Pregnancy in a patient with prolactinoma off treatment.
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Adult↗
Biomedical subjects
S Kalra
Publications and source records attributed to S Kalra.
Biological markers in the diagnosis and treatment of ALS.
The care of patients with amyotrophic lateral sclerosis (ALS), which has classically focused on treatment of symptomatology, has now entered an encouraging new era of therapy targeted at the pathophysiology of the disease. However, an objective measure of disease progression and therapeutic response is sorely needed. Quantitative neuromuscular examinations, measurement of pulmonary function, disability scales, and even survival, are limited by variability due to a number of poorly controlled factors. Quantitative electromyography, positron emission tomography scanning, and magnetic cortical stimulation, provide potential objective indicators of disease progression, but require a large number of patients and a long observation period for adequate statistical power. We have examined the role of magnetic resonance spectroscopic imaging in detecting acute changes in motor cortical metabolism in response to riluzole therapy. N-acetylaspartate (NAA), the most prominent signal in proton spectra of normal brain, is a neuron-specific molecule. ALS patients were found to experience a significant increase in the NAA/creatine ratio within 3 weeks of initiation of riluzole therapy. As glutamate can trigger the generation of reactive oxygen species in neurons, we speculate that acute changes in NAA levels may reflect oxidative injury to mitochondria where NAA is synthesised. The advent of a useful test for upper motor neuron metabolic compromise may provide an objective, non-invasive, short duration measure with which to screen the efficacy of potential therapeutic agents for ALS.
Amyotrophic Lateral Sclerosis↗
A randomized, double-blind study comparing the effects of beclomethasone and fluticasone on bone density over two years.
Cross-sectional studies have suggested that asthmatic patients receiving high dose inhaled corticosteroids and intermittent courses of oral corticosteroids have reduced bone mass. This prospective 2-yr study was undertaken to evaluate changes in bone density of patients receiving high doses of inhaled corticosteroids. Patients (n = 33) (males aged 18-50 yrs, females aged 18-40 yrs) on inhaled corticosteroids 1,000-2,000 microg x day(-1), were randomized in a double-blind fashion to either fluticasone propionate (FP) 1,000 microg x day(-1) or beclomethasone dipropionate (BDP) 2,000 microg x day(-1). In parallel, three open control groups of the same age range were studied: asthmatics (n = 8) receiving low dose inhaled corticosteroids (< or =400 microg x day(-1)) (group A); chronic, severe asthmatics (n = 8) receiving oral corticosteroids (> or =10 mg x day(-1) (group B); and healthy untreated volunteers (n = 7) (group C). Bone densitometry scans (quantitative computed tomography (QCT) of spine; dual X-ray absorptiometry of spine, femoral neck, and single photon absorptiometry of forearm) were performed at baseline and after 6, 12 and 24 months of treatment. Biochemical bone marker measurements (serum osteocalcin, bone alkaline phosphatase, pro-collagen type 1 carboxy terminal propeptide, deoxypyridinoline and C-telopeptide of type 1 collagen) were collected every 3 months. Fifteen FP (mean age 36 yrs, six male) and 9 BDP patients (mean age 33 yrs, five male); completed the study. At 0 months, mean bone mineral density (BMD) was lower in patients receiving inhaled corticosteroids (both low dose and high dose) than in normal volunteers. In the FP-treated group, mean vertebral trabecular BMD quantitative computed tomography remained stable with no evidence of decline, whereas there was some decline in the BDP-treated group. The treatment difference between FP and BDP was statistically significant in favour of FP for quantitative computed tomography measurements after 12 months (p = 0.006) and 24 months (p = 0.004). This study suggests that over 24 months, changes in bone density are minimal in patients on high-dose inhaled corticosteroids.
Absorptiometry, Photon↗
An evaluation of oxidative stress in diabetes mellitus during uncontrolled and controlled state and after vitamin E supplementation.
