Comment on "Probabilistic quantum memories".
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Comment↗
Biomedical subjects
A Nayak
Publications and source records attributed to A Nayak.
The health-related quality of life effects of once-daily cetirizine HCl in patients with seasonal allergic rhinitis: a randomized double-blind, placebo-controlled trial.
BACKGROUND: Seasonal allergic rhinitis (SAR) is characterized by subjectively irritating symptoms that can have a substantial impact on the patient's health-related quality of life (HRQL), adversely affecting physical and social or work activity, interpersonal relationships, and general psychological well-being. The objective of this study was to test the effect of cetirizine HCl 10 mg once daily on the HRQL of adult patients 18-65 years of age with SAR, concurrently assessing safety and efficacy. METHODS: Randomized double-blind, placebo-controlled, parallel group trial conducted during the 1999 spring SAR season at 19 centers in the US. Following a 1-week placebo run-in period, qualified patients were randomized to cetirizine 10 mg, or placebo once daily for a 2-week treatment period. Change in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and Total Symptom Severity Complex (TSSC) scores from baseline were the primary outcomes of interest. RESULTS: Of the 611 patients enrolled, 403 (66%) were randomized. Cetirizine-treated patients reported significantly greater improvement in overall HRQL (P < 0.001) and in each of the seven domains of the RQLQ at all time-points (P < 0.05 to < 0.001) than the placebo group. They also experienced significantly greater symptom relief (P < 0.001) and were more satisfied with treatment (65% vs. 44%) compared to the placebo group. Correlations between symptomatic relief and overall HRQL improvement were moderate to strong and statistically significant (r = 0.49-0.68, P < 0.01). CONCLUSIONS: Results of this study are consistent with previous investigations, suggesting cetirizine HCl 10 mg taken once daily in the morning offers symptomatic relief that improves the HRQL of adults suffering from SAR.
Adolescent↗
Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial.
CONTEXT: Seasonal allergic rhinitis is a common IgE-mediated disorder that produces troublesome symptoms. A recombinant humanized monoclonal anti-IgE antibody (omalizumab) forms complexes with free IgE, blocking its interaction with mast cells and basophils and lowering free IgE levels in the circulation. OBJECTIVE: To assess the efficacy and safety of omalizumab for prophylaxis of symptoms in patients with seasonal allergic rhinitis. DESIGN: Randomized, double-blind, dose-ranging, placebo-controlled trial conducted from July 25 through November 21, 1997. SETTING: Twenty-five outpatient centers throughout the United States. PATIENTS: Five hundred thirty-six patients aged 12 to 75 years with at least a 2-year history of moderate to severe ragweed-induced seasonal allergic rhinitis and a baseline IgE level between 30 and 700 IU/mL. INTERVENTIONS: Patients were randomly assigned to receive omalizumab, 50 mg (n = 137), 150 mg (n = 134), or 300 mg (n = 129), or placebo (n = 136) subcutaneously just prior to ragweed season and repeated during the pollen season every 3 weeks in patients with baseline IgE levels of 151 to 700 IU/mL (4 total treatments) and every 4 weeks in patients with baseline IgE levels of 30 to 150 IU/mL (3 total treatments). MAIN OUTCOME MEASURES: Self-assessed daily nasal symptom severity scores (range, 0-3), rescue antihistamine use, and rhinitis-specific quality of life during the 12 weeks from the start of treatment. RESULTS: Nasal symptom severity scores were significantly lower in patients who received 300 mg of omalizumab than in those who received placebo (least squares means, 0.75 vs 0.98, respectively; P =.002). A significant association was observed between IgE reduction and nasal symptoms and rescue antihistamine use. Rhinitis-specific quality of life scores were consistently better in patients who received 300 mg of omalizumab than in those who received lower dosages or placebo and did not decline during peak season. The frequency of adverse events was not significantly different among the omalizumab and placebo groups. CONCLUSION: Omalizumab decreased serum free IgE levels and provided clinical benefit in a dose-dependent fashion in patients with seasonal allergic rhinitis.
