Is routine pre-entry chest radiograph necessary in a high tuberculosis prevalence country?

CONTEXT: Chest radiographs have been used worldwide as a screening tool before employment and training, by various healthcare and other government and nongovernment institutions. Many studies done in the past have demonstrated a relatively low yield for tuberculosis detection and therefore, the authors have questioned this practice. AIMS: To compare the value of the preadmission/employment chest radiograph in two groups, namely, those who have been previously exposed to a healthcare setting (post-exposure group) and those who have not been exposed (pre-exposure group) and to determine if there is a significant difference in tuberculosis detection between these two groups. SETTINGS AND DESIGN: A retrospective review of the reports of the chest radiographs of all candidates appearing for admission to various undergraduate and postgraduate courses in our institute between 2014 and 2017 was performed. MATERIALS AND METHODS: The various abnormalities detected were recorded and the findings in the two groups were compared. STATISTICAL ANALYSIS USED: Chi-square test was used to compare between two group proportions. RESULTS: Thirty out of 4333 (0.69%) candidates in the pre-exposure group and 53 out of 3379 (1.57%) candidates in the post-exposure group showed abnormalities on chest radiographs involving the lung parenchyma, mediastinum, heart, or pleura. In the pre-exposure group, six (0.14%) were found to have underlying cardiac disease and one (0.02%) had tuberculosis. Among the six candidates in the post-exposure group who underwent further investigations in our institute, five (0.15%) were diagnosed to have tuberculosis. Although there was no statistically significant difference in tuberculosis detection between the groups (P = 0.051), there is a trend towards higher detection of tuberculosis in the post-exposure group. CONCLUSIONS: In a country where the prevalence of tuberculosis is high, the pre-employment chest radiograph may still have a role in detecting tuberculosis in the post-exposure group.

Synergistic effects of A1896, T1653 and T1762/A1764 mutations in genotype c2 hepatitis B virus on development of hepatocellular carcinoma.

The effects of genomic changes in hepatitis B virus (HBV) on the occurrence of hepatocellular carcinoma (HCC) are still unclear, especially in relation to the genotype of HBV. In this study, we examined the effects of genomic changes in HBV of genotype C2 on the development of HCC. A total of 318 patients with HBV-associated HCC and 234 patients with chronic hepatitis B (CHB) were studied. All of HCC cases were diagnosed histologically and treated with surgical resection. The whole of the X, S, basal core promoter (BCP) and precore regions of the viral genome from sera or liver tissues were sequenced. All subjects had HBV of genotype C2. The prevalence of the T1653 mutation in the X region and the A1896 mutation in the precore region of HBV was significantly higher in the HCC group than in the control CHB group (22% vs 11%, P = 0.003; 50% vs 23%, P < 0.001, respectively). Moreover, the T1762/A1764 mutations in the BCP region in combination with either T1653 or A1896 were more common in the HCC compared with the CHB group (BCP+X1653: 18% vs 11%, P = 0.05; BCP+PC, 40% vs 15%, P < 0.001, respectively). In multivariate analysis, T1653 and A1896 were revealed to be independent risk factors for HCC development. G1896A in the precore region and C1653T mutation in the X region of genotype C2 HBV are important risk factors for HCC development. Also, the A1762T/G1764A double mutation may act in synergy with C1653T to increase the risk of HCC in patients chronically infected with HBV genotype C2.

The pathway and targeting signal for delivery of the integral membrane glycoprotein LEP100 to lysosomes.

