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Biomedical subjects

A K Kamada

Publications and source records attributed to A K Kamada.

At least 19 recordsLinked to original sources
PubMed1997

The safety of inhaled corticosteroid therapy in children.

Although discussed for many years, systemic adverse effects from inhaled corticosteroid therapy remains a complicated and controversial topic. It is by now well-known that inhaled corticosteroids may affect growth, bone, and adrenal function, yet the clinical relevance and the risks for such adverse effects are poorly defined. Earlier intervention, use of higher doses, differing potency claims, and new inhalers also affect the potential for systemic effects following inhaled administration. Until further research better characterizes these risks and identifies appropriate monitoring, caution in the use of this highly effective therapy is advised.

Administration, Inhalation↗
PubMed1996

Effect of ciprofloxacin on the pharmacokinetics and pharmacodynamics of warfarin.

To determine if ciprofloxacin therapy alters the response to warfarin treatment, 36 adult patients attending three university-affiliated outpatient anticoagulation clinics randomly received a 12-day course of ciprofloxacin (750 mg twice daily) and a 12-day course of placebo; each course was separated by a 2-week washout period. Prothrombin times (PTs), concentrations of S-warfarin and R-warfarin (the isomers of warfarin), and concentrations of clotting factors II and VII were determined three times weekly for 9 weeks. By day 12 of ciprofloxacin therapy, concentrations of S-warfarin remained unchanged compared with those after placebo therapy, but R-warfarin concentrations increased significantly (1.15 times those after placebo therapy; P = .001); concentrations of clotting factors II and VII decreased (0.903 and 0.872 times those after placebo therapy, respectively, P < or = .020). The mean PT ratio after 12 days of ciprofloxacin therapy increased slightly (1.032 times that after placebo therapy; P = .057), but no patient had bleeding or a change in PT that required alteration in warfarin or ciprofloxacin therapy. We conclude that warfarin therapy is not a contraindication to the use of ciprofloxacin.

Adult↗
PubMed1995

Glucocorticoids and growth in asthmatic children.

The effects of asthma and oral and inhaled glucocorticoid therapy on growth in children are reviewed. Previous reports have shown that asthma itself may delay the onset of puberty, an effect which may masquerade as growth suppression. Oral glucocorticoids appear to impair growth; however, lower doses and alternate-day therapy may have less risk of this effect. While a controversial topic, inhaled glucocorticoids in lower doses appear to be associated with a small risk of adverse effects on growth. Minimal data are available for higher doses. Knemometry, a relatively new technique used for measuring small changes in growth, has detected short-term effects with both oral and inhaled glucocorticoids therapy. However, a number of limitations are associated with short-term growth studies. Clinicians should be aware of the potential for growth impairment with glucocorticoid therapy so adequate monitoring can be undertaken and appropriate intervention introduced when deemed necessary.

Adolescent↗
PubMed1995

Special considerations in the use of glucocorticoids in children.

GCs are used commonly for the treatment of various inflammatory and autoimmune diseases. Although potent and generally effective, they are not without risks for producing serious adverse effects, especially when used in high doses for prolonged periods of time. Thus, the clinician must balance the therapeutic effects of GCs with their risks for adverse effects; using the lowest possible effective GC doses as well as maximizing other therapeutic modalities are means by which this goal can be achieved. Early recognition and appropriate management are other methods to minimize GC-induced adverse effects. Maximization of therapy, early recognition, and appropriate management of adverse effects can minimize the potential severe complications of GC therapy.

Chickenpox↗
PubMed1994

Coexistence of glucocorticoid receptor and pharmacokinetic abnormalities: factors that contribute to a poor response to treatment with glucocorticoids in children with asthma.

Rapid glucocorticoid clearance and abnormal glucocorticoid receptor binding have been described as factors that contribute to an inadequate response to treatment with glucocorticoids in patients with asthma. We report the coexistence of these abnormalities in children with severe asthma who respond poorly to systemic glucocorticoid therapy.

Adolescent↗
PubMed1994

Steroid-resistant asthma. Cellular mechanisms contributing to inadequate response to glucocorticoid therapy.

The current study examined whether alterations in glucocorticoid receptor (GR) binding contribute to poor response to glucocorticoid therapy in asthma. 29 asthma patients with forced expiratory volume in 1 s (FEV1) < 70% predicted were studied. Patients were classified as steroid sensitive (SS) if their morning FEV1 increased > 30% after a 1-wk course of oral prednisone 20 mg twice daily and steroid resistant (SR) if they failed to increase > 15%. PBMC obtained from these two groups, 17 SR and 12 SS, as well as 12 normal controls were analyzed. SR patients had two distinguishable GR binding abnormalities: 15 of the 17 SR patients demonstrated a significantly reduced GR binding affinity, as compared with SS patients (P = 0.0001) and normal controls (P = 0.0001). This defect was localized to T cells and reverted to normal after 48 h in culture media. However, incubation with a combination of IL-2 and IL-4 sustained this abnormality. The other two SR patients had an abnormally low GR number with normal binding affinity that was not limited to T cells. Furthermore, GR number failed to normalize after incubation in media alone or IL-2 and IL-4. Therefore, SR asthma may be due to more than one abnormality, the majority related to a reversible cytokine-induced reduction in GR binding affinity and the second related to an irreversible reduction in GR number. These findings may have important implications for the design of alternative treatment approaches for recalcitrant asthma.

Adult↗
PubMed1993

Efficacy and safety of low-dose troleandomycin therapy in children with severe, steroid-requiring asthma.

