Dermatology opinions via intranet could reduce waiting times.
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Diagnosis, Computer-Assisted↗
Biomedical subjects
D Shah
Publications and source records attributed to D Shah.
High-density mapping of activation through an incomplete isthmus ablation line.
BACKGROUND: Activation mechanisms through gaps in ablation lines and resulting electrograms are poorly understood. METHODS AND RESULTS: Eight patients (all men; age, 59+/-9 years) were studied during a recurrence of typical atrial flutter (cycle length, 233+/-19 ms) after a previous catheter ablation in the cavotricuspid isthmus. High-density 3-dimensional mapping of the isthmus was performed with the Cordis-Biosense EP Navigation system, and local conduction velocity (CV) was estimated. Maps created with 96+/-19 points revealed 0.8+/-0.3-cm gaps of recovered conduction in the ablation line. A broad wave front entered the lateral isthmus with a CV of 1.8+/-0.7 m/s, halted on the lesion line, and penetrated slowly through the gap with a CV of 0.3+/-0.1 m/s. Activation then curved and returned antidromically to activate the downstream flank of the line with a CV of 1.1+/-0.7 m/s. This front fused downstream of the line with slow transverse activation (CV, 0.4+/-0.3 m/s) parallel to it. The ablation line was demarcated by an incomplete line of convergent double potentials with isoelectric intervals (from 123+/-34 to 62+/-16 ms); each potential corresponded to local activation upstream and downstream of the lesions, while the intervening delay was produced by slow conduction through the gap combined with the progressively longer curved pathway of downstream antidromic activation as a function of distance from the gap. CONCLUSIONS: High-density isthmus mapping during recurrent flutter indicates slow conduction through gaps of recovered conduction of varying dimensions in the ablation line followed by a curved front of activation antidromically activating its downstream flank, this detour producing wide double potentials on the line.
Atrial Flutter↗
Involvement of lipid mediators on cytokine signaling and induction of secretory phospholipase A2 in immortalized astrocytes (DITNC).
Our previous studies demonstrated the ability of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin 1beta (IL-1beta), to stimulate NFkappaB/DNA binding and synthesis of secretory phospholipase A2 (sPLA2) in immortalized astrocytes (DITNC). In this study, we examined possible involvement of lipid mediators in the cytokine action. Using [14C]serine to label sphingomyelin and ceramide in these cells, subsequent exposure of cells to cytokines did not result in alteration of sphingomyelin/ceramide ratio. Furthermore, neither exogenous sphingomyelinase nor cell-permeable ceramides could stimulate NFkappaB/DNA binding. On the other hand, C-2 ceramide (0.3 microM) as well as other lipid mediators, such as lysophosphatidylcholine and arachidonic acid, were able to elicit a small increase in sPLA2 and potentiate the induction of sPLA2 by TNF-alpha. When DITNC cells were prelabeled with [32P]Pi, an increase in labeled phosphatidic acid (PA) was observed on treatment of cells with IL-1beta (200 U/mL). However, despite the ability of phorbol myristate acetate (PMA) to stimulate phospholipase D (PLD) and synthesis of phosphatidylethanol (PEt) in these cells, PLD activity was not affected by IL-1beta. With the [32P]labeled cells, however, PA-phosphohydrolase inhibitors, such as chlorpromazine and propranolol, could elicit large increases in labeled PA, indicating active PA metabolism in these cells. Cytokines also caused an increase in levels of diacylglycerol (DG) in these cells, although the source of this lipid pool is presently not understood. Taken together, these results provide evidence for the participation of PA and DG in cytokine signaling activity. Furthermore, although cytokines did not cause the release of ceramide, lipid mediators, such as lysophospholipids, and AA could modulate cytokine-mediated induction of sPLA2 in astrocytes.