A complete set of chimeras was made between the lysosomal membrane glycoprotein LEP100 and the plasma membrane-directed vesicular stomatitis virus G protein, combining a glycosylated lumenal or ectodomain, a single transmembrane domain, and a cytosolic carboxyl-terminal domain. These chimeras, the parent molecules, and a truncated form of LEP100 lacking the transmembrane and cytosolic domains were expressed in mouse L cells. Only LEP100 and chimeras that included the cytosolic 11 amino acid carboxyl terminus of LEP100 were targeted to lysosomes. The other chimeras accumulated in the plasma membrane, and truncated LEP100 was secreted. Chimeras that included the extracellular domain of vesicular stomatitis G protein and the carboxyl terminus of LEP100 were targeted to lysosomes and very rapidly degraded. Therefore, in chimera-expressing cells, virtually all the chimeric molecules were newly synthesized and still in the biosynthesis and lysosomal targeting pathways. The behavior of one of these chimeras was studied in detail. After its processing in the Golgi apparatus, the chimera entered the plasma membrane/endosome compartment and rapidly cycled between the plasma membrane and endosomes before going to lysosomes. In pulse-expression experiments, a large population of chimeric molecules was observed to appear transiently in the plasma membrane by immunofluorescence microscopy. Soon after protein synthesis was inhibited, this surface population disappeared. When lysosomal proteolysis was inhibited, chimeric molecules accumulated in lysosomes. These data suggest that the plasma membrane/early endosome compartment is on the pathway to the lysosomal membrane. This explains why mutations that block endocytosis result in the accumulation of lysosomal membrane proteins in the plasma membrane.

High resolution approaches for the identification of amyloid fragments in brain.

BACKGROUND: It is now widely recognized that endogenous, picomolar concentrations of the 42 amino acid long peptide, amyloid-ß (Aß42) is secreted under normal physiological conditions and exerts important functional activity throughout neuronal intracellular compartments. Transgenic animal models that overexpress Aß42 and its precursor, amyloid precursor protein (APP), have not provided predictive value in testing new treatments for Alzheimer's disease (AD), resulting in failed clinical trials. While these results are discouraging, they underscore the need to understand the physiological roles of Aß42 and APP under normal conditions as well as at early pre- symptomatic stages of AD. New method: We describe the use of acrolein-perfusion in immunoelectron microscopy in combination with novel antibodies directed against endogenous murine Aß42 and APP fragments to study abnormalities in the endolysosomal system at early stages of disease. The specific requirements, limitations and advantages of novel antibodies directed against human and murine Aß42, APP and APP fragments are discussed as well as parameters for ultrastructural analysis of endolysosomal compartments. RESULTS: Novel antibodies and a detailed protocol for immunoelectron microscopy using acrolein as a fixative are described. Acrolein is shown to preserve intraneuronal Aß42 species, as opposed to paraformaldehyde fixed tissue, which primarily preserves membrane bound species. Comparison with existing method(s): Technology sensitive enough to detect endogenous Aß42 under physiological conditions has not been widely available. We describe a number of novel and highly sensitive antibodies have recently been developed that may facilitate the analysis of endogenous Aß42. CONCLUSIONS: Using novel and highly specific antibodies in combination with electron microscopy may reveal important information about the timing of aberrant protein accumulation, as well as the progression of abnormalities in the endolysosomal systems that sort and clear these peptides.

Natural killer cell in systemic lupus erythematosus. Defects in effector lytic activity and response to interferon and interferon inducers.

