Journal of Krishna Institute of Medical Sciences University, 2016
Background: Uropathogens have an ability to form biofilm in urinary tract. Microorganisms growing... more Background: Uropathogens have an ability to form biofilm in urinary tract. Microorganisms growing in biofilm are associated with chronic and recurrent UTI. They are highly resistant to a variety of antimicrobial agents. There are different phenotypic methods to detect biofilm production like Tube Adherence Method (TAM), Congo Red Agar Method (CRAM), Tissue Culture Plate Method (TCPM), etc. Aim and Objectives: The purpose of the study was to observe biofilm formation by uropathogens, their antibiotic resistance pattern and to correlate biofilm formation with drug resistance. Material and Methods: Total 168 isolates were collected from urine over six months. They were subjected to AST by Kirby Bauer disc diffusion method. Detection of biofilm production was done by TAM, CRAM, and TCPM. Results: Escherichia coli was the commonest isolate. Of the 68 clinical isolates, 54% were positive for biofilm production by TAM, 58% by CRAM, and 66% by TCPM. Compared to non-biofilm producers higher ...
Background: Uropathogens have an ability to form biofilm in urinary tract. Microorganisms growing... more Background: Uropathogens have an ability to form biofilm in urinary tract. Microorganisms growing in biofilm are associated with chronic and recurrent UTI. They are highly resistant to a variety of antimicrobial agents. There are different phenotypic methods to detect biofilm production like Tube Adherence Method (TAM), Congo Red Agar Method (CRAM), Tissue Culture Plate Method (TCPM), etc. Aim and Objectives: The purpose of the study was to observe biofilm formation by uropathogens, their antibiotic resistance pattern and to correlate biofilm formation with drug resistance. Material and Methods: Total 168 isolates were collected from urine over six months. They were subjected to AST by Kirby Bauer disc diffusion method. Detection of biofilm production was done by TAM, CRAM, and TCPM. Results: Escherichia coli was the commonest isolate. Of the 68 clinical isolates, 54% were positive for biofilm production by TAM, 58% by CRAM, and 66% by TCPM. Compared to non-biofilm producers higher ...
This study was aimed to formulate and evaluate solid dispersion containing ivermectin to improve ... more This study was aimed to formulate and evaluate solid dispersion containing ivermectin to improve solubility. Ivermectin is BCS (Biopharmaceutical classification system) class-II drug, which has high permeability and low water solubility (0.005mg/ml) which is responsible for its poor dissolution rate and ultimately leads to variable absorption. Solid dispersion with Gelucire (44/14) has the ability to improve dissolution of poor water soluble drugs. So, solid dispersion ivermectin with Gelucire 44/14 was prepared to enhance the solubility and was further evaluated for different parameters such as assay, wettability, DSC, FT-IR, dissolution study.
The Journal of Clinical Endocrinology & Metabolism, 2009
Context: Hypertension (HTN) has been reported in up to 60% of children with Cushing syndrome (CS)... more Context: Hypertension (HTN) has been reported in up to 60% of children with Cushing syndrome (CS), but its course, side effects, and potential differences among various causes of CS have not been adequately studied. Objective: The objective of the study was to measure blood pressure in pediatric patients with CS before and after transphenoidal surgery or adrenalectomy and identify side effects and rates of residual HTN. Design: Data from 86 children with corticotropinomas ͓Cushing disease (CD)͔ and 27 children with ACTH-independent CS (AICS) were analyzed. Results: Patients with CD and AICS had significant HTN before surgery; more patients with AICS had systolic HTN (SHTN) than with CD (74 vs. 44%, P ϭ 0.0077), but the rate of diastolic HTN (DHTN) was similar. Both groups experienced significant decreases in SHTN immediately after transphenoidal surgery and adrenalectomy. One year postoperatively, both SHTN and DHTN were lower than the preoperative values in all patients, but as many as 16 and 4% of the patients with CD and 21 and 5% of the patients with AICS still had SHTN and DHTN, respectively. Higher blood pressure preoperatively correlated with cortisol levels. Two patients suffered serious side effects: one with multiple infarcts and another with hypertensive encephalopathy. Conclusions: Children with CS are at risk for residual HTN despite a significant improvement after surgical cure. HTN appears to correlate with the degree of hypercortisolemia. Serious HTN-related side effects, although rare, may occur during the perioperative period.
