Prevalence of alpha-1 antitrypsin deficiency in poorly controlled asthma--results from the ALA-ACRC low-dose theophylline trial.

In a study comparing low-dose theophylline to montelukast in poorly controlled asthmatics, 285 subjects consented to be screened for alpha-1 antitrypsin deficiency. Of the 284 for which complete data was available, 10.5% carried a deficiency gene and 2.4% were mildly deficient with an alpha-1 antitrypsin serum level of less than 20 mu M. In the non-African-American cohort, an abnormal phenotype occurred in 12% and 2.9% were mildly deficient. Baseline pulmonary function and asthma scores were not significantly different between those with normal and abnormal AAT phenotype. However those with the deficiency tended to show a greater bronchodilator response.

Photographic measures of cytomegalovirus retinitis as surrogates for visual outcomes in treated patients.

OBJECTIVE: To evaluate photographic measures of cytomegalovirus (CMV) retinitis as surrogate outcomes for changes in vision in patients with CMV retinitis related to the acquired immunodeficiency syndrome. METHODS: Data from 3 clinical trials of CMV retinitis treatments were analyzed. Two photographic assessments of retinitis in eyes involved at baseline were evaluated: progression (lesion border movement > or = 750 microm or occurrence of a new lesion) and change in area of retina involved with retinitis. Vision measures were decline in best-corrected visual acuity and change in visual field. Photographic measures were evaluated as surrogate outcomes based on 4 criteria: (1) association with vision measure; (2) ability to account for treatment-related differences in vision measure; (3) data completeness; and (4) sample size requirements. RESULTS: Data from 1001 involved eyes (666 patients) were analyzed. Progression and change in area involved were predictive of declines in vision measures, accounted for 50% and 66% of the treatment effect on visual field, and were available from 93% and 64% of involved eyes, respectively. Sample size estimates for a clinical trial were smallest with progression as the design outcome. CONCLUSION: Progression and change in area involved met the first and second criteria for surrogate outcomes for visual field loss; a complete evaluation for visual acuity decline was not possible because treatment-related differences were not observed. Progression met the logistical and sample size criteria better than change in area of retina involved with retinitis.

Patient notification and follow-up after suspension of treatment protocols. experience from four clinical trials of treatments for AIDS-related CMV retinitis.

We reviewed procedures for and data about patient notification of the suspension of the treatment protocol for four clinical trials. We also examined how data collected after the suspensions were used. All four trials were designed to evaluate treatments for cytomegalovirus retinitis in patients with AIDS and were conducted by the Studies of Ocular Complications of AIDS Research Group. Documentation that patients were notified of the results varied from 62--100% with three of the four studies documenting the process for > or =92% of patients. The median time between the recommendation for protocol suspension and patient notification varied from 7--49 days with three of the four trials at 12 days or fewer. Most of the analyses of data collected after the suspension of the treatment protocol did not focus on comparisons among treatment groups. Although they provided useful information about the long-term outcomes and the nature of the disease, they did not alter the conclusions about safety and efficacy from the randomized portion of the trial. Control Clin Trials 2001;22:62-68

Risk factors for advancement of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome. Studies of Ocular Complications of AIDS Research Group.

OBJECTIVE: To identify ocular and systemic factors that predict advancement of cytomegalovirus (CMV) retinitis during treatment. METHODS: Patients with acquired immunodeficiency syndrome were enrolled in a multicenter clinical trial designed to evaluate foscarnet sodium and ganciclovir sodium as therapy for newly diagnosed CMV retinitis. Ocular characteristics at baseline and measurements of retinitis were assessed from fundus photographs by graders at a fundus photograph reading center. The following measures of advancement were assessed: (1) lesion border movement of at least 750 microm or development of a new lesion in involved eyes; (2) rate of increase in retinal area with CMV in involved eyes; and (3) development of retinitis in uninvolved eyes of patients with unilateral disease at baseline. RESULTS: In eyes with retinitis, risk factors at baseline for advancement while receiving treatment included smaller area involved, active margins of retinitis, and posterior location. Risk factors for development of retinitis in uninvolved fellow eyes included blood and urine cultures positive for CMV and lower CD8(+) T-lymphocyte count. CONCLUSIONS: Lesion characteristics can be used to predict advancement of preexisting disease, whereas only systemic factors are associated with development of bilateral disease. These analyses describe retinitis activity before the introduction of potent antiretroviral therapies but provide an important reference point for patients in whom CMV retinitis develops after failure or intolerance of antiretroviral agents. Arch Ophthalmol. 2000;118:1196-1204

Concurrent use of ganciclovir and foscarnet to treat cytomegalovirus infection in AIDS patients.