Spontaneous cytotoxicity mediated by natural killer (NK) cells is impaired in several human diseases including systemic lupus erythematosus (SLE). The precise mechanism(s) by which NK activity is suppressed in patients with SLE is generally unknown. The present study was designed to focus on cellular defects per se in NK cells from patients with SLE. It was observed that the usual enhancing effect of interferon (IF) and IF inducers was markedly impaired in SLE patients. Of 24 SLE patients studied, 17 had significantly decreased NK activity relative to controls. NK activity had a significant negative correlation with clinical activity score (r = -0.56, P less than 0.005) but was not correlated with corticosteroid dose, antinuclear antibody titers, total hemolytic complement (CH50), or sedimentation rate. Furthermore, significant depressions in NK activity correlated with variations in disease activity in six patients followed serially. Depressed NK function could not be reversed by prolonged in vitro incubation at 37 degrees C or with protease treatment. Furthermore, depressed NK activity was not altered by removal of glass adherent cells nor was a suppression of NK activity in normal controls seen by the addition of SLE peripheral mononuclear cells. No reversal of depressed activity to normal levels was seen by the addition of indomethacin nor did the supernatants from SLE cell cultures cause a suppression of normal NK function. NK activity in SLE patients did not respond normally to IF inducers (poly-I:C and concanavalin A) even if the SLE patients had normal NK function. The response of SLE cells to exogenous IF was also impaired. The number of effector-target conjugates was quantitated with several target cells (K562, Yac-1, Fravel) in SLE patients and controls. A significant correlation between the proportion of glass nonadherent mononuclear cells that formed effector-target conjugates with these various targets and the magnitude of NK lysis was observed. However, SLE and normal subjects had equal numbers of effector-target conjugates independent of NK function. Release of a soluble cytotoxic factor was induced with concanavalin A, and was markedly impaired in SLE patients relative to normal controls. Thus, impaired NK cell function in SLE does not appear to be related to cell-mediated suppressive mechanisms or to the deletion of effector cells; rather, the decreased NK activity may be related to an impaired release of a soluble cytotoxic factor.

Outbreak of Notozothecium bethae (Monogenea: Dactylogyridae) in Myleus schomburgkii (Actinopterygii: Characiformes) cultured in the Peruvian Amazon.

The presence of Notozothecium bethae was investigated in 76 black band myleus (Myleus schomburgkii [Actinopterygii: Charasiformes]) born and kept in captivity in two semi-intensive breeding cages in the northern region of Peru. Among the 76 cultivated specimens of M. schomburgkii examined in the present study, 100 % had monogenean on the gill and the parasites were identified as Notozothecium bethae. During the survey no bacteria was isolated, and no protozoan or other metazoan parasites were found. The prevalence of N. bethae remained constant throughout the present study. Mean intensity of N. bethae in the months of April and May was exceptionally high in both facilities. The massive infection of N. bethae on the gills of M. schomburgkii was associated with mortality. This is the first report of N. bethae in M. schomburgkii born in captivity and cultured in the Amazon region. The mortality due the presence of this parasite emphasise the need for disease control strategies of cultured M. schomburgkii.

Spontaneously occurring antibodies to parathyroid hormone.

A 76-yr-old female with acute pancreatitis and a normal/borderline elevated serum calcium level was found to have an elevated immunoreactive circulating PTH concentration using a C-terminal assay. This high PTH concentration misled the attending physicians and resulted, in retrospect, in an unnecessary neck exploration. When the patient's serum was examined it was found to contain a binding component that bound both C-terminal and PTH-(1-84). This binding component was not retained on a Sep-Pak column and was precipitated by antiserum directed against human immunoglobulin M. The presence of circulating anti-PTH immunoglobulin M explains the apparently high PTH concentrations measured by RIA. The antibodies occurred spontaneously. To the best of our knowledge, this phenomenon has not previously been described.

Normal brain development in PS1 hypomorphic mice with markedly reduced gamma-secretase cleavage of betaAPP.

Presenilin 1-null mice die at birth from brain and skeletal developmental deformities due to disrupted Notch signaling. Presenilin 1-null mice also have severely reduced gamma-secretase cleavage of betaAPP. The assumption has been that facilitation of Notch signaling and betaAPP processing by presenilin 1 are analogous functions. Here we describe a presenilin 1-targetted mouse model that expresses extremely low levels ( approximately 1% of normal) of mutant PS1-M146L. Homozygous mice have significantly reduced viability due to a Notch-like phenotype. The animals that survive have severe axial skeletal deformities and markedly diminished gamma-secretase activity and accumulation of betaAPP-C100, but no obvious abnormalities in brain development. These results suggest that, in mice, a marked reduction of PS1-facilitated gamma-secretase activity is not detrimental to normal brain development.

Proton MR spectroscopic characterization of differences in regional brain metabolic abnormalities in mitochondrial encephalomyopathies.