OBJECTIVE: The study was conducted on 50 patients (10 insulin dependent diabetes mellitus (IDDM) and 40 non-insulin dependent diabetes mellitus (NIDDM) of recently diagnosed diabetes mellitus. The main objectives of the study were: 1. To evaluate oxidative stress at uncontrolled stage. 2. To evaluate the effect of optimal control on oxidative stress irrespective of type of drug therapy used. 3. To further evaluate the effect of vitamin E supplementation on oxidative stress after achieving optimal control. This was done in order to explore anti-oxidant effect of vitamin E. METHODS: Fifty patients of uncontrolled diabetes of less than 1 year duration and without any overt complications were studied. The parameters of oxidative stress included malonyl-di-aldehyde (MDA), reduced glutathione and vitamin E levels in the blood. They were done at three stages i.e. (a) In uncontrolled stage, (b) At controlled stage and (c) After 4 weeks of vitamin E supplementation in dosage of 400 mg daily. The parameters of control included fasting blood sugar < or = 140 mg%, post prandial < or = 200 mg and HbA1c < or = 7% (analysed by prepared kit). RESULTS: The significantly raised levels of MDA and decreased levels of reduced glutathione and vitamin E during uncontrolled stage of diabetes indicated free radical stress inducing lipid peroxidation. The significant fall of MDA and rise in reduced glutathione and vitamin E levels in blood after optimal control revealed its beneficial effect on oxidative stress. The levels were not normalised but still stayed higher than controls. After 4 weeks of vitamin E supplementation, further fall in MDA and rise in reduced glutathione suggested beneficial effect of vitamin E over and above the optimal control. Vitamin E estimation in blood at this stage did not constitute parameter of oxidative stress as it was provided from outside but was done to know the compliance of patients. Normalisation or near normalisation was not achieved with vitamin E therapy indicating persistence of oxidative stress. CONCLUSION: There was an evidence of oxidative stress in diabetes which decreased with optimal control and further declined after vitamin E supplementation indicating anti-oxidant effect of vitamin E alone. Normalisation of oxidative stress was not achieved. A further study is desired to study the effect of vitamin E for longer period at least 3-6 months before a definite conclusion is drawn.
Adult↗
Determination of submicromolar concentrations of neurotransmitter amino acids by fluorescence detection using a modification of the 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate method for amino acid analysis.
A sensitive method for quantitatively determining submicromolar levels of neurotransmitter amino acids (e.g. Asp, Glu and gamma-aminobutyric acid) in microdialysates from brain and cerebrospinal fluids is reported. 6-Aminoquinolyl-N-hydroxy-succinimidyl carbamate (AQC) was employed as the derivatization reagent, followed by HPLC separation and fluorescence detection of the derivatives. The derivatization was conducted simply by mixing the AQC directly with the microdialysis samples. The reaction was complete within seconds after mixing at room temperature. Separation development optimizing the gradient profile, eluent pH and column temperature resulted in an excellent separation of the required amino acids in less than 30 min. Other resolved amino acids in the same profile include Gly, taurine, and Pro. Recoveries for the amino acids of interest spiked into high salt containing perfusion buffers were greater than 97%. The sensitivity of the method was increased by employing a 16-microliter flow cell in the detector and analyzing 20-microliter aliquots of the derivatization mixtures. With the optimized conditions, the detection limits were 3-7 nM (fmol/microliter). Typical reproducibility (%R.S.D.) for quantitation of these amino acids at submicromolar levels was approximately 2%. Excellent linearity (r2 > 0.999) was achieved over the range 0.2-20 microM. The low detection limits permitted the analysis of a number of different microdialysate samples including those from cerebrospinal fluid, as well as substantia nigra and hypothalamus from brain samples, even at basal levels where gamma-aminobutyric acid concentration may be < 50 nM. The excellent sensitivity made it easy to distinguish basal from stimulated levels of neurotransmitter amino acids, even from sample sizes as small as 10 microliters.
Aminoquinolines↗
Recovery of N-acetylaspartate in corticomotor neurons of patients with ALS after riluzole therapy.
Riluzole, a glutamate antagonist, has been shown to be efficacious in the treatment of patients with amyotrophic lateral sclerosis (ALS), allowing prolonged survival and time to tracheostomy. The efficacy of riluzole in thought to result from reduced glutamate excitotoxicity on motor neurons of patients with ALS, but this has never been demonstrated directly in vivo. N-acetylaspartate (NAA), a compound that is readily measured in vivo using proton magnetic resonance spectroscopy, can be used as a surrogate marker for neuronal loss or sublethal injury. To determine whether riluzole reverses sublethal corticomotoneuron damage in patients with ALS we measured NAA/creatine (Cr) relative intensity ratios in the motor cortex before and after treatment with riluzole 50 mg bid. After 3 weeks of riluzole therapy in 11 patients NAA/Cr increased from 2.14 +/- 0.26 to 2.27 +/- 0.24 (p = 0.044), whereas, in 12 untreated patients NAA/Cr decreased from 2.17 +/- 0.20 to 2.08 +/- 0.20 (p = 0.099). Thus the change in NAA/Cr between the treated and untreated groups was 0.22 +/- 0.095 (p = 0.008). The magnitude of increase in NAA/Cr in those treated was not correlated with age, sex, duration of treatment or disease, the presence of probable or definite upper motor neuron (UMN) signs, bulbar features, or pre-treatment NAA/Cr. We conclude that magnetic resonance spectroscopy can provide a novel surrogate measure of neuronal integrity that demonstrates reversal of sublethal UMN injury in patients with ALS within weeks of initiating riluzole therapy.
