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PubMedDate not supplied

The linear relationship between changes in childhood growth velocity and topical glucocorticoid dose.

The concept of therapeutic indices for glucocorticoid treatment of rhinitis and asthma requires demonstration of the dose dependency of benefits and side effects. Therefore, we examined the relationship between glucocorticoid dose and changes in growth velocity (delta GV). The literature was reviewed for articles where the net delta GV could be calculated among steroid and parallel placebo, active treatment, or baseline run-in periods. Steroid dose and delta GV were analyzed by linear regression for 5 rhinitis and 19 asthma studies using topical budesonide, beclomethasone, fluticasone and mometasone, parenteral steroids, and nonsteroid comparitors. Dose dependency was established between 0 and the equivalent of 2000 micrograms/day of beclomethasone (r2 = 0.60). delta GV was not significantly affected by 200 micrograms/day of BDP or less. Nasal and bronchial administrations appeared to give equivalent responses. Growth suppression occurred within 2 weeks, and may be linked to a delay in the onset of puberty. The physiology of these effects was discussed.

Administration, Inhalation↗
PubMedDate not supplied

Allergic rhinitis jeopardizing the careers of professional singers, justifies intense therapy.

A series of three patients were evaluated and treated by the Northwestern University Section of Allergy. These patients had allergic disease that threatened their professional careers as performing artists. Although the clinical manifestations of allergic rhinitis were not unusually severe, these were sufficient to interfere with the performance of these professional singers. Because previous allergic diagnostic and therapeutic regimens had not controlled the voice related symptoms, career changes were reluctantly being considered. Unusually aggressive therapy including systemic corticosteroids was initiated as a diagnostic and therapeutic trial. The resultant improvement was then maintained with more standard allergic management and the three singers were able to perform satisfactorily. This report demonstrates how allergic disease affecting three performing artists justified intense therapy to prevent job loss and the potential financial, emotional and social consequences.

Administration, Inhalation↗
PubMed1995

Randomized study of sulfamethoxazole-trimethoprim versus aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with AIDS.

In a prospective, randomized open-label trial, the efficacy of sulfamethoxazole-trimethoprim (SMX-TMP) 400/80 mg b.i.d. was compared with the efficacy of aerosolized pentamidine (AP) 60 mg every 2nd week as secondary prophylaxis (SP) against recurrence of Pneumocystis carinii pneumonia (PCP) in AIDS patients. 94 patients participated in the study, 47 in each group. The patients were observed for a mean period of 17.2 months. PCP recurred in the AP group in 8 cases, while 1 relapse occurred in the SMX-TMP group. The one-year cumulative relapse rate was 9.0% (95% CI 0-19%) in the AP group compared with 2.4% (95% CI 0-8%) in the SMX-TMP group (p < 0.05). The odds ratio was 4.2 (95% CI 0.5-39.8) in favour of SMX-TMP. Furthermore, we found a tendency towards a protective effect against toxoplasmosis in the SMX-TMP group, though there was no difference in survival between the two groups. There was no statistical difference in frequency of crossover from one therapy form to the other. Based on these data we recommend SMX-TMP for secondary PCP prophylaxis.

AIDS-Related Opportunistic Infections↗
PubMed1986

The acute toxicity and primary irritancy of 2,4-pentanedione.

2,4-Pentanedione was found to have acute peroral LD50 values (with 95% confidence limits) in the rat of 0.78 (0.66-0.91) ml/kg for males and 0.59 (0.51-0.70) ml/kg for females, and acute percutaneous LD50 values by 24 hr occluded contact on the rabbit of 1.41 (0.80-2.49) ml/kg for males and 0.81 (0.59-1.12) for females. Lt50 values for exposure of rats to saturated vapor atmospheres were 52 min (7060 ppm) for males and 55 min (7912 ppm) for females. The 4 hr LC50 value for rats was 1224 (1063-1409) ppm for combined male and female data. A 4 hr occluded contact with 0.5 ml produced mild local erythema and edema. Instillation of 0.1 ml into the inferior conjunctival sac, produced mild conjunctivitis of less than 24 hr duration without corneal injury.

Administration, Inhalation↗
PubMed1988

Acute toxicity and primary irritation of para-tertiary butylphenol.

