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PubMedDate not supplied

A longitudinal study of lean and fat areas at the arm.

Using biceps and triceps skinfolds and upper arm circumference, areas of fat and lean tissue at the arm can be approximately determined based on a cylindrical assumption. Based on the first Zürich growth study a longitudinal analysis of estimated fat and lean areas is undertaken. Area may often be a more meaningful parameter than width in development, due to the increasing width of the limbs stretching the layer of fat. When comparing these quantities with the body mass index, correlations in boys were higher for lean area than for fat area, and about equally high for both measures in girls (around 0.8 beyond age 10). The primary goal of this investigation was to quantify the development of lean and fat arm areas from birth to adulthood, and to assess sex differences in this respect. The comparison with results obtained earlier from radiographic data is of particular interest, since such data can rarely be obtained any more, and overall this comparison can be considered encouraging. Lean area develops slowly until the onset of puberty, girls showing a slightly smaller value than boys. The pubertal spurt is very impressive in boys and moderate in girls, timed to age of peak height velocity in both sexes. Fat area changes only minimally in boys older than 16 months, and increases steadily in girls until age 16. The respective velocity curve shows a systematic up and down until age 5, when a gradual increase to a prepubertal fat spurt starts. It is interrupted by a trough in velocity--much more accentuated in boys--at puberty, and followed by a postpubertal fat spurt. When studying subgroups of subjects with a relatively high or relatively low adult body mass index, the heavy group differed relatively more in terms of fat area than lean area. Girls heavy as adults increase their fat area consistently more from about 5 years onwards. Boys later heavy show a qualitatively different pattern in puberty, with accentuated pre- and postpubertal fat spurts, but also a strong trough to a negative velocity in between.

Adipose Tissue↗

PubMed2005

Metabolic effects associated with atypical antipsychotic treatment in the developmentally disabled.

OBJECTIVE: Atypical antipsychotics, especially clozapine and olanzapine, have been increasingly associated with weight gain and other adverse metabolic events (diabetes mellitus, hyperlipidemia) in non-mentally retarded populations. This report explores the incidence of this phenomenon in an institution-dwelling population of individuals with developmental disabilities. METHOD: A retrospective longitudinal analysis was performed for a sample of 41 adults with developmental disabilities and comorbid psychiatric and/or behavioral syndromes for whom treatment was converted from typical antipsychotics to olanzapine or risperidone for a minimum period of 2 years. Data were collected from October 1998 to September 2002. Among parameters analyzed were chlorpromazine equivalent dosage of antipsychotic, metabolic parameters, body mass index (BMI), level of concurrent medications, and concomitant dietary restrictions. RESULTS: Thirty-two study subjects (78.0%) were men. The mean age of the study subjects was 43.6 years (at the end of the study). Thirty-seven (90.2%) had severe-to-profound mental retardation. Eight (19.5%) were on a restricted diet. Twenty-three subjects (56.1%) were switched from a typical antipsychotic to olanzapine, and 18 subjects (43.9%) were switched from a typical antipsychotic to risperidone. Of the subsample of subjects who were switched from a typical antipsychotic to risperidone, 12 (66.7%) went on to be switched to olanzapine because of either emergent side effects or lack of efficacy. For the overall sample (N = 41), there was a 19.3% increase in chlorpromazine-equivalent antipsychotic dosage from baseline to the 2-year endpoint along with a 5.6% decrease in fasting blood glucose from baseline to the 2-year endpoint. There were no significant differences between baseline and endpoint values for BMI, total cholesterol, low-density lipoprotein cholesterol, or triglycerides. CONCLUSION: The findings of this 2-year evaluation suggest that clinically or statistically significant BMI increases as well as blood glucose and lipid elevations are not unavoidably correlated with the use of the atypical antipsychotic agents olanzapine and risperi-done and may be minimized by careful monitoring, a regimen of dietary control, and a moderate activity level in a residential population of individuals with mental retardation.

Adult↗

PubMed2007

Temporal changes in sebum excretion and propionibacterial colonization in preadolescent children with and without acne.