Objective-Pediatric Cushing disease (CD) often presents with short stature but we have observed s... more Objective-Pediatric Cushing disease (CD) often presents with short stature but we have observed significant inter-individual variability in the growth delay caused by endogenous hypercortisolism. Glucocorticoids cause growth retardation by affecting the growth hormone (GH)-insulin-like growth factor-1 (IGF 1) somatotropic axis, but also other, GH-independent sites. Recently, the GH receptor (GHR) gene was found to have a common polymorphism (P) that leads to a deletion (d3) or retention of exon 3. In this study, we tested the hypothesis that the GH receptor polymorphism (GHR-P) maybe one of the significant variants that determine the degree of growth delay among patients with CD. Design and methods-GHR genotyping was performed on 56 children with newly diagnosed CD (24 females, 32 males, mean age of 12.9±3.3 years) who were followed at our institution between the years 1997-2007. Correlation analysis included genotype, measures of growth and the somatotropic axis, and anthropometrics. Results-Within the group, 31 (12 girls, 19 boys) expressed the full length GHR allele, 10 (4 girls, 6 boys) were d3-GHR homozygotes and 15 (7 girls, 8 boys) were d3-GHR heterozygotes. No significant differences were found between the GHR genotypes and patient's height and or growth velocity, or any other measures that we evaluated. Conclusions-The presence of a well-studied and common GHR polymorphism does not appear to be responsible for the variability of growth delay observed in patients with Cushing disease.
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is classifi ed into three t... more Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is classifi ed into three types based on disease severity: classic saltwasting, classic simple virilizing, and nonclassic. Adrenomedullary dysplasia and epinephrine deficiency have been described in classic CAH, resulting in glucose dysregulation. Our objective was to investigate adrenomedullary function in nonclassic CAH and to evaluate adrenomedullary function according to disease severity. Adrenomedullary function was evaluated in response to a standardized cycle ergonometer test in 23 CAH patients (14 females, age 9-38 years; 6 salt-wasting, 7 simple virilizing, 5 nonclassic receiving glucocorticoid treatment, 5 nonclassic not receiving glucocorticoid), and 14 controls (7 females, age 12-38 years). Epinephrine, glucose, and cortisol were measured at baseline and peak exercise. CAH patients and controls were similar in age and anthropometric measures. Patients with nonclassic CAH who were not receiving glucocorticoid and controls experienced the expected stress-induced rise in epinephrine, glucose, and cortisol. Compared to controls, patients with all types of CAH receiving glucocorticoid had impaired exercise-induced changes in epinephrine (salt-wasting: p = 0.01; simple virilizing: p = 0.01; nonclassic: p = 0.03), and cortisol (saltwasting: p = 0.004; simple virilizing: p = 0.006; nonclassic: p = 0.03). Salt-wasting patients displayed the most significant impairment, including impairment in glucose response relative to controls (p = 0.03). Hydrocortisone dose was negatively correlated with epinephrine response (r = − 0.58; p = 0.007) and glucose response (r = − 0.60; p = 0.002). The present study demonstrates
The Journal of clinical endocrinology and metabolism, 2009
ACTH-independent macronodular adrenal hyperplasia (AIMAH) is often associated with subclinical co... more ACTH-independent macronodular adrenal hyperplasia (AIMAH) is often associated with subclinical cortisol secretion or atypical Cushing's syndrome (CS). We characterized a large series of patients of AIMAH and compared them with patients with other adrenocortical tumors.
