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Biomedical subjects

K Paul

Publications and source records attributed to K Paul.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effectiveness and safety of nizatidine, 75 mg, for the relief of episodic heartburn.

BACKGROUND: The most frequent cause of episodic heartburn is food and beverage ingestion. Nizatidine, an H2-receptor antagonist, is currently approved for non-prescription use in the prevention and relief of heartburn at a dose of 75 mg up to twice a day. METHODS: Two identical studies were carried out to evaluate the efficacy of nizatidine, 75 mg, compared with placebo in treating heartburn in an "at-home" setting. The studies were multicentre, multiple-dose, placebo-controlled, randomized, parallel group design. A total of 994 subjects were randomized to treatment. Adequate relief of heartburn was assessed at 15, 30 and 45 min and 1, 2 and 3 h following a treatment dose. A subject's responses with respect to time to relief and attainment of adequate relief were combined into a derived response profile, the sustained adequate relief score. Adverse experiences were noted throughout the study period. RESULTS: The individual and combined study results showed that nizatidine, 75 mg, relieved heartburn faster and/or more consistently than placebo. The mean sustained adequate relief score, calculated over a subject's first four episodes, was 2.43 in the nizatidine-treated group compared with 2.14 in the placebo group (P < 0.001). Nizatidine-treated subjects attained sustained adequate relief in a significantly (P < 0.001) larger percentage (75%) of their heartburn episodes than did subjects treated with placebo (66%). No serious adverse experiences were associated with nizatidine treatment. CONCLUSION: Nizatidine, 75 mg, is a safe and effective treatment for episodic heartburn. The results showed that subjects taking nizatidine had heartburn relief that was achieved faster and/or more reliably than did subjects taking placebo.

Adolescent↗
PubMed2001

Chronic arsenic toxicity in Bangladesh and West Bengal, India--a review and commentary.

Fifty districts of Bangladesh and 9 districts in West Bengal, India have arsenic levels in groundwater above the World Health Organization's maximum permissible limit of 50 microg/L. The area and population of 50 districts of Bangladesh and 9 districts in West Bengal are 118,849 km2 and 104.9 million and 38,865 km2 and 42.7 million, respectively. Our current data show arsenic levels above 50 microg/ L in 2000 villages, 178 police stations of 50 affected districts in Bangladesh and 2600 villages, 74 police stations/blocks of 9 affected districts in West Bengal. We have so far analyzed 34,000 and 101,934 hand tube-well water samples from Bangladesh and West Bengal respectively by FI-HG-AAS of which 56% and 52%, respectively, contained arsenic above 10 microg/L and 37% and 25% arsenic above 50 microg/L. In our preliminary study 18,000 persons in Bangladesh and 86,000 persons in West Bengal were clinically examined in arsenic-affected districts. Of them, 3695 (20.6% including 6.11% children) in Bangladesh and 8500 (9.8% including 1.7% children) in West Bengal had arsenical dermatological features. Symptoms of chronic arsenic toxicity developed insidiously after 6 months to 2 years or more of exposure. The time of onset depends on the concentration of arsenic in the drinking water, volume of intake, and the health and nutritional status of individuals. Major dermatological signs are diffuse or spotted melanosis, leucomelanosis, and keratosis. Chronic arsenicosis is a multisystem disorder. Apart from generalized weakness, appetite and weight loss, and anemia, our patients had symptoms relating to involvement of the lungs, gastrointestinal system, liver, spleen, genitourinary system, hemopoietic system, eyes, nervous system, and cardiovascular system. We found evidence of arsenic neuropathy in 37.3% (154 of 413 cases) in one group and 86.8% (33 of 38 cases) in another. Most of these cases had mild and predominantly sensory neuropathy. Central nervous system involvement was evident with and without neuropathy. Electrodiagnostic studies proved helpful for the diagnosis of neurological involvement. Advanced neglected cases with many years of exposure presented with cancer of skin and of the lung, liver, kidney, and bladder. The diagnosis of subclinical arsenicosis was made in 83%, 93%, and 95% of hair, nail and urine samples, respectively, in Bangladesh; and 57%, 83%, and 89% of hair, nail, and urine samples, respectively in West Bengal. Approximately 90% of children below 11 years of age living in the affected areas show hair and nail arsenic above the normal level. Children appear to have a higher body burden than adults despite fewer dermatological manifestations. Limited trials of 4 arsenic chelators in the treatment of chronic arsenic toxicity in West Bengal over the last 2 decades do not provide any clinical, biochemical, or histopathological benefit except for the accompanying preliminary report of clinical benefit with dimercaptopropanesulfonate therapy. Extensive efforts are needed in both countries to combat the arsenic crisis including control of tube-wells, watershed management with effective use of the prodigious supplies of surface water, traditional water management, public awareness programs, and education concerning the apparent benefits of optimal nutrition.