BACKGROUND: It is generally accepted that the onset of sebum secretion occurs before puberty in boys and girls as a result of increasing androgen output during the adrenarche. Propionibacteria are part of the commensal skin flora and, in adults, are found in highest numbers in sebum-rich areas of skin such as the face and upper trunk. Previous studies investigating the association between sebum output and propionibacterial population densities have been cross-sectional and have been carried out mainly in adults. OBJECTIVES: The purpose of this study was to examine the association between the onset of sebum secretion and expansion of the propionibacterial flora in a population of early adolescent children aged between 5.5 and 12 years, and to evaluate the temporal relation between the two factors longitudinally. In addition, the study aimed to evaluate the change with age in sebaceous gland activity and propionibacterial colonization on the skin and in the nares between children who developed acne and those who did not. METHODS: Biannual examinations of volunteers included age, pubertal (Tanner) stage, weight and height, lesion counting on the face, propionibacterial colonization on the skin surface and in the nares and sebum secretion. A longitudinal analysis based on all observations of each subject throughout the study was applied to examine the change of sebaceous gland activity and propionibacterial colonization with age and pubertal stage. A generalized estimating equation was used with a 0.05 level of significance. RESULTS: The commencement of sebum production was asynchronous, with only a small number of follicles initially starting to secrete sebum onto the skin surface. The number of secreting follicles and the area of sebum increased with age and pubertal stage (P < 0.0001, P < 0.05, respectively). Numbers of propionibacteria on the skin tended to increase after the age of 9 years, but not significantly so. In contrast, numbers of propionibacteria in the nares increased significantly with age (P < 0.0001) but not with pubertal maturation. Children who developed acne had higher sebum output and propionibacterial densities with increasing age than children who did not develop acne. This effect was significant for the increase of total sebum area with age in pubertal children (P = 0.0023), the increase in number of secreting follicles with age (P = 0.020) in prepubertal children, and the increase in propionibacteria densities in the nares with age (P = 0.0005) in pubertal children. Sebaceous gland activity and propionibacterial numbers on the skin surface remained unchanged with increasing age in children who did not develop acne. Propionibacterial population densities in the nares increased with age regardless of the development of acne. CONCLUSIONS: Onset of sebum secretion and consequently expansion of the propionibacterial skin flora occur earlier in children who develop acne than in children of the same age and pubertal status who do not develop acne. These observations suggest that postponing the onset of sebum production or the expansion of the propionibacterial skin flora until after puberty may represent ways of preventing the disease or minimizing its severity. Determinants of propionibacterial colonization on the skin and in the nares may be different.

Acne Vulgaris↗

PubMed2001

Non-linear development of postural control and strategy use in young children: a longitudinal study.

This longitudinal analysis confirmed a non-monotonic pattern of postural control development in children from age 5 to 8 years suggested by previous cross-sectional studies. Postural control was considered in terms of control strategy and its variability operationalized by mean and standard deviation of center of pressure (COP) velocity; and of effectiveness and its variability operationalized by mean and standard deviation of COP anteroposterior (a-p) excursion. Periods of significant variability were used to indicate behavioral transitions. Seventeen healthy children (nine males, eight females) aged 5-6 years (61.5-75 months) were tested at 3- to 4-month intervals up to age 8 years (83-97 months) in eyes-open quiet stance on a force platform for 30 s in each of ten trials. Data were reorganized into six developmental categories based on adjacent test dates prior to (-1) and after (+1, +2, +3, +4) a subject's trial with the lowest COP velocity (0). Developmental category is proposed to represent level of sensorimotor integrative skill. Within-subject ANCOVAs revealed a significant effect (P<0.0001) for developmental category with covariance due to height, weight and actual age removed. Post hoc tests showed a significant effect (P<0.0001) on measures of strategy. However, differences in COP velocity (type of strategy used) and differences in its variability (denoting a transition between strategies) were not always coincident. Performance outcome (COP a-p excursion) changed near linearly across categories. It was concluded that a non-monotonic change in control strategy as indicated by COP velocity describes the development of quiet stance equilibrium. A transition occurs from a primarily open-loop to incorporation of open- and closed-loop components of control. Honing of strategy used precedes and follows transitions. Constriction of velocity and excursion may typify the early stages of bimodal strategy. Developmental categories describe affiliation with the strategy employed and may represent differentiable levels of sensorimotor integrative skill. They may be more useful in assessing progression of equilibrium control than consecutive age in years.