Adult↗
Interleukin 6, but not ciliary neurotrophic factor or leukaemia inhibitory factor, is responsible for the acute phase response to turpentine-induced myositis.
The acute phase response to inflammation is mediated in part by the endogenous production of pro-inflammatory cytokines. Interleukin 6 (IL-6) and members of its superfamily, including ciliary neurotrophic factor (CNTF) and leukaemia inhibitory factor (LIF) have been implicated as primary mediators of the hepatic acute phase response. In the present report, mice suffering a turpentine-induced myositis were passively immunized with antibodies against either IL-6, CNTF or LIF. Passive immunization against IL-6 attenuated the anorexia and completely prevented the hypoalbuminaemia, and increases in the serum concentration of the acute phase reactants, amyloid P, amyloid A and seromucoid. In contrast, passive immunization against either CNTF or LIF failed to modulate the anorexia, weight loss or hepatic acute phase protein responses. The findings suggest that IL-6, but not other members of its superfamily, is primarily responsible for the hepatic acute phase response, and contributes to the anorexia, associated with turpentine-induced myositis.
Acute-Phase Reaction↗
Comparison of 3 different doses of budesonide and placebo on the early asthmatic response to inhaled allergen.
BACKGROUND: A simple laboratory method to evaluate relative potency of inhaled corticosteroids in asthma would be valuable. Single-dose studies with the allergen-induced late asthmatic response have failed to show a useful dose-response relationship. Treatment for several days with inhaled corticosteroids will also inhibit the allergen-induced early asthmatic response. METHODS: Twelve atopic asthmatic subjects were studied during a season when no medications were required except ipratropium bromide as needed. These subjects had positive allergen and methacholine inhalation tests and FEV1 greater than 70% of predicted value. A double-blind, randomized, cross-over study compared placebo and budesonide 100, 200, and 400 microg administered by means of Turbuhaler twice daily for 7 days with 6-day washout periods. Methacholine PC20 was measured before and after 6 days of treatment, and allergen PC15 was measured after 7 days of treatment. RESULTS: The allergen PC15 (n = 11) was significantly larger (P = .0001) for all doses of budesonide compared with placebo, but there was no significant difference between the 3 doses of budesonide, and no dose response was demonstrated. The methacholine PC20 was significantly larger after all budesonide treatments compared with placebo (P = .024), but there was no difference between the 3 doses. There was a progressive increase in the allergen PC15 chronologically (sequence effect) that was not explained by improvement in FEV1 or airway responsiveness; sequence effects were not seen for FEV1 or for pretreatment or posttreatment methacholine PC20. Statistical adjustment for sequence effect did not alter allergen PC15 statistics. CONCLUSION: A 7-day course of budesonide administered by means of Turbuhaler at 200, 400, or 800 microg per day provided marked and significant inhibition of the allergen-induced early asthmatic response compared with placebo. There was, however, no difference between the 3 doses. Therefore this method with these doses is not useful for providing assessment of relative potency.
Administration, Inhalation↗
Leptin produces anorexia and weight loss without inducing an acute phase response or protein wasting.
The ob gene product leptin is known to produce anorexia and loss of body fat when chronically administered to both lean and genetically obese mice. The current study was undertaken to examine whether administration of recombinant leptin in quantities sufficient to produce decreases in food intake and body weight and alterations in body composition would elicit either an hepatic acute phase protein response or preferential loss of carcass lean tissue. Mice were administered increasing quantities of recombinant human leptin or human tumor necrosis factor-alpha as a positive control. Although leptin (at 10 mg/kg body wt) produced significant anorexia and weight loss (both P < 0.05), human leptin administration did not appear to induce an hepatic acute phase protein response in either lean or genetically obese mice, as determined by protein synthetic rates in the liver or changes in the plasma concentration of the murine acute phase protein reactants, amyloid A, amyloid P, or seromucoid (alpha1-acid glycoprotein). In addition, human leptin administration did not induce a loss of fat-free dry mass (protein) in lean or obese animals. The findings suggest that at doses adequate to alter food intake and body weight leptin is not a significant inducer of the hepatic acute phase response nor does leptin promote the preferential loss of somatic protein characteristic of a chronic inflammatory process.
Acute-Phase Reaction↗
Subcapsular tubercular liver abscess.
