A pharmacokinetic comparison of the corn oil versus microemulsion gelcap formulation of cyclosporin used de novo after renal transplantation

The initial poor absorption of the corn oil-based, gel capsule oral formulation of cyclosporin (CyA) greatly limits its use for inception of immunosuppressive therapy. Insufficient drug concentrations during the early post-transplant period predispose to renal allograft rejection. The present study served to compare the time required to achieve therapeutic CyA concentrations after de novo administration of the corn oil-based gel capsule (CyA-GC; n = 11) versus the microemulsion (CyA-ME; n = 11) formulation of CyA. During the 1st month after renal transplantation, patients underwent serial pharmacokinetic profiling from which we obtained observed and dose-corrected values of several parameters. Although patients in neither the CyA-GC nor the CyA-ME group adequately absorbed the drug during days 0–2, from day 3 to 4 patients in the CyA-ME group showed significantly greater absorption than those in the CyA-GC group (P = 0.041). Patients in the CyA-ME group reached the 1st month target average concentration (C_av) values ( ≥ 550 ng/ml) earlier than those in the CyA-GC group and required significantly lower daily CyA doses (P = 0.018). We conclude that therapeutic CyA levels can be achieved more rapidly and with lower doses of the drug after de novo administration of CyA-ME than with CyA-GC. Received: 13 September 1996 Accepted: 7 January 1997     

The effect of cigarette smoke on the bovine lens

Smoking has recently been identified from epidemiological studies as a possible cause of cataract but the mechanism involved is not known. Therefore, our laboratory has initiated studies aimed at elucidating these mechanisms. Whole bovine lenses were cultured to examine possible effects of cigarette smoke on amino acid uptake and protein synthesis. Cigarette smoke, filtered to remove nicotine and tar which would not reach the eye in vivo, was bubbled through culture medium. Bovine lenses were incubated in this medium in the presence of [¹⁴C]-leucine for four days. A significant decrease in uptake of [¹⁴C]-leucine and a decrease in protein synthesis were found with smoke treated lenses. This is the first demonstration of an effect of cigarette smoke on the lens. Further work is needed to determine how this metabolic upset is mediated and how it could lead to cataract.     

Inpatient management of asthma in the Chicago suburbs: the Suburban Asthma Management Initiative (SAMI).

BACKGROUND: Assessment of inpatient asthma management has generally been limited to urban settings, including Chicago, which is known for its high asthma morbidity and mortality. Previously published data have been based on survey methodology. The Suburban Asthma Consortium (SAC) sought to obtain patient-based data unique to the Chicago suburbs to improve asthma care in those areas. OBJECTIVE: To evaluate current inpatient asthma management based on the 1997 National Asthma Education and Prevention Program (NAEPP). DESIGN: Retrospective chart review of all hospitalized patients 3-65 years bearing asthma-related ICD-9 codes for fiscal year 2002 in community, nonteaching hospitals in Chicago suburbs. RESULTS: Nine hundred two cases were submitted from seven hospitals. The majority ( > or = 75%) received inhaled bronchodilators, systemic steroids, oxygen and pulse oximetry. Antibiotic use (67%), chest radiography (85%), complete blood count (77%), and electrolytes (59%) appeared excessive in view of NAEPP recommendations. Peak flow monitoring (PFM) was recorded on admission in 45% of patients 5 years old and older; 52% had PFM during hospitalization. Thirty-eight percent of patients were taking ICS prior to admission; of those not on ICS, only 12% were newly diagnosed asthmatics. Overall, 51% of patients were discharged with ICS. Patients were more likely to receive ICS at discharge if they had required intensive care (ICU), had been on ICS prior to admission, were referred to an asthma specialist while hospitalized, or were insured. Patients with Medicare/Medicaid (MC/MA) had more repeat emergency visits and hospitalizations, longer lengths of stay, and received less ICS at discharge. Depending on the parameter, 41% or less patients received discharge planning education and were not more likely to have received education if in the ICU. Results ranged significantly between hospitals for most parameters (p < 0.05 or less). CONCLUSION: Study subjects received appropriate acute therapy and oxygen monitoring, but there was a divergence from NAEPP recommendations regarding PFM, ICS use, antibiotics, and laboratory evaluation. Patients receiving MC/MA experienced higher morbidity and received less ICS. Discharge asthma education was suboptimal for most hospitals. Most parameters demonstrated significantly wide practice variations between hospitals. Peak flow monitoring and patient education findings differed significantly from those in survey-conducted studies.     

Immature circulating lymphocytes in severely malnourished Guatemalan children

The percentage of peripheral blood lymphocytes forming rosettes with sheep erythrocytes (E-rosettes) was determined in 33 severely malnourished Guatemalan children, and in two groups of clinically well but mildly growth retarded children from the same environment. Mean E-rosettes in the acutely ill patients was lower than the value observed in the mildly malnourished children, although there was considerable overlap between groups. These data differ from previously published studies of severely malnourished children from other parts of the world in that not all patients had decreased values for E-rosettes, in contrast to the uniform depression reported by others. As all patients were clinically similar, the results suggest that there may be specific nutrient defects associated with protein-energy malnutrition that particularly affect immune function. In addition, in vitro incubation of lymphocytes from the acutely malnourished children with the thymic factor, thymosin fraction 5, increased the percentage of E-rosettes in a dose-dependent fashion. These data suggest that immature, thymosin-responsive T cells are present in circulation. It is possible that in vivo thymosin administration may be beneficial for malnourished individuals.