The prevalence of germline mutations in MEN1, AIP, PRKAR1A, CDKN1B and CDKN2CI is unknown among p... more The prevalence of germline mutations in MEN1, AIP, PRKAR1A, CDKN1B and CDKN2CI is unknown among pediatric patients with pituitary adenomas (PA). In this study, we screened children with PA for mutations in these genes; somatic GNAS mutations were also studied in a limited number of growth hormone (GH) or prolactin (PRL)-secreting PA. We studied 74 and 6 patients with either isolated Cushing disease (CD) or GH-or PRL-secreting PA, respectively. We also screened 4 pediatric patients with CD, and 4 with GH/PRL-secreting tumors who had some syndromic feature. There was one AIP mutation (p.Lys103Arg) among 74 CD patients. Two MEN1 mutations that occurred in patients with recurrent or difficult to treat disease were found among syndromic CD patients. There was one MEN1 and 3 AIP mutations (p.Gln307ProfsX104, p.Pro114fsX, p.Lys241X) among pediatric patients with isolated GH-or PRL-secreting PA and one additional MEN1 mutation in a patient with positive family history. There were no mutations in the PRKAR1A, CDKN1B, CDKN2C or GNAS genes. Thus, germline AIP or MEN1 gene mutations are frequent among pediatric patients with GH-or PRL-secreting PA but are significantly rarer in pediatric CD; PRKAR1A mutations are not present in PA outside of Carney complex.
Purpose: Since the identification of PRKAR1A mutations in Carney complex, substitutions and small... more Purpose: Since the identification of PRKAR1A mutations in Carney complex, substitutions and small insertions/deletions have been found in ∼70% of the patients. To date, no germ-line PRKAR1A deletion and/or insertion exceeded a few base pairs (up to 15). Although a few families map to chromosome 2, it is possible that current sequencing techniques do not detect larger gene changes in PRKAR1A–mutation-negative individuals with Carney complex. Experimental Design: To screen for gross alterations of the PRKAR1A gene, we applied Southern hybridization analysis on 36 unrelated Carney complex patients who did not have small intragenic mutations or large aberrations in PRKAR1A, including the probands from two kindreds mapping to chromosome 2. Results: We found large PRKAR1A deletions in the germ-line of two patients with Carney complex, both sporadic cases; no changes were identified in the remaining patients, including the two chromosome-2-mapping families. In the first patient, the deleti...
Aim: To evaluate the pharmacokinetics (PK) and pharmacodynamics of the LFA3Ig fusion protein (LFA... more Aim: To evaluate the pharmacokinetics (PK) and pharmacodynamics of the LFA3Ig fusion protein (LFA3IgFP) in healthy volunteers and patients with chronic plaque psoriasis. Methods: The clinical trials included 2 phase I open studies. Study 1 was an open-label dose escalation study in 24 healthy volunteers, and study 2 was a single-group, open-label study in 12 patients with chronic plaque psoriasis. The serum drug concentrations were measured, and the concentration-time data were analyzed by compartmental analysis using the Practical Pharmacokinetic Program. Results: In study 1, after intramuscular (im) administration at a dosage of 5, 15, and 25 mg, the concentration-time curves of LFA3IgFP fitted well to a 1 compartment open model. Areas under the concentration-time curves increased linearly with dose. Clearance rates (Cls/ F) and elimination half-lives (T1/2ke) had no significant difference between different dose groups. A transient, slight decline of CD4 + and CD8 + T-cell subsets was observed after administration. In study 2, after im administration at a dosage of 15 mg weekly for 8 weeks, the concentration-time curve was best fitted to a 1 compartment open model, with a T1/2ke of 307.9±32.7 h. The steady state was attained after the fifth administration. Conclusion: The PK behaviors of LFA3IgFP in healthy volunteers and patients with chronic plaque psoriasis complied with linear kinetics within the examined dose range. A significant accumulation was observed after repeated administration at a dose of 15 mg weekly for 8 weeks.
