Splenic irradiation in end-stage cystic fibrosis.
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Biomedical subjects
Publications and source records attributed to A Mehta.
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The steady rise in caesarean section rates is an emerging area of concern in mother-child healthcare and a matter of international attention, since the trend is no longer confined to western industrialized countries. Crude and caesarean section-related perinatal mortality and case-fatality rates may well serve as public-health indicators. Monitoring time-trends in caesarean section rates has been considered a useful approach in the recognition of this rapidly-changing health policy and in estimating the magnitude of this problem. The study examined the observed time-trends in caesarean section rates in relation to perinatal mortality rates and maternal case-fatality rates in a hospital setting in Mumbai, India, using 1957-1998 data on retrospective cohort. Both overall rates and those specific to type of delivery were assessed. During 1957-1998, the caesarean section rates in the Nowrosjee Wadia Maternity Hospital (NWMH) increased from 1.9% to 16%, with the most significant rise over the past decade. The perinatal mortality rate showed a significant reduction from 69 per 1,000 in 1957 to 36 per 1,000 in 1992 and remained steady in the 1990s despite the higher caesarean section rates. The caesarean section rate in the NWMH rose by almost 10-fold during 1957-1998. No improvement in perinatal outcome was observed beyond a caesarean section rate of 10%, but the perinatal mortality rate in caesarean births increased significantly due to a more liberal use of caesarean sections in preterm deliveries and those that yielded low-birth-weight babies.
Knowledge of the prevalence of latent Mycobacterium tuberculosis infection is crucial for effective tuberculosis control, but tuberculin skin test surveys have major limitations, including poor specificity because of the broad antigenic cross-reactivity of tuberculin. The M. tuberculosis RD1 genomic segment encodes proteins, such as early secretory antigenic target (ESAT)-6, that are absent from M. bovis bacille Calmette-Guérin (BCG) and most environmental mycobacteria. We recently identified circulating ESAT-6-specific T cells as an accurate marker of M. tuberculosis infection. Here, interferon-gamma-secreting T cells specific for peptides derived from ESAT-6 and a second RD1 gene product, CFP10, were enumerated in 100 prospectively recruited healthy adults in Bombay (Mumbai), India. Eighty percent responded to >/=1 antigen, and many donors had high frequencies of T cells that were specific for certain immunodominant peptides. In contrast, of 40 mostly BCG-vaccinated, United Kingdom-resident healthy adults, none responded to either antigen. This study suggests an 80% prevalence of latent M. tuberculosis infection in urban India.
Although [Cl(-)](i) regulates many cellular functions including cell secretion, the mechanisms governing these actions are not known. We have previously shown that the apical membrane of airway epithelium contains a 37-kDa phosphoprotein (p37) whose phosphorylation is regulated by chloride concentration. Using metal affinity (chelating Fe(3+)-Sepharose) and anion exchange (POROS HQ 20) chromatography, we have purified p37 from ovine tracheal epithelia to electrophoretic homogeneity. Sequence analysis and immunoprecipitation using monoclonal and specific polyclonal antibodies identified p37 as annexin I, a member of a family of Ca(2+)-dependent phospholipid-binding proteins. Phosphate on [(32)P]annexin I, phosphorylated using both [gamma-(32)P]ATP and [gamma-(32)P]GTP, was labile under acidic but not alkaline conditions. Phosphoamino acid analysis showed the presence of phosphohistidine. The site of phosphorylation was localized to a carboxyl-terminal fragment of annexin I. Our data suggest that cAMP and AMP (but not cGMP) may regulate annexin I histidine phosphorylation. We propose a role for annexin I in an intracellular signaling system involving histidine phosphorylation.
Local infusions of the nonselective dopaminergic agonist apomorphine into the subthalamic nucleus of rats has been shown to elicit orofacial dyskinesia which can be blocked by D1 but not D2 receptor antagonists. In the present study, we show that the selective D1 agonist A77636 also induces orofacial dyskinesia when injected into the subthalamic nucleus of awake rats, thus confirming a role for D1 receptors in this effect. We also examined the dyskinesia induced by intrasubthalamic injections of apomorphine in rats with an ipsilateral lesion of the nigrostriatal pathway. The orofacial response to local administration of apomorphine (1.0 microg) into the subthalamic nucleus was markedly increased in the lesioned rats. As in control rats, the enhanced behavioral response seen in lesioned rats was blocked by peripheral administration of D1 antagonists. Although D1 receptor binding autoradiography revealed no difference in D1 receptor binding in the subthalamic nucleus on the side of the lesion compared to controls, D1 binding was higher in the subthalamic nucleus on the side of the lesion compared to the contralateral side. The increased behavioral response observed after unilateral dopamine denervation suggests that the subthalamic nucleus is tonically regulated by dopaminergic projections from the substantia nigra. Furthermore, the data suggest that subthalamic D1 receptors may be involved in the development of dyskinesia induced by dopaminergic drugs.