Animals↗
Poly(beta-hydroxybutyrate) production in oilseed leukoplasts of brassica napus
Polyhydroxyalkanoates (PHAs) comprise a class of biodegradable polymers which offer an environmentally sustainable alternative to petroleum-based plastics. Production of PHAs in plants is attractive since current fermentation technology is prohibitively expensive. The PHA homopolymer poly(beta-hydroxybutyrate) (PHB) has previously been produced in leaves of Arabidopsis thaliana (Nawrath et al., 1994, Proc Natl Acad Sci USA 91: 12760-12764). However, Brassica napus oilseed may provide a better system for PHB production because acetyl-CoA, the substrate required in the first step of PHB biosynthesis, is prevalent during fatty acid biosynthesis. Three enzymatic activities are needed to synthesize PHB: a beta-ketothiolase, an acetoacetyl-CoA reductase and a PHB synthase. Genes from the bacterium Ralstonia eutropha encoding these enzymes were independently engineered behind the seed-specific Lesquerella fendleri oleate 12-hydroxylase promoter in a modular fashion. The gene cassettes were sequentially transferred into a single, multi-gene vector which was used to transform B. napus. Poly(beta-hydroxybutyrate) accumulated in leukoplasts to levels as high as 7.7% fresh seed weight of mature seeds. Electron-microscopy analyses indicated that leukoplasts from these plants were distorted, yet intact, and appeared to expand in response to polymer accumulation.
Journal Article↗
Radiofrequency catheter ablation of drug refractory symptomatic ventricular ectopy: short- and long-term results.
We performed radiofrequency catheter ablation (RFCA) in 12 consecutive patients (17-77 years) with daily, symptomatic, monomorphic ventricular ectopy (VE) (12,096 +/- 3,326 on 24-hour Holter) resistant to antiarrhythmic drugs. Nine patients had no apparent structural heart disease, 1 patient had a mild dilated cardiomyopathy, 1 patient had a treated mitral stenosis, and 1 patient had arrhythmogenic ventricular dysplasia. VE morphology was LBBB with inferior axis in 9 patients, RBBB with inferior axis in 2 patients, RBBB with superior axis in 1 patient. None of the patients had spontaneous or inducible sustained ventricular tachycardia. The VE focus was targeted with RF energy at the earliest endocardial activation site and based on a matching 12-lead ECG pace map. The VE focus was localized in the right outflow tract in 9 patients and on the left ventricle in 3 patients. RFCA was delivered with a standard 4-mm tip electrode. The ablation was initially successful in 11 patients and unsuccessful in 1 patient. All successfully ablated patients were asymptomatic and discharged without antiarrhythmic drugs. During follow-up (25 +/- 8; 17-38 months), two patients had a recurrence of symptoms, which were controlled by a previously ineffective drug. At the end of follow-up, 1,329 +/- 3198 VE were observed on Holter monitoring (P < 0.001 compared with initial values). No short- and long-term complications were observed. RFCA is a safe and effective method for treating drug-resistant symptomatic monomorphic VE in carefully selected patients. A persistent benefit without complications was obtained over a 2-year follow-up.
Adolescent↗
Red cell distribution and the recruitment of pulmonary diffusing capacity.
The distribution of red blood cells in alveolar capillaries is typically nonuniform, as shown by intravital microscopy and in alveolar tissue fixed in situ. To determine the effects of red cell distribution on pulmonary diffusive gas transport, we computed the uptake of CO across a two-dimensional geometric capillary model containing a variable number of red blood cells. Red blood cells are spaced uniformly, randomly, or clustered without overlap within the capillary. Total CO diffusing capacity (DLCO) and membrane diffusing capacity (DmCO) are calculated by a finite-element method. Results show that distribution of red blood cells at a fixed hematocrit greatly affects capillary CO uptake. At any given average capillary red cell density, the uniform distribution of red blood cells yields the highest DmCO and DLCO, whereas the clustered distribution yields the lowest values. Random nonuniform distribution of red blood cells within a single capillary segment reduces diffusive CO uptake by up to 30%. Nonuniform distribution of red blood cells among separate capillary segments can reduce diffusive CO uptake by >50%. This analysis demonstrates that pulmonary microvascular recruitment for gas exchange does not depend solely on the number of patent capillaries or the hematocrit; simple redistribution of red blood cells within capillaries can potentially account for 50% of the observed physiological recruitment of DLCO from rest to exercise.
Capillaries↗
Reproductive and sexual health and safe motherhood in the developing world.