Adaptation, Physiological↗

PubMed2004

Effect of vitamin D receptor and estrogen receptor gene polymorphism on the relationship between dietary calcium and bone mineral density in Japanese women.

In a longitudinal analysis of the results of bone mineral density (BMD) screenings conducted in local communities, we examined the effect of lifestyle improvements on BMD and investigated the influence of allelic variations of the vitamin D receptor ( VDR) and estrogen receptor ( ER) genes. The subjects were 484 women (age, 24-80 years) who underwent BMD screenings at least twice between 1994 and 2002. We conducted BMD measurements of the lumbar spine by dual-energy X-ray absorptiometry and performed a simple questionnaire survey of lifestyle factors. Women receiving pharmacotherapy, or those with bone fractures, were excluded, leaving 338 women eligible for the study. They were retrospectively divided into three groups: (i) premenopause, women who were at least 5 years preceding menopause; (ii) perimenopause, women who were within 5 years before or after menopause; and (iii) postmenopause, women who were at least 5 years past menopause. There was no correlation at all between improvements of lifestyle factors (i.e., calcium intake from dairy products and time spent walking) and fluctuations in lumbar-spine BMD after 1, 3, or 5 years in the pre-, peri-, and postmenopausal groups. For women in the postmenopausal group, the PP genotype for the ER gene correlated with a significantly higher initial BMD than those with the Pp and pp genotypes ( P = 0.04). After 3 years, presence of the TT genotype of Taq I of VDR gene polymorphism exhibited positive correlations ( r = 0.29, P = 0.03) with the improvements in calcium intake and in lumbar spine BMD for the perimenopausal group, whereas the Tt genotype showed negative correlations ( r = -0.48, P = 0.04). After 1, 3, and 5 years, presence of the Tt genotype showed a tendency toward a negative correlation with the increases in calcium intake and in lumbar spine BMD for the pre- and perimenopausal groups, although almost of these were not significantly different. In this study, we could not prove a positive correlation between the improvement of lifestyle and the fluctuation of BMD within a 5-year timeframe, although the polymorphisms within the VDR gene may have some influence.

Adult↗

PubMed2005

Predictors of hypertension and changes of blood pressure in HIV-infected patients.

OBJECTIVE: We assessed predictors of changes in systolic (SBP) and diastolic (DBP) blood pressure during follow-up and of the development of hypertension in HIV-infected individuals. METHODS: International cohort collaborative study (D:A:D) of established prospective cohorts of HIV-1-infected patients. Longitudinal analysis of changes in blood pressure (BP) was performed using mixed effects models in 17170 patients. Predictors of development of hypertension during follow-up (systolic BP > or =140 and/or diastolic BP > or =90 mmHg or initiation of antihypertensive treatment) were assessed using Cox models in 8 984 patients with a normal BP level at baseline. RESULTS: 73548 BP measurements with a median of 4 per patient (interquartile range [IQR]: 2-6) were recorded over a median follow-up of 2.3 years (IQR: 1.5-2.6). Risk factors significantly associated with a development of higher systolic BP and diastolic BP (differences > or =5 mmHg and P-values <0.001) during follow-up were: older age, male sex, higher body mass index (BMI) and use of BP-lowering drugs. In patients with normal BP at baseline, 1186 developed hypertension for an incidence of 72.1 per 1000 person-years (95% confidence interval: 68.2-76.0). Factors associated with development of hypertension were: male sex, higher BMI, older age, higher BP at baseline, high total cholesterol and clinical lipodystrophy. Cumulative duration of exposure to nucleoside reverse transcriptase inhibitors (P=0.75), protease inhibitors (P=0.92) as well as type of antiretroviral treatment at baseline (P=0.18) were not associated with a higher risk of hypertension. Cumulative duration of exposure to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was significantly associated with lower risk of hypertension (hazard ratio=0.78 and 0.67 for those treated < or =10 months and >10 months compared with no exposure; P=0.005). CONCLUSIONS: Increased blood pressure in HIV-infected individuals is associated with established risk factors for hypertension. There was no evidence for an independent deleterious effect of any class of antiretroviral drugs on BP, although the use of NNRTIs was associated with a lower risk of development of hypertension.