Adolescent↗
Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab).
BACKGROUND AND OBJECTIVE: There seems to be a strong causal relationship between allergy and the origins of asthma. Susceptibility to both is determined by a combination of genetics and environment acting through a complex network of cytokines. Nearly 90% of affected children have positive skin tests indicating the presence of specific immunoglobulin E (IgE), with sensitivity to house dust mite, Alternaria, cockroach, cat, and dog most closely linked to the disease. Greater exposure to house dust mite during infancy leads to earlier onset of wheezing, and elevated serum IgE levels correlate with the appearance of asthma symptoms. Specific IgE binds to high-affinity (FcepsilonRI) receptors on mast cells and basophils. The IgE-mediated reactions that follow exposure of sensitized mast cells to an allergen are designated early- and late-phase asthmatic responses (EAR and LAR). EAR is characterized by release of histamine and other preformed mediators within 1 hour of allergen exposure. It is often followed by LAR, an infiltration of the airways by inflammatory cells associated with an episode of more prolonged, and usually more severe airflow obstruction, 4 to 8 hours after antigen exposure. Chronic airway symptoms result from persistent LAR caused by continuous allergen exposure. IgE antibodies are capable of passive transfer of both EAR and LAR sensitivity. IgE-mediated mast cell activation contributes to chronic tissue eosinophilia and airway remodeling, with permanent loss in pulmonary function. Omalizumab (rhuMAb-E25) is a recombinant, humanized, monoclonal anti-IgE antibody of mouse origin developed for the treatment of IgE-mediated diseases. Omalizumab binds to free IgE at the same site as the high-affinity receptor. Although it attaches to free IgE, it does not bind to IgA, IgG, or cell-bound IgE. It therefore does not induce cross-linking of cell-bound IgE, which would lead to the release of allergic mediators. It has been reported to decrease serum IgE levels in a dose-dependent manner, inhibit EAR and LAR, and cause a down-regulation of FcepsilonRI receptors on basophils. Omalizumab has been reported to be safe and effective in improving asthma control and reducing the requirement for oral and inhaled corticosteroids. This double-blind, randomized, placebo-controlled study evaluated the safety, steroid-sparing effects, and impact on disease exacerbations of omalizumab in the treatment of childhood asthma. Methods. Participants were 334 males and premenarchal females aged 6 to 12 years, with moderate to severe allergic asthma requiring treatment with inhaled corticosteroids. During a run-in phase, all children were switched to equivalent doses of beclomethasone dipropionate (BDP), and the dose was adjusted to assure maintenance of asthma control achieved with previous corticosteroid treatment. Children were randomized to subcutaneously administered placebo (N = 109) or omalizumab (N = 225) at a dose based on body weight and initial serum IgE (0.016 mg/kg/IgE [IU/mL] per 4 weeks). BDP dose (initial range 168-420 microg/d) was kept stable for 16 weeks (stable-steroid phase), reduced over 8 weeks to the minimum effective dose (steroid-reduction phase), and maintained constant for the final 4 weeks. RESULTS: More participants in the omalizumab group decreased their BDP dose, and their reduction was greater than that of the placebo group (median reduction 100% vs 66.7%). BDP was withdrawn completely in 55% of the omalizumab group versus 39% of the placebo group. The incidence and the frequency of asthma exacerbations requiring treatment with doubling of BDP dose or systemic corticosteroids were lower in the omalizumab group. The treatment differences were statistically significant during the steroid-reduction phase, during which fewer participants in the omalizumab group had asthma exacerbation episodes (18.2% vs 38.5%), and the mean number of episodes per patient was smaller than with placebo (0.42 vs 2.72). Five asthma exacerbations requiring hospitalization all occurred in the placebo group. Participants' and investigators' global evaluations of treatment effectiveness were more favorable for omalizumab than placebo. Investigators rated effectiveness excellent for 31.5% of the omalizumab group versus 16.3% of the placebo group and good for 44.7% of the omalizumab group versus 32.7% of the placebo group. There was little change in asthma symptom scores or spirometry measurements during either the stable-steroid or steroid dose-reduction phase, with minimal differences between the treatment groups. The requirement for rescue medication in the omalizumab group during both the stable-steroid and steroid dose-reduction phases was consistently lower than at baseline. At week 28, the median number of puffs of rescue medication taken daily was 0 in the omalizumab group and 0.46 in the placebo group. The change from baseline was significant in favor of omalizumab. (ABSTRACT TRUNCATED)
Acute Disease↗
Familial nephrotic syndrome: clinical spectrum and linkage to chromosome 19q13.