By forming a molecular tether between two membranes, p115, giantin, and GM130 may mediate multiple Golgi-related processes including vesicle transport, cisternae formation, and cisternal stacking. The tether is proposed to involve the simultaneous binding of p115 to giantin on one membrane and to GM130 on another membrane. To explore this model, we tested for the presence of the putative giantin-p115-GM130 ternary complex. We first mapped p115-binding site in giantin to a 70-amino acid coiled-coil domain at the extreme N terminus, a position that may exist up to 400 nm away from the Golgi membrane. We then generated glutathione S-transferase (GST) fusion proteins containing either giantin's or GM130's p115 binding site and tested whether such proteins could bind p115 and GM130 or bind p115 and giantin, respectively. Unexpectedly, GST fusions containing either the giantin or the GM130 p115 binding site efficiently bound p115, but the p115 bound to GST-giantin did not bind GM130, and the p115 bound to GST-GM130 did not bind giantin. To explain this result, we mapped the giantin binding site in p115 and found that it is located at the C-terminal acidic domain, the same domain involved in binding GM130. The presence of a single binding site in p115 for giantin and GM130 was confirmed by demonstration that giantin and GM130 compete for binding to p115. These results question a simple tethering model involving a ternary giantin-p115-GM130 complex and suggest that p115-giantin and p115-GM130 interactions might mediate independent membrane tethering events.
Oxalic acid is present as nutritional stress in many crop plants like Amaranth and Lathyrus. Oxalic acid has also been found to be involved in the attacking mechanism of several phytopathogenic fungi. A full-length cDNA for oxalate decarboxylase, an oxalate-catabolizing enzyme, was isolated by using 5'-rapid amplification of cDNA ends-polymerase chain reaction of a partial cDNA as cloned earlier from our laboratory (Mehta, A., and Datta, A. (1991) J. Biol. Chem. 266, 23548-23553). By screening a genomic library from Collybia velutipes with this cDNA as a probe, a genomic clone has been isolated. Sequence analyses and comparison of the genomic sequence with the cDNA sequence revealed that the cDNA is interrupted with 17 small introns. The cDNA has been successfully expressed in cytosol and vacuole of transgenic tobacco and tomato plants. The transgenic plants show normal phenotype, and the transferred trait is stably inherited to the next generation. The recombinant enzyme is partially glycosylated and shows oxalate decarboxylase activity in vitro as well as in vivo. Transgenic tobacco and tomato plants expressing oxalate decarboxylase show remarkable resistance to phytopathogenic fungus Sclerotinia sclerotiorum that utilizes oxalic acid during infestation. The result presented in the paper represents a novel approach to develop transgenic plants resistant to fungal infection.