Adult↗

PubMed1992

Inocoterone and acne. The effect of a topical antiandrogen: results of a multicenter clinical trial.

BACKGROUND AND METHODS: Because acne is androgen dependent, antiandrogen therapy might improve the condition. Inocoterone acetate (RU 882) is a nonsteroidal antiandrogen that binds to the androgen receptor and has antiandrogenic activity in animal models. To test its topical effect on acne, 126 male subjects with facial acne completed a 16-week, multi-center, double-blind study in which the twice-daily application of a 10% solution of inocoterone was compared with vehicle solution. Baseline and monthly examinations included acne lesion counts and general and endocrine laboratory tests. RESULTS: Inflammatory papules and pustules showed greater reduction in the inocoterone-treated subjects than in the subjects treated with vehicle. This difference achieved statistical significance by week 12 (24% reduction vs 10%) and week 16 (26% reduction vs 13%) and, with longitudinal analysis, throughout the course of the study. Global assessments and changes in comedo counts and sebum excretion rates were not significantly different between the groups. No serious adverse reactions were encountered. CONCLUSIONS: In this double-blind study of 126 male subjects with acne, a topical solution of the antiandrogen inocoterone, compared with vehicle, produced a modest but statistically significant reduction in the number of inflammatory acne lesions.

Acne Vulgaris↗

PubMedDate not supplied

A randomized controlled trial of auricular acupuncture for cocaine dependence.

BACKGROUND: Partly because of a lack of a conventional, effective treatment for cocaine addiction, auricular acupuncture is used to treat this disorder in numerous drug treatment facilities across the country for both primary cocaine-dependent and opiate-dependent populations. OBJECTIVE: To evaluate the effectiveness of auricular acupuncture for the treatment of cocaine addiction. METHODS: Eighty-two cocaine-dependent, methadone-maintained patients were randomly assigned to 1 of 3 conditions: auricular acupuncture, a needle-insertion control condition, or a no-needle relaxation control. Treatment sessions were provided 5 times weekly for 8 weeks. The primary outcome was cocaine use assessed by 3-times-weekly urine toxicology screens. RESULTS: Longitudinal analysis of the urine data for the intent-to-treat sample showed that patients assigned to acupuncture were significantly more likely to provide cocaine-negative urine samples relative to both the relaxation control (odds ratio, 3.41; 95% confidence interval, 1.33-8.72; P =. 01) and the needle-insertion control (odds ratio, 2.40; 95% confidence interval, 1.00-5.75; P =.05). CONCLUSIONS: Findings from the current study suggest that acupuncture shows promise for the treatment of cocaine dependence. Further investigation of this treatment modality appears to be warranted.

Acupuncture Points↗

PubMed2001

Increase in weight in all birth cohorts in a general population: The Tromsø Study, 1974-1994.