Ten patients with AIDS and progressive cytomegalovirus disease were treated with ganciclovir and foscarnet concurrently. The patients had received ganciclovir and foscarnet monotherapy a median of 330 days before receiving combination therapy for a median of 80 days. Nine of the 10 patients responded to the combination. No electrolyte abnormalities were noted during combination therapy, but rates of neutropenia (relative rate, combination vs. ganciclovir, 1.99; P = .229) and thrombocytopenia (relative rate, combination vs. ganciclovir, 1.53; P = .616) were higher with combination therapy than with either drug alone. The relative rate of anemia was significantly increased with combination therapy compared with monotherapy (relative rate, combination vs. ganciclovir, 2.69; P = .025). These data suggest that combination ganciclovir and foscarnet therapy after failure of either alone appears to be as effective as standard therapy with single agents. The rate of anemia with combination therapy was significantly greater than either agent alone, but no significant difference was noted among the other parameters of toxicity studied.

Dietary fructose or starch: effects on copper, zinc, iron, manganese, calcium, and magnesium balances in humans.

A balance study was conducted to assess the effects of consuming low-copper diets, high in fructose or cornstarch. The study involved 19 apparently healthy males, aged 21-57 y. The two experimental diets averaged 0.35 mg Cu/1000 kcal and provided 20% of the calories from fructose or cornstarch. Cu, zinc, calcium, magnesium, and iron balances were determined 1 wk before the study (pretest) when the subjects consumed self-selected diets and after consuming the experimental diets for 6 wk. No major differences in mineral balances were evident between the two groups during the pretest study when the subjects ate self-selected diets. In contrast, when fed the test diets, the group consuming the low-Cu fructose diet had significantly more positive balances for all minerals studied than the group fed the low-Cu cornstarch diet. The results indicate that dietary fructose enhances mineral balance.

Indices of copper status in humans consuming a typical American diet containing either fructose or starch.

Twenty-four male subjects originally participated in a study to determine the effects of feeding diets comparatively low in copper (1.03 mg/day/2850 kcal) and containing either 20% fructose or starch on indices of copper status. During the course of feeding the diets for 11 wk, four of the subjects exhibited heart-related abnormalities and were removed from the study. Fructose ingestion had no effect on serum ceruloplasmin activity or serum copper concentration but did significantly reduce cuprozinc superoxide dismutase (SOD) activity of erythrocytes as compared to starch. Repletion of the subjects with 3 mg copper/day for 3 wk significantly increased SOD levels in subjects previously fed fructose but not starch. Apparent copper balance was significantly greater when the subjects consumed the fructose as compared to the starch diet. These results suggest that the type of dietary carbohydrate fed can differentially affect indices of copper status in humans.

Analysis and evaluation of zinc and copper in human plasma and serum.

Recommendations for daily dietary intakes of copper and zinc have been made by the National Academy of Sciences during the last decade. As a result there is increasing interest in analytic techniques for accurate and precise assessment of these trace elements in human tissues, including blood. In addition, the importance of standardizing techniques for the collection, preparation, and analysis of biologic samples is now recognized. The necessity for preventing contamination or losses requires careful monitoring at each step, from collection to analysis. Likewise, precision and accuracy must be established for techniques and certified reference standards employed. The selection of an ideal anticoagulant for preparing plasma for copper and zinc analyses is receiving increased attention. The discrepancy observed regarding higher concentrations (10-15%) of zinc and copper in serum than citrated plasma remains to be resolved. Following analysis and summary of the data, interpretation of the results is of paramount importance. It must be remembered that abnormal plasma or serum zinc or copper concentrations do not necessarily reflect true aberrations in metabolism, since several conditions (disease and nondisease) can also influence these indices of trace element nutriture. Immediate attention must be given to advancing the concept that trace element analysis of biological materials requires special collection, storage, and analysis precautions.