The objective of this study was to identify left atrial (LA) abnormality on the electrocardiogram and other related variables as predictors of left ventricular (LV) hypertrophy in the presence of left bundle branch block (LBBB). In the presence of complete LBBB, the diagnosis of electrocardiographic abnormalities is problematic and that of LV hypertrophy remains difficult. The usual electrocardiographic criteria applied for the diagnosis of LV hypertrophy may not be reliable in the presence of LBBB. Therefore, noninvasive criteria will help physicians diagnose LV hypertrophy with electrocardiography. LA abnormality on the electrocardiogram was assessed by 2 independent observers as predictor of LV hypertrophy in the presence of LBBB in 120 patients, and data were compared with those of 100 patients without LA abnormality. LV mass was calculated from echocardiographic data. Besides LA abnormality, the other variables studied for prediction of LV hypertrophy were gender, age, body surface area, body mass index, frontal axis, and QrS duration. Of the 6 criteria analyzed, the P terminal force was found to be the most common and consistent criterion to detect LA abnormality. LV hypertrophy was confirmed by echocardiographic determination of LV mass in both groups. Observers reliably differentiated between the hypertrophied and normal-sized left ventricle in the presence of LBBB by correlating LA abnormality with LV mass determined by echocardiography. Observer 1 detected LA abnormality in 89% and observer 2 in 84% of patients. False-positive results were present in 11% and 16%. The observer's recognition of LA abnormality in the present study was 91%. The 2 observers showed a sensitivity of 81% and 79% and a specificity of 91% and 88%, respectively, when diagnosis of LV hypertrophy was determined. LV mass increased significantly and was diagnostic of LV hypertrophy in 92% of patients with LA abnormality. In the remaining 11 patients (8%), the LA abnormality was of marginal abnormal magnitude. Each 0.01-mV/s increase in LA abnormality gave an increase of 30 g of LV mass. LV mass was increased in 86% of patients when corrected by body surface area. LV hypertrophy in the presence of LBBB on electrocardiography was found in only 13 patients (10%) when the 6 frequently used conventional criteria for diagnosis of LV hypertrophy by electrocardiography were used. Regression analysis revealed LA abnormality to be a strong independent predictor of increased LV mass. Multivariate analysis also revealed age, body mass index, body surface area, frontal axis, and QrS duration to be significant predictors of LV mass. This noninvasive study correlates LA abnormality by electrocardiogram and LV hypertrophy with echocardiography to conclude that LA abnormality was significantly diagnostic of LV hypertrophy in the presence of LBBB. Age, body mass index, body surface area, frontal axis, and QrS duration were also significant predictors of LV mass.
Radiology departments are beginning to embrace new technologies to decrease operating budgets and improve services. One of these technologies is the picture archiving and communication system (PACS). PACS, through immediate availability of images to the radiologist, promises to decrease turnaround times of reports to the clinician. The purpose of this study was to determine if this technology actually decreases the time for referring clinicians to receive reports generated by the radiologist. The time to provide a preliminary report by a resident and time to finalize this report by a board-certified radiologist was retrospectively obtained for 6,022 abdominal and pelvic computed tomography (CT) scans over two 1-year periods from March 1, 1997 to March 1, 1998 and from March 1, 1998 to March 1, 1999. During the first year, interpretation was conducted using hard-copy film and during the second using PACS. In both 1-year periods, MedSpeak voice recognition software (IBM, White Plains, NY) was employed for dictation. The average time for a preliminary report for a abdominal and pelvic CT, dictated by a resident or fellow, to be available in alphanumeric form on the hospital information system using hard-copy film was 3.73 days. The installation of a PACS system decreased this turnaround time to 0.56 days, representing an 85.0% improvement. The time to availability of final reports, ie, signed by board-certified staff radiologists, was 5.49 days in the hard-copy interpretation subset and 5.97 days in the PACS subset. The addition of PACS into an academic gastrointestinal radiology division improves availability of alphanumeric preliminary reports of abdominal and pelvic CTs on the hospital information system (HIS), dictated by a resident or fellow, by 85.0%. There was no impact with a PACS on the time to final sign reports by a staff board certified radiologist as signing patterns remained relatively constant over the two interpretation formats.
As radiology makes advances toward filmlessness, all of medicine is headed, just as rapidly, toward paperless transmission of patient information. While there are obvious advantages to this electronic approach, and several standards to conform to for the transmission of textual (Health Level 7 [HL-7]) and image (Digital Imaging and Communications in Medicine [DICOM]) data, it is the integration of these two data sets that is clinically essential and yet poorly defined. This report defines an approach for, and the successful implementation of, the integration of radiologic image data with textual data contained within the electronic patient record (EPR) through the use of standard internet protocols. Incorporation of medical images in the EPR has proven to be critical to the successful deployment of picture archiving and communications systems (PACS) and the reduction of film consumption at Massachusetts General Hospital (MGH). Since the installation of the first internet-based Image Data Repository (IDR) at MGH in 1995, the system has adequately served to meet the needs of clinical requests by both radiology-only browser users and users of the EPR. It has drastically reduced the need for film and provided concurrent display of images and text throughout the institution and beyond.
