Clinical,immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: an Italian multicenter study

A questionnaire-based retrospective clinical and immunological survey was conducted in 73 males with a definite diagnosis of X-linked agammaglobulinemia based on BTK sequence analysis. Forty-four were sporadic and 29 familial cases. At December 2000, the patients' ages ranged from 2 to 33 years; mean age at diagnosis and mean duration of follow-up were 3.5 and 10 years respectively. After the mid-1980s all but 2 were on intravenous immunoglobulin (IVIG) substitution therapy, with residual IgG >500 mg/dl in 94% of the patients at the time of enrollment. Respiratory infections were the most frequent manifestation both prior to diagnosis and over follow-up. Chronic lung disease (CLD) was present in 24 patients, in 15 already at diagnosis and in 9 more by 2000. The cumulative risk to present at diagnosis with CLD increased from 0.17 to 0.40 and 0.78 when the diagnosis was made at the ages of 5, 10, and 15 years respectively. For the 9 patients who developed CLD during follow-up, the duration of follow-up, rather than age at diagnosis; previous administration of intramuscular immunoglobulin; and residual IgG levels had a significant effect on the development of CLD. Chronic sinusitis was present in 35 patients (48%), in 15 already at diagnosis and in 20 by 2000. Sistemic infections such as sepsis and meningitis/meningoencephalitis decreased over follow-up, probably due to optimal protection provided by high circulating IgG levels reached with IVIG.     

Quality control guidelines for testing gram-negative control strains with polymyxin B and colistin (polymyxin E) by standardized methods

An eight-laboratory study addressed the urgent need for quality control (QC) ranges for susceptibility determination when testing colistin (polymyxin E) and polymyxin B, two polycationic peptide antimicrobial agents, against multidrug-resistant gram-negative bacilli. For Escherichia coli ATCC 25922l, the QC ranges were as follows: for colistin, 0.25 to 1 microg/ml (11 to 17 mm), and for polymyxin B, 0.25 to 2 microg/ml (13 to 19 mm). For Pseudomonas aeruginosa ATCC 27853, the QC ranges were as follows: for colistin, 0.25 to 2 microg/ml (11 to 17 mm), and for polymyxin B, 0.25 to 2 mug/ml (14 to 18 mm). More than 97% of all reported QC results were within these proposed ranges.     

A reevaluation of the duration of survival after the onset of dementia

BACKGROUND: Dementia shortens life expectancy; estimates of median survival after the onset of dementia have ranged from 5 to 9.3 years. Previous studies of people with existing dementia, however, may have underestimated the deleterious effects of dementia on survival by failing to consider persons with rapidly progressive illness who died before they could be included in a study (referred to as length bias). METHODS: We used data from the Canadian Study of Health and Aging to estimate survival from the onset of symptoms of dementia; the estimate was adjusted for length bias. A random sample of 10,263 subjects 65 years old or older from throughout Canada was screened for cognitive impairment. For those with dementia, we ascertained the date of onset and conducted follow-up for five years. RESULTS: We analyzed data on 821 subjects, of whom 396 had probable Alzheimer's disease, 252 had possible Alzheimer's disease, and 173 had vascular dementia. For the group as a whole, the unadjusted median survival was 6.6 years (95 percent confidence interval, 6.2 to 7.1). After adjustment for length bias, the estimated median survival was 3.3 years (95 percent confidence interval, 2.7 to 4.0). The median survival was 3.1 years for subjects with probable Alzheimer's disease, 3.5 years for subjects with possible Alzheimer's disease, and 3.3 years for subjects with vascular dementia. CONCLUSIONS: Median survival after the onset of dementia is much shorter than has previously been estimated.     

Incidence of and risk factors for lipoatrophy (abnormal fat loss) in ambulatory HIV-1-infected patients

To identify clinical factors associated with the incidence of HIV-1-associated lipoatrophy, HIV-1-infected patients in the HIV Outpatient Study (HOPS) were prospectively evaluated for clinical signs of lipoatrophy at two visits about 21 months apart. Development of lipoatrophy was analyzed in stratified and multivariate analyses for its relationship to immunologic, virologic, clinical, and drug treatment information for each patient. Of 337 patients with no lipoatrophy at Survey 1, 44 (13.1%) developed moderate or severe lipoatrophy between the two surveys. In multivariate analyses, significant risk factors for incident lipoatrophy were white race (OR = 5.2; 95% CI: 1.9-17.1; =.003), CD4 T-lymphocyte count at Survey 2 less than 100 cells/mm3 (OR = 4.2; 95% CI: 1.3-13.1; =.013), and body mass index (BMI) less than 24 kg/m2 (OR = 2.4; 95% CI: 1.1-5.4; =.024). Analyses that controlled for the severity of HIV illness demonstrated no significant association with use of or time on any antiretroviral agent or class of agents and the development of lipoatrophy. Some host factors and factors associated with previous or current severity of HIV infection, especially CD4 T-lymphocyte cell count, appeared to have the strongest association with incidence of lipoatrophy.     

Hormonal contraception without estrogens

The long-term clinical effects of ethinyl estradiol and the impact on environmental safety of the alkylated estrogen components used in combined contraceptive pills remain the subject of debate. The development of improved methods for the use of progestogen-only contraception would represent a viable and desirable option. Several progestogen compounds are not alkylated, and these can be delivered through a variety of routes. Some of the progestogen-only methods are well established in clinical use. Estimates for both perfect and typical effectiveness are less than one pregnancy per 100 woman-years with oral, injectable, implantable and intrauterine methods. In practice, with the oral progestogen-only method, perfect and typical effectiveness range from three to five pregnancies per 100 woman-years. The main side effect with all progestogen-only methods is unpredictable vaginal bleeding during the first months of use, and this may lead to discontinuation. Nevertheless, continuation of use is more frequent if patients are well informed of this side effect before treatment begins. No cardiovascular- and cancer-related side effects have been proven.     

Onset of action of pimecrolimus cream 1% in the treatment of atopic eczema in infants

BACKGROUND: Data on the efficacy of pimecrolimus cream 1% within the first days of treatment are scarce, as in previous studies, the first postbaseline assessment was performed only after 1 week. OBJECTIVE: We sought to investigate the onset of action of pimecrolimus cream 1% in infants with mild to very severe atopic eczema. METHODS: We used pimecrolimus cream 1% (n = 129) or vehicle cream (n = 66) administered in a double-blind manner for 4 weeks and then open-label pimecrolimus cream 1% for 12 weeks, with a 4-week follow-up period. RESULTS: Pimecrolimus cream 1% reduced the mean Eczema Area and Severity Index at 4 weeks by 71.5% compared with an increase of 19.4% with vehicle ( P < .001). The reduction in the Eczema Area and Severity Index with pimecrolimus cream 1% was significant at day 4 (38.5% vs 17.6% increase with vehicle). Significant improvements in caregivers' assessments of pruritus and sleep loss were observed with pimecrolimus cream 1% by day 2 ( P < .03) and day 3 ( P = .002), respectively, compared with vehicle. Responses to pimecrolimus cream 1% were sustained during the open-label phase, and pimecrolimus cream 1% was well tolerated. Symptoms of atopic eczema returned gradually after discontinuation. CONCLUSION: Pimecrolimus cream 1% was well tolerated and effective in patients with mild to very severe atopic eczema, with rapid onset of action and no disease rebound after discontinuation.