A young female married for the last 2 years but without any issue presented with lump in the right upper abdomen. This was proved to be a subcapsular liver abscess on USG and CT scan and proved to be tubercular on needle aspiration cytology. She was given four drugs antitubercular treatment (ATT). After four months of ATT she conceived and it was decided by both parents to continue the pregnancy. The three drug ATT was continued throughout the pregnancy and she delivered a perfectly healthy baby. Upto three months follow up the mother and baby were perfectly healthy. The subcapsular tubercular liver abscess is extremely rare and conception during treatment may be the first case in literature.
Adult↗
Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response.
Inhaled allergens, acting through IgE-dependent mechanisms, are important triggers of asthma symptoms and inducers of airway hyperresponsiveness and airway inflammation. The effect of anti-IgE recombinant humanized monoclonal antibody-E25 (rhuMAb-E25) on the provocation concentration of allergen causing a 15% fall in FEV1 (allergen PC15) during the allergen-induced early asthmatic response (EAR) was assessed in a multicenter, randomized, double-blind, parallel group study. Ten of 11 allergic asthmatic subjects randomized to receive intravenous rhuMAb-E25, 2 mg/kg on study day 0 and 1 mg/kg on Days 7, 14, 28, 42, 56, and 70 completed the study; nine received intravenous placebo. The allergen PC15 was measured on Days -1, 27, 55, and 77 and methacholine PC20 on Days -2, 42, and 76. rhuMAb-25 was well tolerated and only one patient (active group) was withdrawn because of a generalized urticarial rash after the first dose. Compared with baseline values (Day -1), the median allergen PC15 on Days 27, 55, and 77 were increased by 2.3, 2.2, and 2.7 doubling doses (delta log PC15/0.3) respectively with rhuMAb-E25 and -0.3, +0.1, and -0.8 doubling doses with placebo (p < or = 0.002). Methacholine PC20 improved slightly after rhuMAb-E25, this change becoming statistically significant on Day 76 (p < 0.05); no change was observed in the placebo group. Mean serum-free IgE fell by 89% after rhuMAb-E25 while there was no significant change after placebo. The inhibitory effects of rhuMAb-E25 on allergen-induced EAR suggest that it may be an effective, novel antiallergic treatment for asthma.
Adult↗
Lewy body disease and dementia. A review.
Lewy bodies (LBs) are intracytoplasmic neuronal inclusions sometimes found in the brain stem, diencephalon, basal ganglia, and cerebral cortex. Cases designated as diffuse Lewy body disease (DLBD) demonstrate widespread cortical and subcortical Lewy body formation. The fact that DLBD is possibly the second most common cause of dementia after Alzheimer's disease is not generally recognized. We hope to emphasize the importance of this common neurodegenerative disorder by reviewing the literature and our own experience with DLBD. The English-language literature dealing with the clinical and pathological features of DLBD was reviewed. Pathological material from the Canadian Brain Tissue Bank, Toronto, Ontario, was reviewed over a 2-year period from 1991 through 1993. Prominent LB pathology may occur in isolation or mixed with pathological changes seen in Alzheimer's disease. Lewy body diseases include Parkinson's disease that presents with a classic movement disorder and sometimes dementia, and DLBD where LBs occur in a widespread distribution in the cortex in addition to the usual subcortical sites. Diffuse LB disease usually presents with a neurobehavioral syndrome that may include hallucinations, delusions, and psychosis; all patients eventually become demented. A day-to-day fluctuating mental state may be an important distinguishing clinical feature. Parkinsonism may follow the psychiatric disturbance although occasionally it is a presenting feature. Serious life- threatening side effects may occur with the use of standard neuroleptics. The variable clinical features and additional presence of Alzheimer-type pathological changes in many cases of DLBD has led to a confusing and inconsistent classification of LB disease and, together with little awareness of its existence, its misdiagnosis. Although DLBD may be the second most common cause of dementia, the terminology and classification of LB disorders and their relationship to Alzheimer's disease remain sources of intense debate. Further research is needed to resolve these issues and to provide insight into the pathogenesis of LB formation and accompanying neuronal degeneration.
Alzheimer Disease↗
Outpatient asthma management.
Asthma is an inflammatory disease. Educated asthmatics can be involved in self-managements strategies that focus on prevention and treatment of airway inflammation using environmental control and inhaled corticosteroids as the cornerstones of therapy. It is hoped that such an approach will reduce asthma morbidity and mortality rates.
Ambulatory Care↗
Inhaled corticosteroids do not prevent the development of tolerance to the bronchoprotective effect of salmeterol.