Localized brain proton MR spectra were acquired from patients with different mitochondrial encephalomyopathies (myoclonus epilepsy with ragged-red fibers [MERRF], Kearns-Sayre syndrome [KSS], and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes [MELAS]). The regional brain metabolic abnormalities in patients with these syndromes showed different features consistent with the distinct phenotypes. In MERRF, only one of four patients showed an increase in the lactate/creatine resonance intensity ratio (an index of impairment of oxidative metabolism) in spectra from central (supraventricular) or occipital brain volumes, and this was small. There were significant decreases in N-acetylaspartate/creatine (a measure of neuronal loss or dysfunction) in central cerebral volumes of demented patients and, more prominently, in occipital volumes. In the one patient in whom it was studied, the cerebellum also showed a decreased N-acetylaspartate/creatine. Spectra from two patients with KSS both showed large (four- to sevenfold) increases in lactate/creatine and large decreases in N-acetylaspartate/creatine in central brain volumes. Yet another pattern of regional metabolic abnormality was present in the MELAS syndrome, where proton spectroscopic imaging demonstrated focal localization of abnormally increased lactate/creatine and decreased N-acetylaspartate/creatine to the regions of the stroke-like lesions on conventional MR images. Serial studies emphasized that the regional metabolic abnormalities in MELAS are highly variable as the stroke-like lesions appear and evolve.

Further studies of hippocampal representation during odor discrimination learning.

The contribution of hippocampal and nonhippocampal memory processing to simultaneous-cue odor discrimination learning was assessed. In this task, rats with hippocampal system damage consequent to fornix lesions (fornix rats) were severely and persistently impaired in discrimination learning, acquisition of learning set, and concurrent discrimination, although they occasionally solved some problems at a normal rate. By using those problems on which fornix rats succeeded, to permit comparisons of performance strategies with normal rats, differences between groups were shown on response latency measures and on probe trials involving the novel pairing of familiar odors. Normal rats had a bimodal distribution of response latencies, and their latency depended on where the S+ was presented. Fornix rats had short response latencies and responded equally quickly wherever the S+ was presented. Furthermore, when the representation of familiar S+ and S- odor pairs was challenged in probe trials, normal rats responded appropriately to the correct stimulus, whereas fornix rats behaved as if presented with a new odor pair. These data provide support for the view that the hippocampus participates in the representation of relations among odor (and other) stimuli and among other experiences and that it permits the flexible use of these representations in new contexts. In contrast, memory processing outside the hippocampal system can represent only the significance of individual stimuli and can be revealed only in a repetition of the original learning event.

Hippocampal system dysfunction and odor discrimination learning in rats: impairment or facilitation depending on representational demands.

The performance of normal rats and that of rats with hippocampal system damage were compared on acquisition of different versions of the same two-odor discrimination task that placed different encoding and representational demands on memory. Rats with fornix lesions were impaired when explicit comparisons among multiple odor cues and differential response choices were encouraged. However, when odor-cue comparison was hindered and explicit cues for response choice were eliminated, rats with fornix lesions out performed normal animals. The results support an hypothesis that the hippocampal system is critical to a memory representation based on encoding relations among multiple percepts, and other brain systems support performance adaptations based on encodings of stimuli individually.

Glomerular filtration rate in Indian non-insulin-dependent diabetics at various stages of albuminuria.