The aim of this paper is to discuss the main hurdles and possible solutions concerning reproductive and sexual health and safe motherhood in the developing countries. In response to the changing global situation, a broader new concept of reproductive health has emerged. The Programme of Action of The International Conference on Population and Development (ICPD) emphasizes and highlights various aspects of reproductive health. No population in the world has met the goals of the ICPD. The problems are particularly acute in developing countries: between 20 and 40% of births are unwanted or wrongly timed, posing hardships for families and jeopardizing the health of a million women and children. An estimated 50 million induced abortions are performed each year, with some 20 million of these performed under unsafe conditions or by untrained providers. Almost 600,000 women die every year due to pregnancy-related causes, 99% of them in developing countries. Approximately 7.6 million infant deaths occur during the perinatal period each year. There are more than 333 million new cases of curable sexually transmitted diseases world-wide each year. Nearly 22 million people are estimated to be infected with the human immunodeficiency virus, of whom 14 million are in sub-Saharan Africa, with rapidly increasing numbers of infected persons in South and South-East Asia. When compared to the developed world, these figures are staggering because of barriers operating at different levels and preventing women from receiving care that is timely and of good quality. United efforts of obstetricians, pediatricians, sociologists, and different governmental and non-governmental organizations are required to achieve our targets.
Adolescent↗
Evaluation of the WHO/UNICEF algorithm for integrated management of childhood illness between the age of two months to five years.
OBJECTIVE: To evaluate the utility of the "WHO/UNICEF algorithm for integrated management of childhood illness (IMCI) between the age of 2 months to 5 years. DESIGN: Prospective observational. SETTING: The Outpatient Department and Emergency Room of a medical college hospital. METHODS: 203 children presenting to Outpatient Department (n=101) or Emergency Room (n=102) were assessed and classified as per 'IMCI' algorithm and treatment required was identified. A detailed evaluation with all relevant investigations was also done for these subjects. The final diagnoses made and therapies instituted on this basis served as 'gold standard'. The diagnostic and therapeutic agreements between the 'gold standard' and the IMCI and vertical (on the basis of primary presenting complaint) algorithms were computed. RESULTS: More than one illness was present in 135 (66.5%) of subjects as per 'gold standard'. The mean (SD) numbers of morbidities as per the gold standard and IMCI- low and high malaria risks were 2.1 (1.1), 1.8 (1.0) and 2.2 (1.1), respectively. Subjects having any referral criteria as per IMCI module had a greater co-existence of illnesses (mean 2.6 vs. 1.6 illnesses per child, respectively). The referral criteria proved useful in predicting hospitalization and a combination of hospitalization and observation; their sensitivity and specificity were 81% and 69% and 74% and 85%, respectively. IMCI algorithms covered majority (92%) of the recorded illnesses. A total agreement with IMCI (malaria low risk) was found in 129 (64%) cases while in 43 (22%) cases, there was partial agreement. Corresponding figures for vertical (split IMCI) program were 93 (46%; p<0.001) and 41 (25%). The difference was primarily due to underdiagnoses (30%). Diagnostic discordance of IMCI algorithm and gold standard was evident for the cough category due to underdiagnosis of bronchial asthma and bronchiolitis and an overdiagnosis of pneumonia whereas the discordance for fever was due to an overdiagnosis of malaria. Identical results were found for broad treatment categories. The IMCI algorithm had a provision for preventive services of immunization (16.3% possibility of availing missed opportunities) and feeding advice. CONCLUSIONS: There is a sound scientific basis for adopting the IMCI approach since: (i) co-existence of morbidities is frequent; (ii) severe illness is assessed with good sensitivity and specificity; and (iii) the IMCI algorithm is diagnostically and therapeutically superior to the vertical disease specific algorithms. The generic IMCI algorithm needs adaptation to reflect the regional morbidity profile.
Child Health Services↗
Current trends in management of the beta thalassemias.
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Blood Transfusion↗
Quantitative and qualitative analysis of DNA methylation at N3-adenine by N-methyl-N-nitrosourea.