Adult↗
PubMed2001

Effect of glucocorticoid therapy on glucocorticoid receptors in children with autoimmune diseases.

Low-dose glucocorticoids (GC) achieve their action completely by classical genomic effects, mediated by the glucocorticoid receptor (GCR). In high doses of GC, nongenomic effects have also been found, but it is still unclear to what extent they contribute to a beneficial outcome. In this study, we present a determination of the number of lymphocyte GCR sites and the binding affinity in healthy children and children with autoimmune diseases. We further assess the effect of GC administration, especially of high-dose pulse therapy on the number of binding sites. The number of GCR sites per cell was analyzed with [(3)H]-dexamethasone radioligand binding assay and binding affinity (Kd given in nM) in peripheral blood mononuclear cells isolated from 48 healthy children and 35 patients. The patients were divided into three groups based on GC treatment: 0 mg/kg (group 1), 0.01-0.3 mg/kg orally (group 2), and 10-15 mg/kg i.v. pulse therapy (group 3) of prednisolone equivalent per day. Gender- and age-independent normal values of 4338 +/- 1687 sites/lymphocytes and Kd 6.7 +/- 2.2 nM were found. At 3463 +/- 1574, the number of receptor sites in patients without GC (group 1) was significantly lower than that of healthy volunteers (p < 0.05). In patients receiving GC treatment, this value was reduced to 2952 +/- 512 (group 2). Significant down-regulation to a minimum of 479 +/- 168 (group 3) was found after pulse therapy compared with untreated patients (p < 0.01). In pulse therapy, GC lead to a fast and dramatic receptor down-regulation. We suppose that the increase in therapeutic success of pulse-therapy may partly be mediated through additional nongenomic effects.

Adolescent↗
PubMed2000

On surviving cancer.

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Adaptation, Psychological↗
PubMed2000

Fractional analysis of bronchoalveolar lavage fluid cytology in cystic fibrosis patients with normal lung function. Bronchoalveolar lavage for the evaluation of anti-inflammatory treatment (BEAT) study group.

Cystic fibrosis (CF) is associated with a neutrophil dominated airway inflammation. So far bronchoalveolar lavage (BAL) studies in CF have used pooled BAL samples which may be more representative of the alveolar compartment rather than the airways. To assess whether the first sample of a BAL is more sensitive in the evaluation of airway inflammation, the authors have studied 105 stable CF patients aged 5-37 yrs with a mean forced expiratory volume in one second (FEV1) of 96+/-15% (mean+/-SD). BAL cytology of the first and pooled samples were compared to reference values obtained in children without respiratory disease. Absolute cell counts and the percentage of neutrophils were significantly increased in CF patients. If the 95% confidence interval was used as a cut-off point, 17/105 CF patients had a normal percentage of neutrophils in pooled BAL samples, but only three also had a normal percentage of neutrophils in the first BAL aliquot. Therefore, neutrophil dominated airway inflammation is more pronounced in the first, mainly bronchial, bronchoalveolar lavage sample suggesting that sequential analysis of bronchoalveolar lavage fluid may have a higher sensitivity to detect early inflammatory changes in CF patients.

