cases (56.7%) reported that their headache could be aggravated by stress. Daily use of analgesics was reported in 58.3% of cases. We concluded that chronic daily headache is a common problem. Although the mechanism has not been fully clarified, the prevalence of associated psychological factors and analgesic overuse imply their involvement in the pathogenesis of this condition. The criteria of the IHS are not entirely suitable for diagnosis and classification of this disorder, and modification of this classification system is needed.     

Virus-specific CD8+ T Lymphocytes Downregulate T Helper Cell Type 2 Cytokine Secretion and Pulmonary Eosinophilia during Experimental Murine Respiratory Syncytial Virus Infection

T lymphocytes play a pivotal role in the immune response during viral infections. In a murine model of experimental respiratory syncytial virus (RSV) infection, mice sensitized to either of the two major glycoproteins of RSV develop distinct patterns of cytokine secretion and lung inflammation upon subsequent RSV infection. Mice sensitized to RSV-G (attachment) glycoprotein exhibit a strong interleukin (IL)-4 and IL-5 response and develop pulmonary eosinophilia, whereas mice sensitized to RSV-F (fusion) glycoprotein develop a predominantly T helper cell (Th)1 response and pulmonary inflammation characterized by mononuclear cell infiltration. In this study, we examined the potential role of virus-specific CD8⁺ T cytolytic T cells on the differentiation and activation of functionally distinct CD4⁺ T cells specific to these viral glycoproteins. Mice primed with recombinant vaccinia virus expressing RSV-F glycoprotein mounted a strong RSV-specific, MHC class I–restricted cytolytic response, whereas priming with recombinant vaccinia virus expressing RSV-G glycoprotein failed to elicit any detectable cytolytic response. Priming for a RSV-specific CD8⁺ T cell response, either with a recombinant vaccinia virus expressing RSV-G glycoprotein in which a strong CD8⁺ T cell epitope from RSV-M2 (matrix) protein has been inserted or with a combination of vaccinia virus expressing the matrix protein and the RSV-G glycoprotein, suppressed the eosinophil recruitment into the lungs of these mice upon subsequent challenge with RSV. This reduction in pulmonary eosinophilia correlated with the suppression of Th2 type cytokine production. The importance of CD8⁺ T cells in this process was further supported by the results in CD8⁺ T cell deficient, β₂ microglobulin KO mice. In these mice, priming to RSV-F glycoprotein (which in normal mice primed for a strong cytolytic response and a pulmonary infiltrate consisting primarily of mononuclear cells on RSV challenge) resulted in the development of marked pulmonary eosinophilia that was not seen in mice with an intact CD8⁺ T cell compartment. These results indicate that CD8⁺ T cells may play an important role in the regulation of the differentiation and activation of Th2 CD4⁺ T cells as well as the recruitment of eosinophils into the lungs during RSV infection.Multiple arms of the immune system are activated in response to infection by foreign organisms. The outcomes of the infection, such as the clearance of the organisms and the generation of tissue injury, depend on these immune effector mechanisms that are mobilized against the pathogen. The role of T cells in the immune response to viral infections has been clearly established (1, 2). Mature T cells that express α/β T cell receptors can be divided into cells expressing either CD4 or CD8 surface antigen. CD8⁺ T cells recognize processed antigen in the context of MHC class I molecules, whereas CD4⁺ T cells recognize peptides in the context of MHC class II molecules (3, 4). The conventional view of CD8⁺ T cells has been primarily the killing of virally infected cells by direct cytolysis or by cytokines secreted by these T cells such as IFN-γ and TNF (1, 2). Functional subsets of CD4⁺ T cells have been described based on the cytokines produced by these cells, Th1 CD4⁺ T cells that secrete IL-2 and IFN-γ and Th2 T cells that secrete IL-4 and IL-5 (5, 6). The physiological relevance of these subsets of T cells with diverse functions have been shown in several models of viral infection including respiratory syncytial virus (RSV)¹.In the murine model of RSV infection, the roles of T cells and their products in the eradication of the virus as well as the pathogenesis of lung inflammation have been well documented (7–12). Recent studies have shown that mice sensitized to either of the two major glycoproteins of this virus developed distinct lung pathology when subsequently infected with RSV (12–15). Mice sensitized to the attachment glycoprotein (G) of RSV developed pulmonary eosinophilia that correlated with a strong induction of Th2 type response, whereas mice primed to the fusion (F) glycoprotein mounted a weak Th2 response and developed lung inflammation characterized by mononuclear cell infiltration. The underlying mechanisms that lead to these apparent distinct patterns of cytokine production and lung injury still remain unclear.The process by which CD4⁺ T cells mature and differentiate has been the subject of intense investigation (16). CD4⁺ T cells can be induced to differentiate into effector cells of either the Th1 or Th2 subsets, depending on the milieu in which these cells are activated. Cytokines such as IL-4 and IL-12 have been shown to play a crucial part in the regulation of CD4⁺ T cell differentiation (17–19). The presence of certain immune effector functions during the differentiation and expansion of CD4⁺ T cells may potentially be a key factor in determining the functional phenotypes acquired by these cells. In the murine model of experimental RSV infection, one important difference in the immune response to F and G glycoprotein of RSV is the lack of MHC class I–restricted cytolytic response to the G glycoprotein (13, 20). In the following studies, we began to investigate the impact of CD8⁺ T cells and MHC class I–restricted CTL responses on cytokine secretion and the subsequent development of pulmonary eosinophilia during experimental murine RSV infection. We have found that the induction of CD8⁺ T cell response to RSV proteins resulted in dramatically decreased levels of Th2 type cytokines and eosinophil recruitment into the lungs of RSV-infected mice previously sensitized to the RSV-G glycoprotein. The possible mechanisms underlying these observations and their potential significance are discussed.     

