Methotrexate in the management of severe steroid dependent asthma

AIMS: This study was designed to assess the efficacy of low dose methotrexate, 15 mg weekly, as a steroid-sparing agent in asthmatic patients requiring long-term oral prednisone treatment. METHODS: The study was a randomised, double blind, placebo controlled, cross over study of 48 weeks duration. Eleven patients with severe steroid-dependent asthma were included. A successful outcome was defined as a reduction in mean prednisone requirements of 7 mg daily compared to baseline requirements, during active treatment. RESULTS: Two patients were required to be withdrawn owing to methotrexate-related adverse effects. The mean prednisone dose for patients who completed the study was 14.4 mg per day (95% CI; 13.6, 15.1) during active treatment, and 12.9 mg per day (95% CI: 12.2, 13.6) during placebo treatment (NS). Only one patient reduced his individual dose requirements by more than 7 mg per day, whereas in three patients prednisone requirements actually increased during active treatment. There were no significant differences in symptom scores, pulmonary function data, and exacerbations between active and placebo treatments. CONCLUSION: No significant steroid-sparing effect was obtained using low dose methotrexate in this study. This negative outcome may be attributable to the small population of patients studied, low baseline FEV1, and the omission of a steroid minimisation run-in period. Our results highlight the importance of careful patient selection and a painstaking approach in the management of patients with steroid-dependent asthma.     

Cigarette smoking and submaximal exercise test duration in a biracial population of young adults: the CARDIA study

Symptom-limited, graded exercise treadmill testing was performed by 4,968 white and black adults, ages 18-30 yr, during the baseline examination for the Coronary Artery Risk Development in Young Adults (CARDIA) study. Compared with nonsmokers, the mean exercise test duration of smokers was 29-64 s shorter depending on race/gender group (all P < 0.001), but mean duration to heart rate 130 (beats.min-1) ranged from 20-50 s longer (P < 0.05). In each race/gender group, test duration to heart rates up to 150 was 15-35 s longer (P < 0.05) in smokers than in nonsmokers after adjustment for age, sum of skinfolds, hemoglobin, and physical activity score. The mean maximum heart rate was lower in smokers than in nonsmokers (difference ranging from 6.7 beats.min-1 in white men to 11.2 beats.min-1 lower in black women, P < 0.001), although maximum rating of perceived exertion was nearly identical in smokers and nonsmokers. Chronic smoking appears to blunt the heart rate response to exercise, so that exercise duration to submaximal heart rates is increased even though maximal performance is impaired. This may result from downloading of beta-receptors caused by smoking. Smoking status should be considered in the evaluation of physical fitness data utilizing submaximal test protocols, or else the fitness of smokers relative to nonsmokers is likely to be overestimated.     

Mechanical consequences of core drilling and bone-grafting on osteonecrosis of the femoral head

We employed an anatomically realistic three-dimensional finite-element model to explore several biomechanical variables involved in coring or bone-grafting of a segmentally necrotic femoral head. The mechanical efficacy of several variants of these procedures was indexed in terms of their alteration of the stress:strength ratio in at-risk necrotic cancellous bone. For coring alone, the associated structural compromise was generally modest, provided that the tract did not extend near the subchondral plate. Cortical bone-grafting was potentially of great structural benefit for femoral heads in which the graft penetrated deeply into the superocentral or lateral aspect of the lesion, ideally with abutment against the subchondral plate. By contrast, central or lateral grafts that stopped well short of the subchondral plate were contraindicated biomechanically because they caused marked elevations in stress on the necrotic cancellous bone. Calculated levels of stress were relatively insensitive to variations in the diameter of the graft.     

Low total serum cholesterol and intracerebral hemorrhagic stroke: is the association confined to elderly men? The Kaiser Permanente Medical Care Program

BACKGROUND AND PURPOSE: Epidemiological studies indicate a higher incidence of intracerebral (but not subarachnoid) hemorrhagic stroke among persons with low total serum cholesterol levels. This report further examines the prospective relationship of total serum cholesterol with subsequent intracerebral hemorrhage in a large, well-defined population. METHODS: The cohort included 61756 enrollees in a health plan from the San Francisco-Oakland metropolitan area (46% men, 63% white), aged 40 to 89 years and free of cardiovascular disease at baseline. Sixteen-year incidence of combined nonfatal and fatal intracerebral hemorrhagic stroke (International Classification of Diseases [ICD], 8th revision, code 431, or ICD, 9th revision, codes 431 and 432) was investigated in relation to serum cholesterol measured in multiphasic health checkups made in 1977 through 1985. Intracerebral hemorrhagic events were ascertained using hospital discharge records and as underlying cause of death by the California Mortality Linkage Information System. RESULTS: From 1978 through 1993 (average of 10.7 years), there were 386 events (201 in men, 29% fatal; 185 in women, 42% fatal). By multivariate proportional hazards life-table regression analysis, serum cholesterol level below the sex-specific 10th percentile (< 4.62 mmol/L [178 mg/dL] in men), compared with higher cholesterol level, was associated with a significantly increased risk of intracerebral hemorrhage in men aged 65 years or older (relative risk, 2.7; 95% confidence interval, 1.4 to 5.0). An excess risk was also observed among elderly women at the lowest cholesterol range, but a chance finding could not be ruled out. No relationship was seen among men or women aged 40 to 64, and no statistical interaction of low serum cholesterol with hypertension was found in either sex. CONCLUSIONS: In these data, the association between low serum cholesterol level and intracerebral hemorrhage was confined to elderly men.     

Giardiasis. Issues in diagnosis and management

Giardia lamblia is a frequent cause of diarrhea throughout the United States and the world. Advances in basic biology indicate that different strains of Giardia exist, that mammals can be infected with G. lamblia-type organisms, and that secretory IgA is important to host protection. Although water remains the most common mode of transmission of Giardia, there has been an increase in the number of person-to-person cases, especially related to children in day care, as well as an increase in food-borne cases. New antigen detection assays have improved the ability to diagnose Giardia in the stool and make it unlikely that duodenal sampling will be necessary. Metronidazole has become the drug of choice for most cases of giardiasis because of its efficacy, favorable tolerance, and availability. For pregnant women who require treatment, a non-absorbable aminoglycoside, paromomycin, may be tried first and metronidazole used if initial treatment fails.