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Honeys from different floral sources were evaluated for their antioxidant content and for their ability to inhibit enzymatic browning in fruits and vegetables. Antioxidant contents of honeys vary widely from different floral sources, as do their abilities to protect against enzymatic browning. Polyphenol oxidase (PPO) activity was reduced over a range of approximately 2-45% in fruit and vegetable homogenates, corresponding to a reduction in browning index by 2.5-12 units. Soy honey was particularly effective when compared to clover honey, which had a similar antioxidant content. When compared to commercial inhibitors of browning, honeys were less effective; however, in combination they added to the effectiveness of metabisulfite and ascorbic acid. Honey has great potential to be used as a natural source of antioxidants to reduce the negative effects of PPO browning in fruit and vegetable processing.
In 1996, we prospectively audited peri-operative transfusion practice in elective surgical patients over a 3-month period. Two-unit transfusions represented 60% of all transfusions. Haemoglobin was measured infrequently prior to transfusion and the main 'trigger' for transfusion was an estimated blood loss in excess of 500 ml. Transfusion guidelines that required the haemoglobin level to be measured immediately before transfusion were introduced. The audit was repeated in 1998; transfusion 'triggers' and the number of transfusions for the two periods were compared. In the second audit, the total number of transfusions decreased by 43%. The mean estimated blood loss associated with a 2-unit transfusion had increased from 608 (373) ml to 1320 (644) ml (p < 0.01) and the estimated haemoglobin concentration after transfusion had decreased from 12.4 (1.8) g.dl-1 to 9.9 (2.4) g.dl-1 (p < 0.01). These results suggest that transfusion guidelines can have a significant impact on clinical practice.
Glucose-6-phosphate dehydrogenase (G6PD) is expressed in all tissues, where it catalyses the first step in the pentose phosphate pathway. G6PD deficiency is prevalent throughout tropical and subtropical regions of the world because of the protection it affords during malaria infection. Although most affected individuals are asymptomatic, there is a risk of neonatal jaundice and acute haemolytic anaemia, triggered by infection and the ingestion of certain drugs and broad beans (favism). A rare but more severe form of G6PD deficiency is found throughout the world and is associated with chronic non-spherocytic haemolytic anaemia. Many deficient variants of G6PD have been described. DNA sequence analysis has shown that the vast majority of these are caused by single amino acid substitutions. The three-dimensional structure of G6PD shows a classical dinucleotide binding domain and a novel beta + alpha domain involved in dimerization.
A 90-year-old woman presented with an accidental maxillofacial-clival penetrating injury with a butcher's knife, with its tip reaching the immediate proximity of the basilar artery. The knife was removed at surgery, with no untoward sequelae.
Cilia provide the driving force for mucociliary clearance, the process that removes mucus from the airways. Protein kinase C (PKC) plays a poorly understood regulatory role in phosphorylation-based signal transduction cascades, including the control of human mucociliary clearance, especially with respect to ciliary beat frequency (CBF). Ciliary studies minimize the importance of fluid flow, because it is generally accepted that flow increases CBF. Here, we studied postflow events by measuring CBF in vitro in volunteers. Rose chamber-loaded cells were pulsed for 5 minutes at 30 mL/h in medium-199 +/- PKC modulators at 20 degrees C. The 5-minute pulse precipitated a fall in CBF noted within 1 minute after flow (acute dip response [ADR] to 84 +/- 2% of preflow baseline). Thereafter, CBF rose to 8% below baseline for 30 minutes [postrecovery plateau at 92 +/- 3%]. Preincubation with 1 microM of phorbol 12-myristate 13-acetate (PMA), a PKC-activating phorbol ester attenuated the ADR (c. 95%) and restored the postrecovery plateau almost to baseline levels (98 +/- 0.7%; p > 0.10 compared with baseline CBF). With respect to the ADR, the PMA protective effect was lost in the presence of the selective PKC inhibitor myristoylated epidermal growth factor peptide 651d-658 (Myr-PKCI; 10 microM). Myr-PKCI alone changed the ADR pattern such that the CBF remained at 15% below preflow baseline. We conclude that CBF fall and recovery after a fluid pulse is regulated by PKC activity either directly or indirectly.
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We describe the surface properties of a simple lattice model of a sandpile that includes evolving structural disorder. We present a dynamical scaling hypothesis for generic sandpile automata and, additionally, explore the kinetic roughening of the sandpile surface, indicating its relationship with the sandpile evolution. Finally, we comment on the surprisingly good agreement found between this model, and a previous continuum model of sandpile dynamics, from the viewpoint of critical phenomena.