Para-tertiary butylphenol [(PTBP); the Union Carbide Corporation trademark for this chemical is UCAR Butylphenol 4-T Flake] has applications as a raw material in the manufacture of resins and also as an industrial intermediate. Acute peroral LD50 values (95% confidence limits) of 5.4 (3.6-7.9) g/kg and 3.6 (3.0-4.4) g/kg were obtained for male and female albino rats, respectively. Occluded cutaneous applications of moistened PTBP at 16 g/kg for 24 hr produced no mortalities in male or female rabbits, but signs of local toxicity and irritation were apparent at the site of application. A 6 hr exposure to a substantially saturated vapor under static conditions produced no mortality, while a 4 hr exposure to a dynamically generated respirable dust aerosol at a concentration of 5.6 mg/L produced 20% mortality. Occluded dermal contact (4 hr) with 0.5 g moistened PTBP produced a range of effects from no reaction to necrosis. PTBP placed in the conjunctival sac of rabbits produced severe ocular injury which generally persisted for 21 days after exposure. The major hazard associated with acute exposure to PTBP appears to be the irritation produced by dermal or ocular contact.

Administration, Cutaneous↗
PubMedDate not supplied

Safety comparison of insecticide microencapsulation and investigation of its mechanism.

Four kinds of microencapsulated insecticides were prepared with fenthion, mevinphos, acetofenate and methylparathion. From observations made after the experiment it was found that type II microcapsules with polyurea capsule walls formed by interfacial polymerization had a special advantage: they had greatly enhanced safety in mice when administered via mouth, respiratory tract and skin. Type I microcapsules, with capsular walls of gelatin and Arabic gum formed through complex condensation, had no safety protection with oral administration. The mechanism of safety enhancement associated with type II microcapsules depends mainly on maintenance of microcapsule integrity within the digestive tract; type II microcapsules rarely disintegrated in the gastrointestinal tract and only about 5 per cent were ruptured. Of the small quantity of insecticide that leaked through the ruptured capsule walls, the amount absorbed by the digestive tract was not sufficient to kill the mice before the microcapsules were discharged in faeces--The amount of discharge within 48 hours exceeded 80 per cent. Administration of large numbers of microcapsules was necessary before sufficient insecticide could be absorbed by the digestive tract to cause lethal dosage; on post-mortem examination some microcapsules were found intact in the stomach and small intestine. Type I microcapsules, however, were totally disintegrated in the digestive tract and no traces could be found in the faeces; therefore their drug safety could not be increased.

Accident Prevention↗
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↗
PubMed1994

Glucocorticoid osteoporosis.

Glucocorticoids act on calcium metabolism at many levels to produce osteoporosis, the major pathogenic effect probably being an inhibition of bone formation. In men, this is likely to be contributed to by a dose-related reduction in circulating testosterone concentrations. Bone density is reduced 10-20% at the commonly assessed sites, but deficits of twice this magnitude are found in trabecular bone. Dose and duration of steroid treatment influence the degree of osteopenia, but biochemical indexes of calcium metabolism are not predictive. In managing a steroid-treated patient, bone densitometry is usually helpful. Those with low densities should optimize their calcium intake, and those with sex hormone deficiency should receive appropriate replacement therapy. If bone loss is severe or continues despite these measures, the addition of bisphosphonate, calcitonin, fluoride, or a vitamin D metabolite may be appropriate, according to local availability. Thiazide diuretics can be combined with all these regimens. If thiazide diuretics are combined with vitamin D or its metabolites, careful monitoring of serum calcium should be undertaken. Bone density should be monitored annually until it is stable.

Administration, Inhalation↗
PubMed1997

Symptomatic improvement following emergency department management of asthma: a pilot study of intramuscular dexamethasone versus oral prednisone.

Systemic corticosteroid therapy is an established adjunct to beta-adrenergic medications in acute exacerbations of asthma. To date, no study has defined the role of long-acting intramuscular preparations of corticosteroids in pediatric patients with asthma. A pilot study was conducted to prospectively compare symptomatic improvement following a single injection of intramuscular dexamethasone (IMD) to a 3-day regimen of oral prednisone (OP) for children with mild to moderate wheezing episodes that are responsive to nebulized medications in the Pediatric Emergency Department (PED). The following children presenting with acute exacerbations of asthma to the PED were eligible for enrollment: age 3-16 years; more than two prior wheezing episodes; mild to moderate wheezing; and oxygen saturation 95% or more in room air. The study patients were randomly assigned to receive either IMD (n = 21) or OP (n = 21) in addition to a standardized treatment regimen of nebulized albuterol. All of the children were clinically rated for wheezing severity by the Pulmonary Index (PI) score at regular intervals during the study. Discharge home was based on clinical improvement during treatment in the PED; patients who were admitted to the hospital were removed from the study. Follow-up was conducted the fifth day after discharge from the ED either by clinic visit or by telephone. Patients were assessed for symptomatic improvement and relapse or clinical deterioration during the study period by a clinician blinded to group assignment. Forty-two children participated in this pilot study. There were no significant differences between the IMD and OP groups for gender or age. Mean ages were: 82 months (SD 46 months), IMD group; 63 months (SD 36 months), OP group. Clinical progress (based on PI) with treatment in the PED was the same in both groups: pretreatment median, PI = 6; PED discharge median, PI = 2. None of the study patients were hospitalized during the follow-up period, and all reported symptomatic improvement since initial treatment. The data of this pilot study suggest that IMD may be a feasible alternative to OP for treatment of acute wheezing episodes in children with asthma. IMD provides sufficient treatment to prevent clinical deterioration within 5 days after initial therapy for mild to moderate pediatric exacerbations of asthma that are responsive to nebulized medications.