Adolescent↗
PubMed2000

Treatment of nonresectable hepatocellular carcinoma with intrahepatic 90Y-microspheres.

UNLABELLED: Treatment for nonresectable hepatocellular carcinoma (HCC) is palliative. The relatively greater arteriolar density of hepatic tumors compared with normal liver suggests that intrahepatic arterial administration of 90Y-microspheres can be selectively deposited in tumor nodules and results in significantly greater radiation exposure to the tumor than external irradiation. The purpose of this study was to determine the proportion (frequency) and duration of response, survival, and toxicity after intrahepatic arterial injection of 90Y-microspheres in patients with HCC. METHODS: Patients with documented HCC, Eastern Cooperative Oncology Group performance status 0-3, adequate bone marrow, and hepatic and pulmonary function were eligible for study. Patients who had significant shunting of blood to the lungs or gastrointestinal (GI) tract or who could not undergo cannulation of the hepatic artery were excluded. Patients received a planned dose of 100 Gy through a catheter placed into the hepatic artery. RESULTS: Twenty-two patients were treated with 90Y-microspheres; 20 of the treated patients (median age, 62.5 y) were evaluated for treatment efficacy. Nine patients were Okuda stage I, and 11 were Okuda stage II. The median dose delivered was 104 Gy (range, 46-145 Gy). All 22 treated patients experienced at least 1 adverse event. Of the 31 (15%) serious adverse events, the most common were elevations in liver enzymes and bilirubin and upper GI ulceration. The response rate was 20%. The median duration of response was 127 wk; the median survival was 54 wk. Multivariable analysis suggested that a dose >104 Gy (P = 0.06), tumor-to-liver activity uptake ratio >2 (P = 0.06), and Okuda stage I (P = 0.07) were associated with longer survival. CONCLUSION: Significantly higher doses of radiation can be delivered to a HCC tumor by intrahepatic arterial administration of 90Y-microspheres than by external beam radiation. This treatment appears to be beneficial in nonresectable HCC with acceptable toxicity.

Brachytherapy↗
PubMed2000

[Regular respiration during sleep in children in the first months of life].

Regular respiration is an important parameter of quiet sleep in infants. At the earliest age, the periods of regular respiration are shorter as compared with the periods of EEG, EMG and EOG patterns of quiet sleep. The duration of periods with regular respiration significantly increases with age, and their coincidence with other parameters of quiet sleep becomes higher. The frequency of regular respiration significantly decreases with age. Very short periods of regular respiration, low coincidence with other parameters of quiet sleep, and very high frequency of regular respiration after the 12th week of life may indicate a delay in the central nervous system development.

Aging↗
PubMed1999

Effects of dietary supplementation of saturated fatty acids and of n-6 or n-3 polyunsaturated fatty acids on plasma and red blood cell membrane phospholipids and deformability in weanling guinea pigs.

The fatty acid composition of plasma cholesteryl esters, plasma phospholipids, red blood cell (RBC) membrane phosphatidylcholine (corresponding to the outer membrane leaflet), and phosphatidylethanolamine (corresponding to the inner membrane leaflet) was investigated in weanling guinea pigs fed with diets of cacao (saturated fatty acids), sunflower oil [n-6 polyunsaturated fatty acids (PUFA)] or fish oil (n-3 PUFA) for 20 wk. RBC deformation was measured by means of a cell-transit analyzer (filtration) and a cone-plate rheoscope. The contents of saturated fatty acids in plasma phospholipids and RBC membrane leaflets were similar in all three groups. Diets with sunflower oil resulted in a high content of linoleic acid in plasma cholesteryl esters and in the outer leaflet of RBC membranes. Fatty acids of fish oil were mainly incorporated in plasma phospholipids and in the inner leaflet of RBC membranes. The arachidonic acid content was high in all groups in the plasma phospholipids and in the inner leaflet. The n-6 and n-3 PUFA were mainly incorporated in the inner leaflet. In all groups the polyunsaturated/saturated fatty acid ratio and the total PUFA content were similar in the inner RBC membrane. The RBC filtration times and the RBC deformation indices were not affected by the dietary treatment.