BACKGROUND: Familial nephrotic syndrome (NS) has both autosomal dominant and recessive forms of inheritance. Recent studies in families with an autosomal dominant form of focal segmental glomerulosclerosis (FSGS) have been at odds concerning linkage to chromosome 19q13 (Mathis et al, Kidney Int 53:282-286, 1998; Winn et al, Kidney Int 55:1241-1246, 1999), suggesting genetic heterogeneity. This study examines the clinical features and confirms linkage to chromosome 19q13 in a family with autosomal dominant NS. METHODS: DNA samples were obtained from 16 of 17 family members. Genomic DNA was isolated, and polymerase chain reaction was performed for five markers spanning the area of interest on chromosome 19q13. Data were evaluated using two- and six-point linkage analysis. RESULTS: Clinical features included presentation of NS in childhood, steroid unresponsiveness, and slow progression to renal failure. Renal biopsy in affected family members showed lesions ranging from minimal change to mesangial proliferative glomerulonephritis to FSGS. Linkage was confirmed between the disease state and chromosome 19q13, with a maximum logarithm of odds (LOD) score of 2.41. Linkage was observed for a 7 cM region on chromosome 19q13, defined by markers D19S425 and D19S220. CONCLUSIONS: This study confirms the Mathis et al report of linkage to chromosome 19q13 in a family with autosomal dominant NS. However, there were notable differences in the presenting clinical and histopathologic features of our affected family members compared with those of Mathis et al. This suggests that the gene on chromosome 19q13 may be responsible for considerable phenotypic heterogeneity and variable expression in both clinical presentation and renal histopathology.
Adolescent↗
Spatial codes and the hardness of string folding problems.
We present a general technique for proving NP-hardness (under randomized polynomial time reductions) of string folding problems over a finite alphabet. All previous such intractability results have required an unbounded alphabet size. These problems correspond to the protein folding problem in variants of the hydrophobic-hydrophilic (or HP) model with a fixed number of monomer types. Our proof also establishes the MAX SNP-hardness of these problems (again under randomized polynomial time reductions). This means that obtaining even an approximate solution to the protein folding problem, to within some fixed constant factor, is NP-hard. Our technique involves replacing the symbols of an unbounded alphabet by code-words over a fixed alphabet, and has two novel aspects. The first is the essential use of the approximation hardness of the source problem in the reduction, even for the proof of NP-hardness. The second is the concept of spatial codes, a variant of classical error-correcting codes in which different codewords are required to have large "distance" from one another even when they are arbitrarily embedded in three-dimensional space.
Computational Biology↗
GPs' perceptions of patient influence on prescribing.
BACKGROUND: Controlling prescribing costs is an issue of concern to many GPs. OBJECTIVE AND METHODS: This paper is based on interviews with 21 GPs in which they were asked about influences on prescribing budgets. RESULTS: The results presented relate specifically to GPs' perceptions of the influence of patients on prescribing. Perceptions of patient demand were described both in terms of a general demand and demand by patients with specific health beliefs or particular social characteristics. Generally, GPs reported that decisions to prescribe were informed by a concern to maintain a good relationship with their patients, and not to risk the relationship by not prescribing when they believed a prescription was expected. CONCLUSIONS: Although information was available about whether practices had a 'high' or 'low' budget, and whether they were under- or overspent, there did not appear to be any relationship between GPs' beliefs that patient expectations affected their prescribing and whether they were under or over budget. This paper suggests that patient demand for prescriptions may not only be overestimated but also perpetuated by GPs' belief in its existence and a wish to maintain a good doctor-patient relationship.