Journal of Krishna Institute of Medical Sciences University, 2016
Background: Uropathogens have an ability to form biofilm in urinary tract. Microorganisms growing... more Background: Uropathogens have an ability to form biofilm in urinary tract. Microorganisms growing in biofilm are associated with chronic and recurrent UTI. They are highly resistant to a variety of antimicrobial agents. There are different phenotypic methods to detect biofilm production like Tube Adherence Method (TAM), Congo Red Agar Method (CRAM), Tissue Culture Plate Method (TCPM), etc. Aim and Objectives: The purpose of the study was to observe biofilm formation by uropathogens, their antibiotic resistance pattern and to correlate biofilm formation with drug resistance. Material and Methods: Total 168 isolates were collected from urine over six months. They were subjected to AST by Kirby Bauer disc diffusion method. Detection of biofilm production was done by TAM, CRAM, and TCPM. Results: Escherichia coli was the commonest isolate. Of the 68 clinical isolates, 54% were positive for biofilm production by TAM, 58% by CRAM, and 66% by TCPM. Compared to non-biofilm producers higher ...
Background: Uropathogens have an ability to form biofilm in urinary tract. Microorganisms growing... more Background: Uropathogens have an ability to form biofilm in urinary tract. Microorganisms growing in biofilm are associated with chronic and recurrent UTI. They are highly resistant to a variety of antimicrobial agents. There are different phenotypic methods to detect biofilm production like Tube Adherence Method (TAM), Congo Red Agar Method (CRAM), Tissue Culture Plate Method (TCPM), etc. Aim and Objectives: The purpose of the study was to observe biofilm formation by uropathogens, their antibiotic resistance pattern and to correlate biofilm formation with drug resistance. Material and Methods: Total 168 isolates were collected from urine over six months. They were subjected to AST by Kirby Bauer disc diffusion method. Detection of biofilm production was done by TAM, CRAM, and TCPM. Results: Escherichia coli was the commonest isolate. Of the 68 clinical isolates, 54% were positive for biofilm production by TAM, 58% by CRAM, and 66% by TCPM. Compared to non-biofilm producers higher ...
This study was aimed to formulate and evaluate solid dispersion containing ivermectin to improve ... more This study was aimed to formulate and evaluate solid dispersion containing ivermectin to improve solubility. Ivermectin is BCS (Biopharmaceutical classification system) class-II drug, which has high permeability and low water solubility (0.005mg/ml) which is responsible for its poor dissolution rate and ultimately leads to variable absorption. Solid dispersion with Gelucire (44/14) has the ability to improve dissolution of poor water soluble drugs. So, solid dispersion ivermectin with Gelucire 44/14 was prepared to enhance the solubility and was further evaluated for different parameters such as assay, wettability, DSC, FT-IR, dissolution study.
The Journal of Clinical Endocrinology & Metabolism, 2009
Context: Hypertension (HTN) has been reported in up to 60% of children with Cushing syndrome (CS)... more Context: Hypertension (HTN) has been reported in up to 60% of children with Cushing syndrome (CS), but its course, side effects, and potential differences among various causes of CS have not been adequately studied. Objective: The objective of the study was to measure blood pressure in pediatric patients with CS before and after transphenoidal surgery or adrenalectomy and identify side effects and rates of residual HTN. Design: Data from 86 children with corticotropinomas ͓Cushing disease (CD)͔ and 27 children with ACTH-independent CS (AICS) were analyzed. Results: Patients with CD and AICS had significant HTN before surgery; more patients with AICS had systolic HTN (SHTN) than with CD (74 vs. 44%, P ϭ 0.0077), but the rate of diastolic HTN (DHTN) was similar. Both groups experienced significant decreases in SHTN immediately after transphenoidal surgery and adrenalectomy. One year postoperatively, both SHTN and DHTN were lower than the preoperative values in all patients, but as many as 16 and 4% of the patients with CD and 21 and 5% of the patients with AICS still had SHTN and DHTN, respectively. Higher blood pressure preoperatively correlated with cortisol levels. Two patients suffered serious side effects: one with multiple infarcts and another with hypertensive encephalopathy. Conclusions: Children with CS are at risk for residual HTN despite a significant improvement after surgical cure. HTN appears to correlate with the degree of hypercortisolemia. Serious HTN-related side effects, although rare, may occur during the perioperative period.