Correlations of changes in dietary potassium and sodium with blood pressure during a one-year study.

Twenty eight adults, 12 men and 16 women, participated in a 1-yr study designed to assess accurately daily nutrient intake. All subjects lived at home, consumed self-chosen diets, and maintained a detailed daily dietary record throughout the year. Four times during the year blood pressure was measured. Mean daily sodium and potassium intake was calculated for each subject for the 7-day period before blood pressure measurements. Dietary intakes averaged 3.9 and 2.6 g/day of sodium and 3.3 and 2.2 g/day of potassium for men and women, respectively. Mean blood pressures for the four measurements were 120 mm Hg (systolic) and 77 mm Hg (diastolic) for men and 110 mm Hg (systolic) and 70 mm Hg (diastolic) for women. There were no significant correlations between absolute sodium or potassium intake and blood pressure. However, an individual's variability about his own mean potassium intake was significantly negatively correlated to the variability about his own mean systolic pressure in the male subjects (r = -0.43, p less than 0.002). There was no similar correlation in the female subjects. Changes in sodium intake were not associated with changes in blood pressure in either the men or women.

Iron intake and status of men and women consuming self-selected diets.

Iron intakes and iron status (serum ferritin and iron balance) were determined in 16 women and 13 men consuming self-selected diets over a 1-yr period. Iron balance was determined during four 7-day balance periods corresponding to the four seasons of the year. The seasonal variation in iron intake and serum ferritin and the correlation among iron intake, iron balance, and serum ferritin was examined. No seasonal variation was found in iron intake or serum ferritin. No direct correlation could be found between iron status (ferritin levels and iron balance) and iron intake. However, the men who met or exceeded their recommended dietary allowance for iron intake had ferritin levels in a range indicative of adequate iron status. None of the women met their recommended dietary allowance and their ferritin levels indicated marginal iron stores.

Zinc, copper, and manganese intake and balance for adults consuming self-selected diets.

Twenty-eight adult men and women participated in a year-long study designed to determine accurately the nutrient intake of adults who lived at home and consumed self-selected diets. During four metabolic balance periods, 7 days each, corresponding to the seasons (spring, summer, fall, winter), duplicates of the diet, and all urine and feces were collected. Daily mean intakes for zinc and copper were 9.9 and 1.2 mg, respectively. These levels were less than the recommended daily intakes of 15 mg for zinc and 2 to 3 mg for copper. In contrast, the mean dietary intake of manganese was 3.0 mg/day which is within the suggested safe and adequate range of 2.5 to 5.0 mg. Metabolic balances were negative for all three elements possibly due to a reduction in food intake during the collection periods compared to the noncollection intervals. The collection of the duplicate diets apparently influenced the food intake during the collection weeks.

Sodium and potassium intake and balance in adults consuming self-selected diets.

Twenty eight adults, 12 men and 16 women, participated in a 1-yr study designed to assess daily nutrient intake accurately. All subjects lived at home, consumed self-chosen diets, and maintained a detailed daily dietary record throughout the year. During four 7-day balance studies, one in each season of the year, meals, beverages, urine, and feces were analyzed for sodium and potassium content by atomic absorption spectrometry. Total intakes averaged 3.4 g/day for sodium and 2.8 g/day for potassium. The Na:K ratio for all diets analyzed averaged 1.3. Nutrient densities of sodium and potassium were 1.8 and 1.5 g/1000 kcal, respectively. Apparent absorptions of sodium and potassium were 98 and 85%, respectively, and did not change significantly over the wide range of intakes. Average urinary excretions of sodium and potassium were 86 and 77% of total intake, respectively. Mean metabolic balances were positive for sodium, +0.47 g/day, and potassium, +0.28 g/day. The data of this study provide useful information concerning the dietary intakes, excretions, and balances of sodium and potassium for adults based on analytic determination.