The sequence-specific alkylation of DNA by N-methyl-N-nitrosourea (MNU) has been demonstrated for the minor groove N3-methyladenine (N3-MeAde) adduct using neutral thermal hydrolysis and polyacrylamide sequencing gels. The ratio of relative yields of N7- and N3-MeAde and N7-methylguanine (N7-MeGua) is approximately 0.03:0. 15:1.00, respectively, on the basis of the gel data, and these values are comparable to relative yields determined by bulk digestion of MNU-methylated DNA when HPLC was used to analyze the individual adducts. In contrast to the methylation at N7-guanine (N7-Gua) by MNU, alkylation at Ade shows minimal sequence selectivity. Similar to the methylation at N7-Gua, formation of N3-MeAde by MNU is inhibited by 50-200 mM concentrations of NaCl and DNA binding cations, including distamycin and spermine. However, N3-MeAde formation at Ade residues within methidiumpropyl-EDTA-Fe(II) footprinted distamycin DNA affinity binding regions is selectively inhibited at low concentrations of distamycin relative to Ade sites outside of ligand binding regions, and N7-Gua within or outside the distamycin binding regions. HPLC analysis shows that distamycin also quantitatively inhibits the production of N3-methylguanine when calf thymus DNA is treated with MNU or methyl methanesulfonate. The specific inhibitory effect of distamycin, which binds in the minor groove at Ade/Thy-rich sequences, provides additional evidence that the predominant DNA lesion detected at Ade by sequencing gel analysis involves minor groove N3-MeAde modifications.
Adenine↗
Permeation of unfolded basic fibroblast growth factor (bFGF) across rabbit buccal mucosa--does unfolding of bFGF enhance transport?
PURPOSE: To investigate whether recombinant human basic fibroblast growth factor (rhbFGF) would permeate freshly-excised rabbit buccal mucosa. In addition, the effect of a permeation enhancer (Na+ glycocholate) and the possibility of reversibly unfolding the globular protein to a more linear conformation to increase the permeability of the test protein was evaluated. METHODS: The in vitro flux of bFGF through freshly-excised rabbit buccal mucosa was determined using side-by-side diffusion systems. Detection of bFGF was performed using gradient elution, reversed-phase high-pressure liquid chromatography (RP-HPLC). Fluorescence spectroscopy and heparin affinity chromatography were used to assess the tertiary structure of bFGF. RESULTS: Preliminary in vitro results have demonstrated that the bFGF flux increased from 1.4 +/- 0.13 ng min-1 cm-2 to 3.2 +/- 0.38 ng min-1 cm-2 with the addition of 15 mM Na+ glycocholate (NaG) to the donor solution. Subsequent addition of guanidine HCl (GnHCl) to the donor solution (3 M) was not followed by a further increase in the flux of bFGF (2.9 +/- 0.26 ng min-1 cm-2). However, when the order of addition of the additives was reversed (GnHCl first followed by NaG), the flux of bFGF across rabbit buccal mucosa was increased. Upon addition of GnHCl, there was a significant (p < .05) increase in bFGF flux from 1.2 +/- 0.15 ng min-1 cm-2 to 5.0 +/- 0.58 ng min-1 cm-2. Addition of NaG further increased the flux to 8.5 +/- 1.1 ng min-1 cm-2 which was approximately 3- to 3.5-fold greater than that determined with the protein alone in the absence of any donor phase additives. The percent of parent bFGF remaining following a 3-hr exposure of a bFGF solution to either the mucosal, serosal, or both sides of rabbit buccal mucosa were 54.3 +/- 5.7%, 71.8 +/- 6.3%, and 36.2 +/- 5.4%, respectively with the majority of parent bFGF lost during the first 15 minutes. A model endopeptidase (endoproteinase Arg-C from mouse submaxillary gland) was shown in vitro to contribute to the loss in parent bFGF. CONCLUSIONS: The permeation of bFGF across rabbit buccal mucosa may be significantly increased by initially unfolding the protein with GnHCl and then treating the tissue with the permeation enhancer, NaG. Refolding and possible reactivation of bFGF's bioactivity may occur following membrane transport and subsequent dilution into an infinite sink.
Animals↗
Carotid endarterectomy surgery and ICU admissions: a regional anesthesia perspective.