BACKGROUND: Obesity is a risk factor for a number of chronic diseases. Few longitudinal studies have examined changes in body mass index (BMI [calculated as weight in kilograms divided by the square of the height in meters]). OBJECTIVE: To investigate the changes in mean BMI and the prevalence of obesity in a large cohort examined several times during a 20-year period. METHODS: Mean BMI, the percentage of subjects with low BMI (<20 kg/m(2)), and the percentage who were obese (BMI > or =30 kg/m(2)) were determined in a large population of men and women who were examined up to 4 times during a 20-year period (1974-1994/1995). In a longitudinal design, we observed 3541 men who attended all 4 screenings (1974-1994/1995) and 4993 women who attended the last 3 screenings (1979/1980-1994/1995). RESULTS: The age- (25-49 years) and sex-adjusted mean BMI increased 1 kg/m(2) in men from 1974 to 1994/1995 and 0.9 kg/m(2)in women from 1979/1980 to 1994/1995. In the last survey, subjects aged 25 to 85 years were included. In most age groups, the mean BMI exceeded 25 kg/m(2) and the prevalence of obesity was 10% or higher in men and women aged 45 years or older. In the longitudinal analysis, the mean BMI in men aged 20 to 49 years increased 2.0 kg/m(2) during 20 years of observation and increased 2.4 kg/m(2)in women aged 20 to 49 years during 15 years of observation. The increase in BMI was larger in younger men than in older men. CONCLUSIONS: Body mass index increased in every examined birth cohort (1925-1964) during the 15- to 20-year observation period. Primary prevention of further increased body weight should be a priority.

Adult↗

PubMed2002

Persistence and emergence of anemia in children during participation in the Special Supplemental Nutrition Program for Women, Infants, and Children.

CONTEXT: The prevalence of iron-deficiency anemia in children has decreased owing to the provision of iron-containing infant formula and cereal and food vouchers to children enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). OBJECTIVE: To determine the prevalence of anemia and changes in anemia status in children receiving WIC supplementation. DESIGN: Retrospective cross-sectional and longitudinal analysis of information on WIC participants. Two definitions of anemia were considered separately: Anemia1 and Anemia2, the latter using a more stringent definition of anemia to avoid misclassification. PARTICIPANTS: Consecutive cohort of 7053 infants and children aged 6 to 59 months. MAIN OUTCOME MEASURES: Prevalence of anemia by age and race or ethnicity and relationship between anemia and sex, birth weight, and weight-for-height z score. RESULTS: Infants aged 6 to 8 months were 3.3 times more likely to be anemic than children aged 36 to 59 months. There was no association between anemia and race, birth weight, sex, or weight-for-height z score. Anemia rates were approximately halved in the more stringently defined Anemia2 group. Among children seen for at least 3 visits (n = 2926), 8.5% developed anemia and 19.1% of initially anemic children remained anemic; an additional 6.6% developed anemia at a third visit after having had 2 normal hemoglobin measurements. CONCLUSIONS: Anemia was common in WIC participants, with infants at highest risk. The diagnosis of anemia in black children depends on the cutoff value used. Despite ongoing receipt of WIC benefits, many children develop anemia or remain anemic. Implementation of mandatory follow-up of all anemic infants by WIC or health care providers may be warranted.

Adult↗

PubMed2003

Developmental, audiological, and speech perception functioning in children after cochlear implant surgery.

OBJECTIVES: To examine changes in audiological, speech perception, and developmental functioning subsequent to cochlear implantation in children with severe to profound hearing impairment, and to identify factors related to those changes. DESIGN: Prospective, longitudinal analysis to compare functioning of pediatric patients who underwent cochlear implantation before and 1 year after surgery. SETTING: Outpatient pediatric cochlear implantation program in an academic institution (The Listening Center, The Johns Hopkins University School of Medicine, Baltimore, Md). Patients Forty consecutive pediatric patients between 1(1/2) and 9 years of age who received a cochlear implant between April 1, 1996, and August 31, 1998, and who also underwent psychological, audiological, and speech perception evaluations immediately before and 1 year after implantation. MAIN OUTCOME MEASURE: Scores on the Bayley Scales of Infant Development-Second Edition, Stanford-Binet Intelligence Scale-Fourth Edition, Developmental Profile II, Child Behavior Checklist, speech perception categories, and audiological pure-tone thresholds. RESULTS: Mean (SD) duration of hearing impairment was 37.78 (27.94) months, mean (SD) age at surgery was 50.72 (27.66) months. Significant improvements were found 1 year after surgery in audiological, speech perception, and developmental functioning, but not in nonverbal intelligence or behavior. Greater benefits in audiological and developmental functioning were associated with younger age (<48 months) at implantation. CONCLUSIONS: Patients showed significant improvement in audiological status, overall developmental functioning, and speech perception skills in a short time after surgery. Greatest improvement in speech perception was for children with the least initial impairment, and greatest developmental gains were associated with young age at implantation.