Sixty-seven non-insulin-dependent diabetic subjects were selected to estimate the glomerular filtration rate (GFR). All patients had satisfactory glycaemic control (HbA1 < 9.5%). GFR was determined using Technetium 99m DTPA by the method devised by Gates. Thirty-eight subjects had normal albumin excretion (UAE < 20 micrograms/min), 15 had UAE in the microalbuminuric range (20-100 micrograms/min), and the rest were macroalbuminuric (> 200 micrograms/min). GFR was lower in the normoalbuminuric patients as compared to the controls, but the decrease was not significant (71.5 (21.4) vs. 98.3 (16.1) ml/min per 1.73 m2. GFR was significantly decreased in both micro and macroalbuminuric groups (64.0 (24.5) and 53.8 (27.3) ml/min per 1.73 m2, respectively) (P < 0.05). No appreciable change in GFR was observed in normoalbuminuric patients with increasing duration of diabetes, however, there was a steady decline in GFR with time in both micro- and macroalbuminuric patients. Hypertension was present in 79%, 47% and 16% of macro-, micro- and normoalbuminuric patients, respectively. GFR was significantly lower in hypertensive diabetic patients compared to normotensives (52.3 vs. 76.1 ml/min per 1.73 m2) (P < 0.01), while this difference was not significant in the micro- and macroalbuminuric groups. We conclude from our study that the stage of hyperfiltration could not be detected in non-insulin-dependent diabetes and that hypertension has a significant influence on the rate of decline of GFR.

Collagen fiber organization is related to mechanical properties and remodeling in equine bone. A comparison of two methods.

We studied birefringence as an indicator of collagen fiber orientation in the diaphysis of the equine third metacarpal bone. We had previously shown that tissue from the lateral cortex of this bone is stronger monotonically, but less fatigue resistant, than tissue from the medial and dorsal regions. To learn whether collagen fiber orientation might play a role in this regional specialization, we tested three hypotheses using the same specimens: (1) collagen fiber orientation is regionally dependent; (2) remodeling changes collagen fiber orientation; (3) longitudinal collagen fibers correlate positively with modulus and monotonic bending strength and negatively with flexural fatigue life. Beams (N = 36) cut parallel to the long axes of six pairs of bones had been tested to determine elastic modulus (N = 36), and fatigue life (N= 24) or monotonic strength (N = 12) in four-point bending. Subsequently, histologic cross-sections were prepared, and porosity, active remodeling and past remodeling were quantified. Birefringence was measured as an indicator of transverse collagen orientation using plane-polarized light (PPL), and again using circularly polarized light (CPL). The CPL measurement was less variable than the PPL measurement. Both birefringence measures indicated that collagen was more longitudinally oriented in the lateral cortex than in the other two cortices. Longitudinally disposed collagen correlated with greater modulus and monotonic strength, but did not correlate with fatigue life. Remodeling was associated with more transverse collagen. Neither measure of birefringence was significantly correlated with porosity. It was concluded that, in the equine cannon bone, longitudinal collage fiber orientation is regionally variable, contributes to increased modulus and strength but not fatigue life, and is reduced by osteonal remodeling.

Wernicke and Alzheimer on the language disturbances of dementia and aphasia.

Signs of language dysfunction in dementia of the Alzheimer's type (DAT) and in the aphasic syndromes of transcortical sensory aphasia and Wernicke's aphasia are superficially similar. The unresolved question concerning the extent to which the language disturbances of DAT are "aphasic" is linked to a more fundamental question concerning the relation of language to thought, given that aphasia is often defined as language disturbance without disturbance of intellect, and dementia as dissolution of intellectual function, of which language forms an integral part. In this paper we explore the historical roots of today's debate by analyzing the original case studies of Wernicke (1874) and Alzheimer (1907, 1911). Although each of these neurologists described similar patterns of language disturbance, they drew different conclusions. Wernicke argued for a distinction between language and thought and between the language disturbances of aphasia and those of dementia. Alzheimer continued the then dominant paradigm of aphasia in describing the language disturbances of his demented patients as aphasic. Paradoxically his conclusion makes him appear, in contrast to Wernicke, to argue for the identity of the language disturbances of aphasia and dementia. Yet he himself acknowledged that the presence of focal language symptoms arising from diffuse degenerative pathology was indeed problematic. We conclude that today's discussion could profitably be refocused on the question which emerges from the original works of Wernicke and Alzheimer, which Alzheimer himself asked, and which remains unanswered: How can diffuse cerebral pathology give rise to a pattern of language deficit virtually identical to that of a focal lesion?

The phonology-morphosyntax interface: affixed words in agrammatism.