Animals↗
PubMed1999

Decreased levels of nitrosothiols in the lower airways of patients with cystic fibrosis and normal pulmonary function.

Airway S-nitrosothiols (SNOs) are naturally occurring bronchodilators. SNOs, nitrate, and nitrite were measured in bronchoalveolar lavage fluid of 23 patients with cystic fibrosis (CF) and mild pulmonary disease (aged 6-16 years) and 13 healthy children (aged 8-15 years). Concentrations of SNOs were decreased in the lower airways of patients with CF and mild pulmonary disease (median, range: 0, 0-320 nmol/L vs 80, 0-970 nmol/L) despite normal levels of the inert nitric oxide metabolites nitrate and nitrite (mean +/- SEM: 3.7 +/- 0.5 micromol/L vs 4.8 +/- 0.9 micromol/L). S-nitrosolation- mediated bioreactivities may be impaired by depletion of the CF airway SNO reservoir.

Adolescent↗
PubMed1999

Increasing dose of methylprednisolone pulse therapy treats desquamative interstitial pneumonia in a child.

A 10 yr old male with hypoxaemia, progressive infiltration on the chest radiograph and biopsy-proven desquamative interstitial pneumonia was treated with daily oral prednisolone for 6 months. Intravenous methylprednisolone pulses were concomitantly administered in doses averaging 10 mg x kg body weight(-1) on three consecutive days every 4-6 weeks. After 6 months improvement could be noted and oral steroids were stopped, while pulse therapy continued. Three months later, when seven pulses had been administered, a relapse occurred and the clinical status deteriorated. Instead of reinstating daily systemic steroids, the dose of methylprednisolone pulses was increased to 20 mg x kg body weight(-1) i.v. given on three consecutive days and repeat pulses every 4 weeks. This was followed by continuous improvement. After 24 months corticosteroid pulses were terminated. Normal lung function, serum lactate dehydrogenase, blood gases upon exertion and regular development was achieved. During the course of treatment, the child has grown 10 cm. It is concluded that the effect of corticosteroid pulse therapy on interstitial lung disease in childhood is dose-dependent and that the dose can be adjusted to the effect observed.

Anti-Inflammatory Agents↗
PubMed1999

[Ambulatory vs. inpatient intravenous antibiotic therapy in mucoviscidosis patients--a controlled study].

METHODS: 14 patients with cystic fibrosis and chronic pulmonary pseudomonas infection received four courses of two-week intravenous antibiotic therapy at home and during hospitalisation over an 18-month period. Following a controlled, intra-individual cross-over design, two courses of home therapy were followed by two courses of hospital treatment or vice versa. Parameters for inflammation, lung function, and body mass index were obtained at the beginning and end of each intravenous antibiotic therapy. Health-related quality of life, i.e. physical, emotional, social and functional components as well as happiness and medical care, was assessed at the end of each course. RESULTS: There was a trend towards better reduction of infection (p = 0.20 for leukocyte reduction) and improvement of lung function (p = 0.20 for FEV1 improvement) with hospital intravenous antibiotic therapy, although the differences did not attain statistical significance. Quality of life during therapy was significantly higher with home therapy regarding social (p < 0.01), functional and emotional subscales and happiness (all p < 0.05). The necessity for professional help and support from family and/or partner was emphasised. Individual answers showed that home therapy has the advantage of self-determination and continuity of daily life. Parents and partners felt impaired by day and night intravenous therapy at home. CONCLUSION: From our data we conclude that home intravenous antibiotic therapy is a useful option for a selected subgroup of patients with cystic fibrosis, but professional support and family aid is important to gain an effect similar to hospital treatment.