BACKGROUND: Troleandomycin (TAO), a macrolide antibiotic, was studied as an alternative treatment in 18 children with severe, steroid-requiring asthma. METHODS: In this investigation three treatment arms were used in randomized, double-blind, parallel fashion: combination TAO and methylprednisolone (MPn), combination TAO and prednisone, and MPn alone. RESULTS: All groups tolerated a considerable reduction in glucocorticoid dose over the 12 weeks of the study: 80% +/- 6% for TAO-MPn, 55% +/- 8% for TAO-prednisone, and 44% +/- 14% for MPn alone. These reductions are all statistically significant (p < 0.05) within groups, and the differences between groups were statistically significant between the TAO-MPn and MPn alone groups. The concentration of methacholine required to induce a 20% decrease in forced expiratory volume in 1 second and pulmonary function were not significantly improved in any treatment group. Safety parameters including blood chemistry and hematology, adrenal function assessment; bone densitometry, and muscle strength testing, were not altered significantly. Two patients who received TAO had elevated liver enzyme levels; one required discontinuation of TAO and one experienced spontaneous resolution without intervention. Lack of statistically significant changes in the efficacy parameters were likely a result of small sample size and effects of the glucocorticoid dose taper. CONCLUSIONS: TAO is safe and may be a reasonable treatment alternative in a limited trial for patients who are unable to tolerate tapering of their glucocorticoid dosage. Therapy should be guided by the goal of treatment, that is, glucocorticoid dose reduction or improvement of pulmonary function with appropriate monitoring of pulmonary function and adverse effects.

Adolescent↗
PubMed1992

Steroid resistance in asthma: our current understanding.

While much information has recently been obtained regarding the features of steroid-resistant asthma, it continues to be a dilemma for practitioners, and investigation into its mechanisms will remain an important part of asthma research. Until a clear marker defining steroid-resistant asthmatics is found, the principle first put forth by Carmichael and colleagues should be adhered to: that is, asthmatics resistant to glucocorticoid therapy need to be identified at an early stage so that unnecessary and perhaps harmful therapy can be discontinued. A 10 day course of high-dose (> or = 30 mg/day) systemic glucocorticoid therapy, as suggested by Kamada and colleagues, may constitute an adequate trial and may sufficiently identify asthmatics who may require alternative treatments. A more rational approach to the selection of alternative asthma treatments will be gained when the mechanisms of steroid resistance are identified.

Asthma↗
PubMed1992

Alternative treatments for asthma: assessing the need.

Alternative treatments such as troleandomycin methotrexate, gold, and intravenous gamma globulin are sometimes considered for severe asthmatics to minimize the need for systemic corticosteroids and reduce adverse effects. These alternative therapies may also be associated with significant toxicity and expense. The ability to reduce corticosteroid use and the need for alternative treatment interventions in 125 pediatric patients at our institution were reviewed. Because corticosteroid requirements were reduced significantly, only 23 of 125 children evaluated were considered for treatment alternatives with only 10 receiving such therapy. This study emphasizes the importance of a thorough and comprehensive review of corticosteroid requirements and usage prior to initiating alternative approaches to treatment in moderate to severe asthmatics as well as in patients thought to be "steroid-dependent."

Administration, Inhalation↗
PubMed1992

Effect of low-dose troleandomycin on theophylline clearance: implications for therapeutic drug monitoring.

Troleandomycin (TAO) is an alternative agent used in the treatment of severe, steroid-requiring asthma. Its mechanism of action, once thought to be inhibition of theophylline clearance, remains unclear. Twenty-four-hour theophylline profiles were obtained in 11 children with severe asthma prior to and after 2 and 12 weeks of low-dose TAO therapy. Theophylline dosages were adjusted by blinded investigators to maintain serum theophylline concentrations (STCs) between 10 and 20 micrograms/ml. Dosages were decreased from 877 +/- 60 mg/day (mean +/- SEM) before TAO to 811 +/- 56 mg/day (NS) after 2 weeks and 764 +/- 56 mg/day (p less than 0.05) after 12 weeks. Because of the dosage adjustments, STCs did not increase significantly. Theophylline clearance was reduced from 65.7 +/- 9.8 ml/kg/hour at baseline to 50.2 +/- 4.1 ml/kg/hour (p less than 0.05) after 2 weeks and 50.1 +/- 6.2 ml/kg/hour (p less than 0.05) after 12 weeks of TAO therapy. We conclude that TAO can significantly reduce theophylline clearance, resulting in increased STCs if dosages are not titrated. We recommend an empiric 25% reduction of daily theophylline dose with the initiation of TAO. We also recommend monitoring STCs 4 hours after the morning dose (with twice-daily dosing of sustained-release products) after 3, 7, 14, and 30 days of TAO therapy, then periodically as indicated.

Adolescent↗
PubMed1991

Pathogenesis of asthma: therapeutic implications.

The current knowledge of asthma, specifically an appreciation of the contributing mechanisms leading to its development as well as its clinical features, has increased vastly in recent years. A better understanding of asthma's inflammatory nature has resulted in wider use of antiinflammatory agents. Specific effects of available antiasthma medications have been better elucidated, thereby helping to focus the development of newer drugs and improve the use of currently available therapeutic agents. The purpose of this article is to further understanding of asthma by providing the pathologic and physiologic basis of this disease. This is vitally important information as it is shaping the directions of the therapeutic approach to asthma care.

Asthma↗