Age Factors↗

PubMed2005

Incidence of hepatitis A in the United States in the era of vaccination.

CONTEXT: In the United States, hepatitis A is a frequently reported vaccine-preventable disease. Vaccination has been recommended for persons at increased risk since 1996. In 1999, it was recommended that children living in 11 states with the highest incidence of hepatitis A be routinely vaccinated, and that children living in 6 additional states, with incidence above the national average, be considered for routine vaccination. OBJECTIVE: To assess impact of the current vaccination strategy by evaluating trends in reported cases of hepatitis A since implementation. DESIGN, SETTING, AND CASES: A longitudinal analysis of characteristics of cases of hepatitis A reported in the United States since 1990 to the National Notifiable Diseases Surveillance System. MAIN OUTCOME MEASURE: Incidence rates of reported cases of hepatitis A. Incidence rates in 2003 were compared with those for the prevaccination baseline period (1990-1997) overall and in the 17 states in which children should be routinely vaccinated or considered for routine vaccination (vaccinating states). Incidence rates in vaccinating states were also compared with those in the remaining states where there is no recommendation for statewide vaccination of children (nonvaccinating states). RESULTS: Between the baseline period (1990-1997) and 2003, overall hepatitis A rates declined 76% to 2.6 per 100,000, significantly lower than previous nadirs in 1983 (9.2/100,000) and 1992 (9.1/ 100,000). The rate in vaccinating states declined 88% to 2.5 per 100,000 compared with 53% elsewhere (to 2.7/100 000). In 2003, cases from vaccinating states accounted for 33% of the national total vs 65% during the baseline period. Declines were greater among children aged 2 to 18 years (87%) than among persons older than age 18 years (69%); the proportion of cases in children dropped from 35% to 19%. Since 2001, rates in adults have been higher than among children, with the highest rates now among men aged 25 through 39 years. CONCLUSIONS: Following implementation of routine hepatitis A vaccination of children, hepatitis A rates have declined to historic lows, accompanied by substantial changes in the epidemiologic profile. Greater decreases in the age groups and regions where routine vaccination of children is recommended likely reflect the results of implementation of this novel vaccination strategy. Continued monitoring is needed to verify that implementation continues to proceed and that low rates are sustained.

Adolescent↗

PubMed1999

Optimal volume of processed plasma and total number of selective plasmapheresis sessions in the treatment of patients with severe generalized myasthenia gravis.

The selection of the technical parameters of plasmapheresis in the treatment of patients with MG varies widely due to the lack of sufficient data from controlled studies to standardize the plasmapheresis procedure. Eight myasthenia gravis (MG) patients (Osserman IIb and III) received either immunoadsorption plasmapheresis (IA) with a IM-TR 350 (Asahi Medical Co., Tokyo, Japan) or double filtration plasmapheresis (DF) with a Cascadeflo AC-1770, with four in each group. A Plasmaflo AP 05 W (Asahi Medical Co., Tokyo, Japan) was used as the plasma separator in both groups. Each course of treatment consisted of five sessions of aphereses on alternate days. Plasma was sampled before and after passing through the column. Samples of plasma were analyzed for acetylcholine receptor antibody (AchRAb) at the start of plasmapheresis and sequentially after every 0.5 L of plasma treated. The IA method cleared significantly more AchRAb during the initial treatment of 1. 5 L of plasma than the DF method, especially in the initial 1 L (P < 0.01). The column saturated after treatment of 1.5 to 2 L of plasma. It is known that over-saturation of column may release the already adsorbed/filtrated antibodies. Longitudinal analysis on the serological changes during the five sessions revealed that the clearance obtained using the IA method was significantly higher and more sustained after the first session of treatment compared to the DF method (P < 0.05). The titers of AchRAb were also noted to rise after the fourth session. These results suggest that 2 L of processed volume is optimal in terms of the functional capacity of a plasmapheresis column in either IA or DF methods, and that a total of four sessions of treatment in one course may provide optimal elimination of AchRAb.