INTRODUCTION: Twice-daily inhaled salmeterol produces rapid reduction in its acute bronchoprotective effect against methacholine in patients with mild asthma. This investigation examined this effect in patients with moderate asthma who were using inhaled corticosteroids. SUBJECTS AND METHODS: Eight asthmatic volunteers who required inhaled corticosteroids for control of their symptoms and who were able to withhold treatment with beta 2-agonists for 4 weeks before and during the study participated in a double-blind, crossover, placebo-controlled study with two random-order treatment periods: inhaled salmeterol, 50 microg twice a day for seven doses, and placebo in similar fashion, with a 7-day or greater washout between these periods. Methacholine inhalation tests were done 1 h after doses 1, 3, 5, and 7, and then 24 h after the last dose of the study inhaler, 10 min post-200 microg salbutamol. RESULTS: Baseline FEV1 measurements before doses 3, 5, and 7 of salmeterol, ie, 12 h after salmeterol, were significantly higher than all other baseline values. Twenty-four hours after the last dose of salmeterol, the FEV1 was no different from that during the placebo period. The geometric mean methacholine concentration causing a 20% fall in FEV1 (PC20) following the third dose of salmeterol (6.8 mg/mL) was significantly lower than after the first dose of salmeterol (12.0 mg/mL; p=0.031), and this reduction of bronchoprotection persisted following doses 5 and 7. The methacholine PC20 10 min postsalbutamol measured after the salmeterol period was significantly lower than after placebo (5.6 vs 13.3 mg/mL; p<0.001). CONCLUSIONS: Tolerance to the acute bronchoprotective effect of salmeterol was significant after the first two doses and persisted after the seventh dose. Tolerance to the acute bronchoprotective effect of salbutamol was also significant after regular use of salmeterol for seven doses. These effects, in subjects using inhaled corticosteroids regularly, were similar to the those previously seen in patients with mild asthma using as-required beta 2-agonists only, indicating that tolerance is not prevented by use of inhaled corticosteroids.
Administration, Inhalation↗
Determination of post-salbutamol methacholine dose shift.
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Adrenergic beta-Agonists↗
Bronchial responsiveness of non-smoking women exposed to environmental tobacco smoke or biomass fuel combustion.
We studied bronchial responsiveness (BR) in three groups of housewives with or without history of exposure to tobacco smoke or combustion of biomass fuels. Methacholine bronchoprovocation test was used to study BR. The group I subjects (60), who served as controls, were nonsmokers and had no chronic exposure to passive smoking or environmental tobacco smoke (ETS) or biomass fuels. Three of these women showed a 20 per cent FEV1 fall with a cumulative methacholine dose of 72.5 mg or less. Of 60 women in group II (ETS-exposure) and 52 in group III (biomass exposure), 26 (43.3%) and 10 (19.2%) respectively showed bronchial hyper-responsiveness (BHR). The odds ratios for BHR in groups II and III were 14.53 and 4.52 respectively. The number of hyper-responders was significantly more and the mean PD20 less in the exposed than the non-exposed groups. The occurrence of BHR in the ETS exposed group was more (P < 0.05) than the biomass combustion group. There were more hyper-responders (both groups II and III) amongst those who had an exposure index (EI) of 50 or more compared to those with EI of less than 50. We conclude that chronic cumulative exposure to both ETS and biomass combustion produces significant BHR. Further, BHR developed more often on ETS exposure, and when the exposure was present for a longer period.
Adult↗
Inhaled beta 2-agonists and allergen-induced airway responses.
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Administration, Inhalation↗
Late carmustine lung fibrosis. Age at treatment may influence severity and survival.
Previously, we have reported in 1990 that 35% of carmustine treated patients (6 of 17) who survived childhood brain tumors died of pulmonary fibrosis between 2 and 13 years after treatment. In addition, 8 patients studied in 1989 (13 to 17 years post treatment), had physiologic and biopsy or radiologic evidence of pulmonary fibrosis. We now report 3 more years of follow-up on these patients. Between 1989 and 1992, two more patients have died of pulmonary fibrosis, giving an overall mortality of 47%. Of the eight patients who died of pulmonary fibrosis, the median age at treatment was 2.5 years, whereas the nine long-term survivors had a median age at treatment of 10 years. All five patients treated below the age of 5 years have died of lung fibrosis. Analysis by the standard survival curve method indicated that patients treated at an age less than 6 years were more likely to die than those treated at an age older than 7 years (p = 0.03). Of the nine survivors, seven were observed over 3 more years. There was a gradual decline in mean forced vital capacity from 55% predicted (range, 44 to 81) to 51% predicted (range, 41 to 72) and total lung capacity fell from 65% predicted (range, 51 to 89) to 57% predicted (range, 47 to 77).
Adolescent↗