In three experiments with nondysarthric agrammatics, we explored the association between phonology and morphosyntax. (1) Contrasting phonological and nonphonological factors on inflectional-affix production of English verbs across three tasks in eight agrammatics, longer stem-syllabic length and stem-final-CC status resulted in poorer affix-production. (2) Studying verb inflections in six agrammatic Spanish-speakers, affix-length and affix-stress correlated with poorer repetition, as did low affix frequency. (3) Four English-speaking agrammatics read aloud and repeated derived words varying in syllable-length and stem-stress reassignment; both contributed independently to word-production difficulty. Phonological complexity of affixes and stems appears to reduce resources for morphological processing in nondysarthric agrammatics.

Compartment syndrome of the well leg as a result of the hemilithotomy position: a report of two cases and review of literature.

Compartment syndrome in the well leg as a complication of prolonged positioning in a hemilithotomy position is a serious complication that is rarely reported in the orthopaedic literature. A similar entity has been well described in urologic, gynecologic, and general surgery literature but, to the authors' knowledge, has been reported in only seven patients in the orthopaedic literature. The authors report two cases of unilateral compartment syndrome in a well leg during femoral nailing of the contralateral leg. Risk factors, theories of pathogenesis, and preventive measures are identified and discussed.

Relieving the agony of the new pain management standards.

The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has issued new standards for pain assessment in accredited hospitals and other health care settings, including hospice and home care. Under the new pain management standards, health care facilities will be called upon to recognize the right of patients to appropriate assessment and management of pain; to assess the existence of pain, its nature, and intensity; to record the results of the assessment in a way that facilitates regular reassessment and follow-up; to determine and ensure staff competency in pain assessment and management, and to address pain assessment and management in the orientation of all new staff; to establish policies and procedures that support the appropriate prescription or ordering of effective pain medications; to educate patients and their families about effective pain management; and to address patient needs for symptom management in the discharge planning process. Many health care organizations are reporting confusion and lack of understanding about the scope of the new standards. To address this issue, this article summarizes the new pain management standards. This article is based on a three-part series published in the Journal of Healthcare Safety, Compliance & Infection Control (January, March, and April 2000).

Co-oximetry.

The adequacy of tissue oxygenation depends on the interaction of many factors. Assuming the presence of sufficient tissue perfusion, oxygenation failure must be caused by depressed respiratory efficiency (shunt or other ventilation/perfusion mismatch), inadequate FIO2/PaO2 relationships (alveolar-capillary diffusion deficits, for example), or oxygen transport difficulties (hemoglobin loading/unloading dysfunction). When presented with patients whose respiratory distress is not alleviated by application of increasing levels of FIO2 and seemingly adequate SaO2 values, one must look toward less obvious reasons for the disparity between subjective and objective findings. Early response by clinicians to situations such as those just mentioned should include a survey and analysis of hemoglobin status. It is important to note that meaningful co-oximetry results depend on the quality of the patient history and other laboratory tests to rule out factors that might affect the co-oximetry results. Good preparation of the sample is essential to ensure that adequate hemolysis has occurred and that the sample was not contaminated prior to analysis. A well designed and executed program of preventive maintenance and QA is important. It should include preparation and sampling as well as technique and instrument integrity. All of these are essential for safe, effective, and accurate determination and dissemination of this important clinical information.

Mycobacterium fortuitum endocarditis and meningitis after balloon mitral valvotomy.

Mycobacteria rarely cause endocardial infections. We describe the clinical course of a patient who developed endocarditis, and meningitis with Mycobacterium fortuitum following balloon mitral valvotomy. The patient was treated with amikacin and clarithromycin but did not respond. She developed haemolytic anaemia as the terminal event.

Reducing the risks of ventilator-associated infections.

Mechanically ventilated patients are at high risk for developing nosocomial pneumonia. This article reviews the pathogenesis of ventilator-associated infections and ways nurses can intervene to reduce the risks to patients and to themselves.