Adult↗

PubMed1997

Local cost sharing in Bamako Initiative systems in Benin and Guinea: assuring the financial viability of primary health care.

The fourth in a series of five, this article presents and analyses data on cost recovery and community cost-sharing, two key aspects of the Bamako Initiative which have been implemented in Benin and Guinea since 1986. The data come from approximately 400 health centres and result from the six-monthly monitoring sessions conducted from 1989 to 1993. Community involvement in the financing of local operating costs in the two national scale programmes is also described. In Benin and Guinea, a user fee system generates the community financed revenue with the aim of covering local operating costs including drugs. Health worker salaries remain the responsibility of the government and donor funding covers vaccine and investment costs. Village health committees manage and control resources and revenue. The community is also involved in decision making, strategy definition and quality control. In Benin in 1993, community financing revenue amounted to about US$0.6 per capita per year and generally covered all local recurrent non salary costs except vaccines and left a surplus. Although total costs and revenues were slightly lower in Guinea for the same period, over-all user fee revenue (around US$0.3 per capita per year) covered local recurrent costs (not including salaries or vaccines). A comparison of costs and revenue between regions and individual health centres revealed important differences in cost recovery ratios. In Benin, some centres recovered more than twice the local costs targeted for community financing. Twenty-five per cent of centres in Guinea did not manage to cover their designated local recurrent costs. The longitudinal analysis showed that the level of cost recovery remained stable over time even as preventive care (and especially EPI) coverage rose significantly. To better understand the most important characteristics affecting cost recovery levels, best performing health centres in terms of cost-recovery levels in 1993 were compared to worst performing centres. This analysis showed that the size of the target population of the health centre is a key determinant of cost-recovery in both countries. In addition, in Guinea the utilization of curative care linked to geographical access and in Benin the average revenue per case linked to the number of deliveries proved to be additional factors of importance. In best performing centres, financial viability improved over time in both countries between 1990 and 1993. Finally, the implications of these conclusions for the planning of health centre revitalization in West Africa are discussed.

Benin↗

PubMed1998

Progressive loss of IL-2-expandable HIV-1-specific cytotoxic T lymphocytes during asymptomatic HIV infection.

In HIV-1 infection, circulating HIV-1-specific cytotoxic T lymphocytes (CTL) exist in different states of activation, including activated cytotoxic cells and memory cells. We report that a subpopulation of HIV-1-specific CTL is capable of clonal expansion upon culture with IL-2 without exogenous antigen. The IL-2-expandable HIV-1-specific CTL precursor frequency was reduced in patients with advancing infection, although HIV-1-specific memory CTL could still be detected by stimulation in vitro with allele-specific HIV-1 peptide. Longitudinal analysis during advancing infection showed a progressive decline in the IL-2-expandable HIV-1-specific CTL precursor (CTLp) frequency without a decline in Epstein-Barr virus (EBV)-specific or allo-specific CTLp frequencies. To address mechanisms that may contribute to the decline in the IL-2-expandable HIV-specific CTL response, the requirements for in vitro generation of HIV-1-specific and EBV-specific effector CTL were examined. In the absence of exogenous IL-2 in limiting dilution, generation of EBV-specific CD8+ effector CTL was dependent upon help from CD4+ cells. CD4+ help for EBV-specific CD8+ CTL was observed in asymptomatic HIV infection but not in advanced infection. In the presence of exogenous IL-2, CD4+ cells could also provide help for the optimal generation of HIV-1 peptide-specific CD8+ CTL, because in vitro depletion of CD4+ cells prior to culture using stimulation with an MHC class I-restricted HIV-1 peptide reduced the peptide-specific CD8+ CTL response. We conclude that there is a decline in the IL-2-expandable HIV-1-specific CTL response during advancing infection. There are a number of possible mechanisms for this decline, including a reduction in CD4+ T cell help for in vivo antigen-activated CD8+ T cells.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Selective pressure exerted by immunodominant HIV-1-specific cytotoxic T lymphocyte responses during primary infection drives genetic variation restricted to the cognate epitope.