Attitude of Health Personnel↗
Depth of anesthesia estimation and control.
A fully automated system was developed for the depth of anesthesia estimation and control with the intravenous anesthetic, Propofol. The system determines the anesthesia depth by assessing the characteristics of the mid-latency auditory evoked potentials (MLAEP). The discrete time wavelet transformation was used for compacting the MLAEP which localizes the time and the frequency of the waveform. Feature reduction utilizing step discriminant analysis selected those wavelet coefficients which best distinguish the waveforms of those responders from the nonresponders. A total of four features chosen by such analysis coupled with the Propofol effect-site concentration were used to train a four-layer artificial neural network for classifying between the responders and the nonresponders. The Propofol is delivered by a mechanical syringe infusion pump controlled by Stanpump which also estimates the Propofol effect-site and plasma concentrations using a three-compartment pharmacokinetic model with the Tackley parameter set. In the animal experiments on dogs, the system achieved a 89.2% accuracy rate for classifying anesthesia depth. This result was further improved when running in real-time with a confidence level estimator which evaluates the reliability of each neural network output. The anesthesia level is adjusted by scheduled incrementation and a fuzzy-logic based controller which assesses the mean arterial pressure and/or the heart rate for decrementation as necessary. Various safety mechanisms are implemented to safeguard the patient from erratic controller actions caused by external disturbances. This system completed with a friendly interface has shown satisfactory performance in estimating and controlling the depth of anesthesia.
Algorithms↗
Presynaptic and postsynaptic mechanisms of long-term potentiation.
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Animals↗
Maintenance of late-phase LTP is accompanied by PKA-dependent increase in AMPA receptor synthesis.
Long-term potentiation (LTP) is a form of synaptic plasticity that has been extensively studied as a putative mechanism underlying learning and memory. A late phase of LTP occurring 3-5 hours after stimulation and depending on transcription, protein synthesis and cyclic-AMP-dependent protein kinase (protein kinase A, or PKA) has been described, but it is not known whether transcription of presynaptic and/or postsynaptic genes is required to support late-phase LTP. Here we show that late-phase LTP can be obtained in rat hippocampal CA1 mini-slices in which the cell bodies of presynaptic Schaffer collateral/commissural fibres are removed. Thus, transcription of presynaptic genes is not necessary to support maintenance of late-phase LTP. The AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate) receptor is the predominant mediator of the ionotropic response to synaptically released glutamate in the hippocampus and it has been implicated in LTP maintenance. We find that synthesis of AMPA receptor subunits is increased three hours after LTP induction: this effect on the synthesis of the AMPA receptor is blocked by inhibitors of PKA and of transcription. Our results support the idea of a postsynaptic mechanism maintaining late-phase LTP, in which AMPA receptor synthesis is increased as a result of PKA-dependent gene transcription.
Animals↗
Anesthesia control using midlatency auditory evoked potentials.
This paper shows the development of a system to control inhalation anesthetic concentration delivered to a patient based upon that patient's midlatency auditory evoked potentials (MLAEP's). It was developed and tested in dogs by determining response to the supramaximal stimulus of tail clamping. Prior to tail clamp, the MLAEP was recorded along with inhalational anesthetic concentration and classified as responders or nonresponders as determined by tail clamping. This was performed at a number of different anesthetic levels to obtain a data training set. The MLAEP's were compacted by means of discrete time wavelet transform (DTWT), and together with anesthetic concentration value, a stepwise discriminant analysis (SDA) was performed to determine those features which could separate responders from nonresponders. It was determined that only three features were necessary for this recognition. These features were then used to train a four-layer artificial neural network (ANN) to separate the responders from nonresponders. The network was tested using a separate set of data, resulting in a 93% recognition rate in the anesthetic transition zone between responders and nonresponders, and 100% recognition rate outside this zone. The anesthetic controller used this ANN combined with fuzzy logic and rule-based control. A set of ten animal experiments were performed to test the robustness of this controller. Acceptable clinical performance was obtained, showing the feasibility of this approach.