Pathophysiology of Medication-overuse Headache: Implications from Animal Studies

Recent animal experiments have shown that chronic medication exposure profoundly affects the function of several areas in the nervous system related to headache pathogenesis. These changes include upregulation of calcitonin gene–related peptide, substance P, and nitric oxide synthase in trigeminal ganglia; expansion of receptive field and decreased nociceptive threshold of central trigeminal neurons; decrease in diffuse noxious inhibitory control; and increased susceptibility to develop cortical spreading depression (CSD). These changes indicate an increase in excitability of cortical and trigeminal neurons. The neuronal hyperexcitability may be the result of derangement of a central, possibly serotonin (5-HT)-dependent, modulating control system. Experiments with animals with low 5-HT showed that the processes of CSD and trigeminal nociception are enhanced in this condition. Derangement in the central 5-HT–dependent modulating system as a result of chronic medication use may underlie the chronification of headache as observed in patients with medication-overuse headache.     

The benefit of curative liver resection with a selective bile duct preserving approach for hepatocellular carcinoma with macroscopic bile duct tumor thrombus

BackgroundHepatocellular carcinoma (HCC) presenting with macroscopic bile duct tumor thrombus (BDTT) is an uncommon event. The role of a curative hepatic resection and associated long-term outcomes remain controversial. In addition the necessity for bile duct resection is still unclear. The aim of this study was to evaluate outcomes of hepatectomy with a selective bile duct preservation approach for HCC with BDTT in comparison to outcomes without BDTT.MethodsA total of 22 HCC with BDTT patients who had undergone curative hepatic resection with a selective bile duct preservation approach at our institute were retrospectively reviewed. These were compared to group of 145 HCC without BDTT patients. The impact of curative surgical resection and BDTT on clinical outcomes and survival after surgical resection were analyzed.ResultsAll HCC with BDTT cases underwent major hepatectomy vs. 32.4% in the comparative group. Bile duct preservation rate was 56.5%. The 1-, 3- and 5-year survival rates of HCC with BDTT patients in comparison to the HCC without BDTT group were 81.8%, 52.8% and 52.8% vs. 73.6%, 55.6% and 40.7% (P=0.804) respectively. Positive resection margin, tumor size ≥5 cm and AFP ≥200 IU/mL were significant risk factors regarding overall survival. However, it is unclear whether presence of a bile duct tumor thrombus has an adverse impact on either recurrence free survival or overall survival.ConclusionsBile duct obstruction from tumor thrombus did not necessarily indicate an advanced form of disease. Tumor size and AFP had greater impact on long-term outcomes than bile duct tumor thrombus. Major liver resection with a selective bile duct preserving approach in HCC with BDTT can achieve favorable outcomes comparable to those of HCC without BDTT in selected patients.     

Computer-aided endoscopic sinus surgery

Objectives: To examine four different types of computer-aided endoscopic sinus surgical devices—the ISG Viewing Wand, the ISG infrared OptoTrak, the IGT FlashPoint 5000, and the VTI InstaTrak—with emphasis on their accuracy and ease of use. Study Design: Prospective study utilizing laboratory experiments and intraoperative data collection. Methods: A review of the literature is presented. Patients undergoing endoscopic sinus surgery during the study period were enlisted under FDA protocols with IRB consent. Groups of patients had surgery performed with each of the above devices—except the FlashPoint 5000. Accuracy measurements were recorded, and user and operating staff comments about ease of use were collected. The FlashPoint 5000 was used exclusively in the laboratory setting, where accuracy measurements were obtained on a cadaver skull. Results: The systems all demonstrated accuracy to within 2.00 mm. Ease of use was somewhat variable, but following a learning curve by the surgeon and operating department personnel, all of the units were considered to be relatively user friendly. Conclusions: Computer-aided endoscopic sinus surgery appears to be the wave of the future. Nevertheless, the modern endoscopic sinus surgeon must have thorough training in the basic anatomy of the paranasal sinuses as well as the various surgical techniques.     

Distinct activation phenotype of a highly conserved novel HLA‐B57‐restricted epitope during dengue virus infection

Variation in the sequence of T‐cell epitopes between dengue virus (DENV) serotypes is believed to alter memory T‐cell responses during second heterologous infections. We identified a highly conserved, novel, HLA‐B57‐restricted epitope on the DENV NS1 protein. We predicted higher frequencies of B57‐NS1_26–34‐specific CD8⁺ T cells in peripheral blood mononuclear cells from individuals undergoing secondary rather than primary DENV infection. However, high tetramer‐positive T‐cell frequencies during acute infection were seen in only one of nine subjects with secondary infection. B57‐NS1_26–34‐specific and other DENV epitope‐specific CD8⁺ T cells, as well as total CD8⁺ T cells, expressed an activated phenotype (CD69⁺ and/or CD38⁺) during acute infection. In contrast, expression of CD71 was largely limited to DENV epitope‐specific CD8⁺ T cells. In vitro stimulation of cell lines indicated that CD71 expression was differentially sensitive to stimulation by homologous and heterologous variant peptides. CD71 may represent a useful marker of antigen‐specific T‐cell activation.