Administration, Inhalation↗
PubMed1998

Recent approaches in insulin delivery.

Insulin remains indispensable in the management of diabetes mellitus since its discovery in 1921. The foreignness of early available porcine and bovine insulin led to the development of human insulin by transpeptidation and biosynthesis in microorganisms. Needle phobia and stress of multiple daily injections led to the investigation and exploitation of all promising routes, ranging from nasal to rectal, by a wide variety of devices and delivery systems. This article describes the development of human insulin, various routes for delivery of insulin (including oral, nasal, buccal, rectal, and pulmonary), and various devices for regulated, safe, and convenient insulin delivery. The article reviews some recent advances in insulin delivery such as the bioresponsive and self-regulated insulin delivery system.

Administration, Inhalation↗
PubMed1994

In vivo evaluation of dosage forms: application of gamma scintigraphy to non-enteral routes of administration.

The trend to deliver drugs to defined areas of the body involves sophisticated carriers systems. In addition to the in vitro drug release profile one must be aware of the in vivo behaviour of the dosage form and the drug. Gamma scintigraphy is an elegant way to gain insights of the actual in vivo distribution pattern of dosage forms. This technique relies on the use of radioactive tracers included into the medicament and selected so as to enable an optimum detection by a gamma ray camera. The choice of a convenient label enables the in vivo determination of the targeting of the formulation administered through a large number of routes. The present paper reviews applications of gamma scintigraphy for the evaluation of dosage forms administered by the parenteral, rectal, buccal, nasal, pulmonary, and ophthalmic routes.

Administration, Buccal↗
PubMed2001

Rapid up-regulation of CXC chemokines in the airways after Ag-specific CD4+ T cell activation.

Ag-specific activation of CD4(+) T cells is known to be causative for the cytokine production associated with lung allergy. Chemokine-induced leukocyte recruitment potentially represents a critical early event in Ag-induced lung inflammation. Whether Ag-specific, lung CD4(+) T cell activation is important in lung chemokine production is currently not clear. Using alphabeta-TCR transgenic BALB/c DO11.10 mice, we investigated the ability of Ag-specific CD4(+) T cell activation to induce lung chemokine production and leukocyte recruitment. Within 1 h of exposure of DO11. 10 mice to OVA aerosol, lung mRNA and protein for the neutrophil chemokines KC and macrophage inflammatory protein (MIP)-2 were greatly increased. Accordingly, neutrophils in the airways increased by >50-fold, and KC and MIP-2 proved to be functional because their neutralization significantly reduced airway neutrophilia. CD4(+) T cell activation was critical because CD4(+) but not CD8(+) T cell depletion reduced KC production, which correlated well with the previously observed inhibition of neutrophil influx after CD4(+) T cell depletion. In vitro studies confirmed that OVA-induced KC and MIP-2 production was conditional upon the interaction of CD4(+) T cells with APCs. A likely secondary mediator was TNF-alpha, and a probable source of these chemokines in the lung was alveolar macrophages. Thus, Ag-specific CD4(+) T cell activation in the lung leads to rapid up-regulation of neutrophil chemokines and the recruitment of neutrophils to the site of Ag exposure. This may be a key early event in the pathogenesis of Ag-induced lung inflammation.

Administration, Inhalation↗
PubMed2002

Surfactant protein D reduces alveolar macrophage apoptosis in vivo.

Surfactant protein D (SP-D) is a molecule of the innate immune system that recognizes the patterns of surface carbohydrate on pathogens and targets them for phagocytosis and killing. SP-D-deficient mice show an increased number of macrophages in the alveolar space, excess surfactant phospholipid, overproduction of reactive oxygen species, and the development of emphysema. We report here that SP-D-deficient mice have a 5- to 10-fold increase in the number of apoptotic and necrotic alveolar macrophages, as defined by annexin V and propidium iodine staining, respectively. Intrapulmonary administration of a truncated 60-kDa fragment of human recombinant SP-D reduces the number of apoptotic and necrotic alveolar macrophages and partially corrects the lipid accumulation in SP-D-deficient mice. The same SP-D fragment binds preferentially to apoptotic and necrotic alveolar macrophages in vitro, suggesting that SP-D contributes to immune homeostasis in the lung by recognizing and promoting removal of necrotic and apoptotic cells.

Administration, Inhalation↗