Objective-Pediatric Cushing disease (CD) often presents with short stature but we have observed s... more Objective-Pediatric Cushing disease (CD) often presents with short stature but we have observed significant inter-individual variability in the growth delay caused by endogenous hypercortisolism. Glucocorticoids cause growth retardation by affecting the growth hormone (GH)-insulin-like growth factor-1 (IGF 1) somatotropic axis, but also other, GH-independent sites. Recently, the GH receptor (GHR) gene was found to have a common polymorphism (P) that leads to a deletion (d3) or retention of exon 3. In this study, we tested the hypothesis that the GH receptor polymorphism (GHR-P) maybe one of the significant variants that determine the degree of growth delay among patients with CD. Design and methods-GHR genotyping was performed on 56 children with newly diagnosed CD (24 females, 32 males, mean age of 12.9±3.3 years) who were followed at our institution between the years 1997-2007. Correlation analysis included genotype, measures of growth and the somatotropic axis, and anthropometrics. Results-Within the group, 31 (12 girls, 19 boys) expressed the full length GHR allele, 10 (4 girls, 6 boys) were d3-GHR homozygotes and 15 (7 girls, 8 boys) were d3-GHR heterozygotes. No significant differences were found between the GHR genotypes and patient's height and or growth velocity, or any other measures that we evaluated. Conclusions-The presence of a well-studied and common GHR polymorphism does not appear to be responsible for the variability of growth delay observed in patients with Cushing disease.
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is classifi ed into three t... more Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is classifi ed into three types based on disease severity: classic saltwasting, classic simple virilizing, and nonclassic. Adrenomedullary dysplasia and epinephrine deficiency have been described in classic CAH, resulting in glucose dysregulation. Our objective was to investigate adrenomedullary function in nonclassic CAH and to evaluate adrenomedullary function according to disease severity. Adrenomedullary function was evaluated in response to a standardized cycle ergonometer test in 23 CAH patients (14 females, age 9-38 years; 6 salt-wasting, 7 simple virilizing, 5 nonclassic receiving glucocorticoid treatment, 5 nonclassic not receiving glucocorticoid), and 14 controls (7 females, age 12-38 years). Epinephrine, glucose, and cortisol were measured at baseline and peak exercise. CAH patients and controls were similar in age and anthropometric measures. Patients with nonclassic CAH who were not receiving glucocorticoid and controls experienced the expected stress-induced rise in epinephrine, glucose, and cortisol. Compared to controls, patients with all types of CAH receiving glucocorticoid had impaired exercise-induced changes in epinephrine (salt-wasting: p = 0.01; simple virilizing: p = 0.01; nonclassic: p = 0.03), and cortisol (saltwasting: p = 0.004; simple virilizing: p = 0.006; nonclassic: p = 0.03). Salt-wasting patients displayed the most significant impairment, including impairment in glucose response relative to controls (p = 0.03). Hydrocortisone dose was negatively correlated with epinephrine response (r = − 0.58; p = 0.007) and glucose response (r = − 0.60; p = 0.002). The present study demonstrates
The Journal of clinical endocrinology and metabolism, 2009
ACTH-independent macronodular adrenal hyperplasia (AIMAH) is often associated with subclinical co... more ACTH-independent macronodular adrenal hyperplasia (AIMAH) is often associated with subclinical cortisol secretion or atypical Cushing's syndrome (CS). We characterized a large series of patients of AIMAH and compared them with patients with other adrenocortical tumors.