Adolescent↗
PubMed1998

The combined influence of immunotherapy and mite allergen reduction on bronchial hyperresponsiveness in mite-sensitive asthmatic children.

UNLABELLED: Encasings for mattresses, blankets and pillows in combination with mite allergen reduction on the floor have proved effective in reducing bronchial hyperreactivity of mite-allergic children. We studied the effect of combining the use of encasings with specific immunotherapy in comparison to the use of encasings alone (control group). Twenty mite-allergic children (Skin Prick Test, RAST, mean age 10 years) with asthma and high domestic mite allergen exposure ( > 2 microg Der p 1 + f 1/g mattress dust) were included in our study. The concentration of these major allergens as well as specific and nonspecific bronchial hyperreactivity (PC20 FEV1 histamine) were assessed before, 6 months after and 1 year after start of treatment. All children received elongated polytetrafluorethylene (ePTFE; Goretex/Intervent Allergy Bedding System) encasings. A subgroup of eight children were treated additionally by specific immunotherapy with a partially purified mite extract (ALK Scherax) and a maximum dose of 100000 SQ-U Der p + f. Initially both groups were comparable with respect to the parameters assessed. In 80% of children, encasings reduced Der p 1 and Der f 1 concentrations on the mattress to below 3% of the initial values (P < 0.01). The median reduction was 99%. PC20 FEV1 histamine increased from 0.4 to 1.4 mg/dl (median) in the combined group with immunotherapy and encasings (P < 0.05) and remained essentially unchanged in the control group. PC20 FEV1 Der p did not increase significantly in either group. CONCLUSION: Specific immunotherapy with allergen extracts is an effective adjunct to encasings. Encasings, a key factor for reducing Der p 1 and Der f 1 on the mattress, should be used in combination with other avoidance measures (e.g. removal of carpets) in order to improve allergen-induced bronchial hyperreactivity.

Adolescent↗
PubMed1998

BCG infection suppresses allergic sensitization and development of increased airway reactivity in an animal model.

BACKGROUND: Epidemiologic studies suggest an inverse correlation between infections and development of atopy. The purpose of this study was to test the hypothesis whether a preexisting Th1-type immune response elicited by BCG immunization could suppress allergic sensitization and airway hyperreactivity in an animal model. METHODS: BALB/c mice were immunized with BCG and/or sensitized to ovalbumin. RESULTS: BCG immunization alone resulted in cutaneous type-IV hypersensitivity reactions to tuberculin and granulomatous lesions in the liver. Splenic mononuclear cells (MNCs) produced increased levels of IFN-gamma after activation by Concanavalin A (ConA). Ovalbumin sensitization alone resulted in increased production of IL-4 after activation by ConA. Ovalbumin-sensitized animals also demonstrated markedly elevated anti-ovalbumin IgE/IgG1 serum antibody titers and increased airway reactivity after allergen challenges by means of the airways. BCG immunization 14 days before the start of ovalbumin sensitization markedly hindered the development of allergic responses as indicated by (1) increased IFN-gamma and normalized IL-4 and IL-10 production by splenic MNCs after activation with ConA, (2) a reduced proliferation rate of splenic MNCs after ovalbumin restimulation, (3) partial prevention of ovalbumin-specific IgE/IgG1 serum antibody titers but elevated (nonallergic) anti-ovalbumin IgG2a serum antibody titers, (4) prevention of airway responsiveness, (5) reduced eosinophilic influx into the airway lumen, and (6) reduced levels of IL-4 and IL-5 in broncho alveolar lavage fluids. CONCLUSION: In this model BCG immunization established a Th1-type immune response that hinders allergic sensitization and the development of increased airway reactivity.

Animals↗