Stroke is a major cause of mortality and morbidity in the United States. This study was performed to determine whether the authors' practice of monitoring the majority of patients in the postanesthesia care unit for 2 hours, selectively admitting the recovering carotid endarterectomy patients to the intensive care unit when feasible, and using regional anesthesia for the majority of cases, resulted in adverse outcomes or compromised the safety of the operation at a tertiary care academic medical center. The records of 337 patients (a total of 420 procedures) who underwent carotid endatertectomy surgery without concurrent heart surgery during a consecutive 18-month period ending in June, 1995 were reviewed. Regional anesthesia was the technique used in 97% of the procedures. Shunt placement was deemed necessary in 7% of the procedures. Postoperative strokes occurred in approximately 1% of patients. No shunted patients had a postoperative stroke. The rate of admission to intensive care units was 4%. Blood pressure control accounted for 73% of the patients admitted to intensive care units. Most patients required 2 hours of monitoring in the postanesthesia care unit before triage to the appropriate level of postoperative care. These results suggest that a monitoring period of 2 hours in the postanesthesia care unit allows for safe assessment of the postoperative carotid endarterectomy patient, and that routine intensive care unit admission after carotid endarterectomy surgery is not necessary.
Adult↗
Relationship between provider volume and mortality for carotid endarterectomies in New York state.
BACKGROUND AND PURPOSE: The objective of this study was to assess the relationship between each of 2 provider volume measures for carotid endarterectomies (CEs) (annual hospital volume and annual surgeon volume) and in-hospital mortality. New York's Statewide Planning and Research (SPARCS) administrative database was used to identify all 28 207 patients for whom carotid endarterectomy was the principal procedure performed in New York State hospitals between January 1, 1990, and December 31, 1995. METHODS: A statistical model was developed to predict in-hospital mortality using age, admission status, and several conditions found to be associated with higher-than-average mortality. This model was then used to calculate risk-adjusted mortality rates for various intersections of hospital and surgeon volume ranges. RESULTS: Risk-adjusted in-hospital mortality ranged from 1.96% (95% confidence interval, 1.47 to 2.57) for patients having surgeons with annual CE volumes of <5 in hospitals with annual CE volumes of </=100 to 0.94% (95% confidence interval, 0.73 to 1.19) for patients having surgeons with annual volumes of >/=5 in hospitals with annual CE volumes of >100. These 2 rates were statistically different. CONCLUSIONS: We conclude that the in-hospital mortality rates for carotid endarterectomies performed by surgeons with extremely low annual volumes (<5) and for hospitals with low volumes (</=100) are significantly higher than the in-hospital rates of higher-volume surgeons and hospitals, even after taking preprocedural patient severity of illness into account.
Adult↗
Bilateral microphthalmia, esophageal atresia, and cryptorchidism: the anophthalmia-esophageal-genital syndrome.
We report on a male infant with bilateral microphthalmia, esophageal atresia, and cryptorchidism. To our knowledge only 4 cases with a similar combination of congenital abnormalities have been previously reported, and it is likely that this represents a distinct entity. We suggest the name "anophthalmia-esophageal-genital-syndrome."
Anophthalmos↗
Ludwig's angina: improved treatment.
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Adult↗
Sexual Risk Cognitions Questionnaire: a reliability and validity study.
The Sexual Risk Cognitions Questionnaire was designed to assess the type and frequency of cognitions associated with unsafe sex. It consists of 22 core items (SRCQ-22) with six subsections. Each subsection consists of 8-12 items designed for specific subgroups defined by gender, sexual orientation and HIV serostatus. Data on reliability and validity are presented based on a sample of 344 respondents in London. Reliability for all sections of the questionnaire was high but sample numbers were relatively small for some subsections. Validity for the SRCQ-22 was assessed in terms of its relationship with self-reported sexual behaviour among men who have sex with men who made up the largest proportion (70%) of the sample. The results indicate that the SRCQ-22 is a reliable measure for assessing cognitions related to HIV risk sexual behaviour in this population and supports the view that they are important determinants of safe and unsafe behaviour.
Adolescent↗
Nomenclature and characterization of transisthmus conduction after ablation of typical atrial flutter.
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Atrial Flutter↗