HIV-specific cytotoxic T lymphocytes (CTL) play a central role in the control of HIV-1 replication during primary infection. It has been hypothesized that the appearance of CTL escape mutants represents an important mechanism by which HIV-1 escapes the host cell-mediated immune response. However, evidences for a direct relationship between CTL responses and emergence of CTL escape mutants are still limited. Here we report detailed longitudinal analysis of DNA sequence variation performed over the entire HIV-1 envelope in two subjects during primary HIV infection. Estimates of the frequencies of synonymous (ds) and non-synonymous (dN) nucleotide substitutions were used to identify regions of the HIV-1 envelope which were subjected to significant levels of selective pressure. These regions were shown to comprise defined epitopes recognized by CTL. Furthermore, dN mutation fixed within these epitopes effectively abolished recognition by the host CTL response. These results provide compelling evidence that the CTL epitope mutations directly resulted from the selective pressure exerted by the virus-specific cytotoxic response.

Cells, Cultured↗

PubMed1989

Prognostic relevance of urinary neopterin in non-Hodgkin's lymphomas.

Neopterin excretion levels were assessed in 66 consecutive patients affected by non-Hodgkin's lymphomas (NHL). The logarithm of the mean value of the whole series was 2.71 (log [mumol neopterin/mol creatinine]), significantly higher (P less than 0.001) than the control value (2.12). Fifty-six of 66 patients had a raised excretion of neopterin in amounts statistically related to the stage of disease. The mean value (2.51) of patients in Stages I-II was lower than the mean value (2.86) of patients in Stage III-IV (P less than 0.001). The 2-year probability of survival was 64% for patients in Stages I-II and 34% for patients in Stages III-IV. However, patients with lower neopterin excretion (less than 2.65) fared better than patients with higher neopterin excretion, regardless of the stage. Longitudinal analysis showed a trend toward a correlation between response to therapy and neopterin excretion. In NHL, the raised neopterin excretion appears to be a consequence of activation of the host immune system rather than a product of the malignant cells. But this excessive activation of the monocytes-macrophages, as reflected by urinary neopterin levels, is not accompanied by a better outcome. In conclusion, although neopterin cannot be considered a typical tumor marker, nevertheless it is an useful prognostic marker in NHL.

Biopterins↗

PubMed2002

Effect of interferon-alpha therapy on epitope-specific cytotoxic T lymphocyte responses in hepatitis C virus-infected individuals.

The majority of hepatitis C virus (HCV)-infected individuals fail to resolve the infection and become chronically infected despite the presence of HCV-specific CTL responses directed to different HCV-derived peptide antigens. Only a minority of individuals is able to clear the virus by mounting efficient CTL responses early after acute infection, but at present it is not clear whether viral clearance is associated with CTL responses of defined specificity. To elucidate those responses associated with improvement of the disease, we analyzed CTL responses to 16 different HLA-A2-presented, HCV-derived epitopes in 12 chronically infected patients, 14 chronically infected patients treated with interferon-alpha, and in one patient with acute symptomatic disease. We show here that the majority of chronically infected individuals present CTL responses directed to an NS4-derived peptide antigen (amino acids 1789-1797). Treated patients presented stronger HCV-specific CTL responses and therapy-induced changes in CTL target choice. In particular, 13 out of 14 individuals responded to an NS3-derived epitope (amino acids 1073-1081). By longitudinal analysis we show that five individuals responding to IFN-alpha therapy with decreases in alanine aminotransferase levels presented a strong CTL activity directed to the NS3-derived epitope. One patient that spontaneously resolved the infection presented a generally strong CTL activity specific for HCV-derived epitopes with a dominant response to the NS3-derived peptide antigen. This suggests that CTL responses directed to this NS3-derived antigen may be beneficial for the control of HCV infection. Improvement of these responses may represent a therapeutic intervention in chronic HCV infection.

Adult↗