Anesthesia↗
Superinfection with rifampin-isoniazid-streptomycin-ethambutol (RISE)-resistant tuberculosis in three patients with AIDS: confirmation by polymerase chain reaction fingerprinting.
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AIDS-Related Opportunistic Infections↗
The suppression of long-term potentiation in rat hippocampus by inhibitors of nitric oxide synthase is temperature and age dependent.
At room temperature (23 degrees C-25 degrees C), the induction of long-term potentiation (LTP) in area CA1 of slices from young male Sprague-Dawley rats was depressed by preincubation with the nitric oxide synthase inhibitors NG-nitro-L-arginine (L-NA, 100 microM) and NG-nitro-L-arginine methyl ester (L-NAME, 100 microM). The D isomers were ineffective under the same conditions. Hemoglobin (20 microM) reduced but did not completely block LTP. Neither L-NA (at concentrations up to 1 mM) nor hemoglobin (20 microM) had any significant effect on LTP in slices from adult rats at room temperature, or in young rats at 29 degrees C-30 degrees C. These results suggest that nitric oxide is unlikely to play a role in the induction of LTP under physiological conditions.
Aging↗
Chloramine-T as a titrant for the determination of some selected antibiotics.
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Anti-Infective Agents, Local↗
Studies on heterocyclic compounds: Part I--Thiazole esters as anticholinergics.
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Animals↗
Time-frequency spectral representation of the EEG as an aid in the detection of depth of anesthesia.
A time-frequency spectral representation (TFSR) has been used to study the nonstationary information in the EEG as an aid in determining the anesthetic depth. This paper uses a TFSR with an exponential weighting function for the purpose. Raw EEG data were collected form 10 mongrel dogs at various levels of halothane anesthesia. Depth of anesthesia was tested by observing the response to tail clamping, which is considered a supramaximal stimulus in dogs. A positive response was graded as awake (depth 0), and a negative response was graded as asleep (depth 1). The EEG obtained during a period of 30 sec tail clamp was processed into TFSRs. It was observed that at depth 0, the spectrum becomes localized in time and frequency. The percentage of energy in the delta (1-3.5 Hz) and theta (3.5-7.5 Hz) frequency bands increased. At depth 1, the spectrum remained unchanged throughout the period of tail clamp. The performance of the TFSR in detecting the patient's awareness was also compared with the power spectrum. It was concluded that under certain anesthetic conditions, the TFSR is superior to the power spectrum.
Anesthesia↗
Primary AL (kappa-light chain) amyloidosis manifesting as peripheral neuropathy in a young male without increase in serum and urine immunoglobulin load: a diagnostic challenge.
Primary systemic or AL amyloidosis is a multisystem disorder characterized by diffuse extracellular infiltration of a fibrillar protein of monoclonal light chain origin (AL). Majority of the patients have monoclonal immunoglobulin in serum and/or urine and some have clonal proliferation of plasma cells in their bone marrow. This disease has the widest spectrum of organ involvement, most commonly affecting the kidneys, heart and liver. Involvement of peripheral nervous system is not infrequent and may be the presenting feature of the disease process. Thus, recognition of peripheral neuropathy and affecting the kidney as an early symptom of AL amyloidosis may widen the scope for therapeutic intervention. We describe here a rare case of primary amyloidosis (AL) kappa-light chain presenting with clinical features of peripheral neuropathy and affecting the kidney and heart at an early age of 18 years, hitherto unreported in literature. The case was further interesting as it was not associated with increased serum/urine immunoglobulins or plasma cells in bone marrow. Diagnosis was confirmed using immuno-electron microscopy on sural nerve biopsy.
Adolescent↗