The prevalence of germline mutations in MEN1, AIP, PRKAR1A, CDKN1B and CDKN2CI is unknown among p... more The prevalence of germline mutations in MEN1, AIP, PRKAR1A, CDKN1B and CDKN2CI is unknown among pediatric patients with pituitary adenomas (PA). In this study, we screened children with PA for mutations in these genes; somatic GNAS mutations were also studied in a limited number of growth hormone (GH) or prolactin (PRL)-secreting PA. We studied 74 and 6 patients with either isolated Cushing disease (CD) or GH-or PRL-secreting PA, respectively. We also screened 4 pediatric patients with CD, and 4 with GH/PRL-secreting tumors who had some syndromic feature. There was one AIP mutation (p.Lys103Arg) among 74 CD patients. Two MEN1 mutations that occurred in patients with recurrent or difficult to treat disease were found among syndromic CD patients. There was one MEN1 and 3 AIP mutations (p.Gln307ProfsX104, p.Pro114fsX, p.Lys241X) among pediatric patients with isolated GH-or PRL-secreting PA and one additional MEN1 mutation in a patient with positive family history. There were no mutations in the PRKAR1A, CDKN1B, CDKN2C or GNAS genes. Thus, germline AIP or MEN1 gene mutations are frequent among pediatric patients with GH-or PRL-secreting PA but are significantly rarer in pediatric CD; PRKAR1A mutations are not present in PA outside of Carney complex.
Purpose: Since the identification of PRKAR1A mutations in Carney complex, substitutions and small... more Purpose: Since the identification of PRKAR1A mutations in Carney complex, substitutions and small insertions/deletions have been found in ∼70% of the patients. To date, no germ-line PRKAR1A deletion and/or insertion exceeded a few base pairs (up to 15). Although a few families map to chromosome 2, it is possible that current sequencing techniques do not detect larger gene changes in PRKAR1A–mutation-negative individuals with Carney complex. Experimental Design: To screen for gross alterations of the PRKAR1A gene, we applied Southern hybridization analysis on 36 unrelated Carney complex patients who did not have small intragenic mutations or large aberrations in PRKAR1A, including the probands from two kindreds mapping to chromosome 2. Results: We found large PRKAR1A deletions in the germ-line of two patients with Carney complex, both sporadic cases; no changes were identified in the remaining patients, including the two chromosome-2-mapping families. In the first patient, the deleti...
Aim: To evaluate the pharmacokinetics (PK) and pharmacodynamics of the LFA3Ig fusion protein (LFA... more Aim: To evaluate the pharmacokinetics (PK) and pharmacodynamics of the LFA3Ig fusion protein (LFA3IgFP) in healthy volunteers and patients with chronic plaque psoriasis. Methods: The clinical trials included 2 phase I open studies. Study 1 was an open-label dose escalation study in 24 healthy volunteers, and study 2 was a single-group, open-label study in 12 patients with chronic plaque psoriasis. The serum drug concentrations were measured, and the concentration-time data were analyzed by compartmental analysis using the Practical Pharmacokinetic Program. Results: In study 1, after intramuscular (im) administration at a dosage of 5, 15, and 25 mg, the concentration-time curves of LFA3IgFP fitted well to a 1 compartment open model. Areas under the concentration-time curves increased linearly with dose. Clearance rates (Cls/ F) and elimination half-lives (T1/2ke) had no significant difference between different dose groups. A transient, slight decline of CD4 + and CD8 + T-cell subsets was observed after administration. In study 2, after im administration at a dosage of 15 mg weekly for 8 weeks, the concentration-time curve was best fitted to a 1 compartment open model, with a T1/2ke of 307.9±32.7 h. The steady state was attained after the fifth administration. Conclusion: The PK behaviors of LFA3IgFP in healthy volunteers and patients with chronic plaque psoriasis complied with linear kinetics within the examined dose range. A significant accumulation was observed after repeated administration at a dose of 15 mg weekly for 8 weeks.
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