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Biochemical markers of bone metabolism in growing thoroughbreds: a longitudinal study.

This study describes longitudinal changes in serum levels of biochemical markers of bone cell activity in a group of 24 thoroughbred foals from birth to 18 months of age. The markers of bone formation included the type I collagen carboxy-terminal propeptide (PICP), the bone-specific isoenzyme of alkaline phosphatase (BAP), and osteocalcin (OC). Levels of the cross-linked telopeptide of type I collagen (ICTP), a marker of bone resorption, and the N-terminal propeptide of type III collagen (PNIIIP), a marker of soft tissue turnover, were also measured. Levels of all markers fell significantly between birth and 18 months of age (70-80 per cent); this decrease being most marked between 0 and 6 months. However, a transient increase in levels of the markers then occurred between 6 and 14 months of age. The timing of this increase was specific for each parameter. ICTP and OC concentrations increased between October and December. PICP concentrations increased between December and April whereas the increase in PIIINP was coincident with the peak in weight gain between April and June. Changes in BAP concentration were less distinct at this time. Season was shown to have significant effects on the biochemical markers independent from the effect of age. Concentrations of all markers decreased with increasing body weight and at any given age heavier horses had lower marker levels. These results show that biochemical markers of bone cell activity and soft tissue turnover follow characteristic patterns of change in growing thoroughbreds influenced by age, season and bodyweight. The demonstration that the reference ranges for the biochemical markers change from month to month means that single samples from individuals are of little value for monitoring bone cell activity in growing thoroughbreds.

Alkaline Phosphatase↗

A longitudinal study of maternal serum vascular endothelial growth factor in early pregnancy.

Using a competitive radioimmunoassay to measure total immunoreactive vascular endothelial growth factor (VEGF), we describe for the first time longitudinal changes in serum VEGF in early pregnancy. The measurements were obtained from 26 women following the transfer of cryopreserved embryos; 18 singleton and eight twin pregnancies were identified by ultrasound at 6 weeks gestation and subsequently delivered as live births. Subjects did not have corpora lutea and exogenous hormone support was provided for the first 70 days of pregnancy. Serum VEGF increased approximately 30 days after embryo transfer and thereafter continued to rise in both singleton and twin pregnancies over a period of 20-40 days after which concentrations remained elevated. The longitudinal profile of serum VEGF concentrations was characterized by a logistic curve for singleton and twin pregnancies; the profile of VEGF concentrations in the twin pregnancies was significantly higher than in the singleton pregnancies (P < 0.0001). Profiles of the longitudinal concentrations of serum human chorionic gonadotrophin (HCG), oestradiol and progesterone were created by polynomial regression for singleton and twin pregnancies. The VEGF profiles were positively correlated with the profiles of HCG (r = 0.44, P = 0.02) and oestradiol (r = 0.36, P = 0.07) but not progesterone (r = 0.16, P = 0.42). Serum VEGF concentrations in the singleton thawed embryo pregnancies were compared with gestation-matched normal singleton pregnancies with corpora lutea. Concentrations of VEGF were significantly (P = 0.004) greater in the pregnancies with corpora lutea although this difference became less marked with advancing gestation. In addition to its important role in angiogenesis, we speculate that VEGF is involved in mechanisms which control the maternal cardiovascular adaptation to pregnancy.

Chorionic Gonadotropin↗

Predictors of care dependency in Alzheimer's disease after a two-year period.

This paper presents the results from a panel study in the Netherlands of 68 female in-patients with Alzheimer's disease. The main focus of this study was to investigate longitudinal changes and differences in care dependency. Descriptive statistics indicated an increase in almost all 15 features of dependency in a two-year period. A stepwise regression procedure revealed that the loss of social relationships, the loss of the ability to communicate, and the degree of care dependency at entry to the study were the strongest predictors of the follow-up ratings. The pattern of findings reveals that the Care Dependency Scale is sensitive to care dependency increase after a two-year period, and that the scale has utility in establishing longitudinal patterns of care dependency.

Activities of Daily Living↗

Impact of chronic viral hepatitis on health-related quality of life in HIV: results from a nationally representative sample.

BACKGROUND: Little is known about the health burden of chronic viral hepatitis in HIV-infected patients. We compared health-related quality of life (HRQOL) of patients with HIV and hepatitis C virus (HCV) or HIV and hepatitis B virus (HBV) coinfection to those with HIV monoinfection. METHODS: Using a nationally representative sample of 1,874 adults with HIV who completed a baseline and two follow-up interviews, we identified those with HIV monoinfection (n = 1,493), HIV-HCV coinfection (n = 279), and HIV-HBV coinfection (n = 122). We measured baseline and change over time scores for physical and mental health (PHS, MHS), overall quality of life (QOL), overall health, and disability days. To identify the independent effect of coinfection, we adjusted for demographic and clinical predictors of HRQOL using multivariable regression. RESULTS: Despite significant differences in socio-demographic characteristics between groups, there were no differences in the baseline scores for PHS, MHS, overall QOL, overall health, or disability days between groups. The HRQOL did not decline significantly over time for the HIV patients with or without HCV or HBV coinfection. All groups reported similar longitudinal changes in the HRQOL scores for all measures. CONCLUSIONS: We found no significant differences in disease burden as assessed by a generic HRQOL instrument between patients with HIV monoinfection and HIV-HCV or HIV-HBV coinfection. These data are relevant in counseling coinfected patients regarding the impact of coinfection on HRQOL, and are important in designing clinical trials and conducting cost-effectiveness analyses including this vulnerable cohort.

Adolescent↗

Recovery of a partially damaged corticospinal tract in a patient with intracerebral hemorrhage: a diffusion tensor image study.

PURPOSE: We hypothesized that diffusion tensor imaging (DTI) could be useful for exploring corticospinal tract (CST) regeneration if longitudinal changes of diffusion anisotropy can be detected. In this study, we explored the recovery of a CST partially damaged by intracerebral hematoma in a patient by DTI. METHODS: A 61-year-old female patient and six age-matched control subjects were evaluated. The patient presented with complete paralysis of the left extremities, which occurred at the onset of a spontaneous intracerebral hemorrhage (ICH) in the right corona radiata and internal capsule. Over the five-month period following onset, motor function of the affected extremities slowly recovered to the normal range. Two longitudinal DTIs were acquired from the patient (at 3 weeks and 5 months from onset) and one DTI from the control subjects. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured using a region of interest (ROI) method. RESULTS: On the 3-week DTI, FA values of ROIs in the ICH regions in the affected hemisphere were significantly lower, and ADC values of ROIs in the same areas were significantly higher than those of the control subjects (p<0.002). However, both mean FA and ADC values of the affected hemisphere in the 5-month DTI showed no significant differences versus those of the control.

Aged↗

The Marks Asthma Quality of Life Questionnaire: further validation and examination of responsiveness to change.

We performed analyses to examine the structure, validity, and responsiveness to change of the Marks Asthma Quality of Life Questionnaire (AQLQ), originally validated in Australia in a self-administered format, among 539 U.S. subjects with asthma. Subjects were interviewed twice by telephone over an 18-month period. Based on factor analyses, the subscale structure of the AQLQ was modified slightly to eliminate item overlap among subscale scores. Cross-sectionally, total AQLQ scores were significantly correlated in expected directions with baseline asthma severity scores (r = 0.58), SF-36 physical (r = -0.66) and mental (r = -0.40) health status scores, and pulmonary function (FEV1% predicted, r = -0.14). Longitudinally, changes in AQLQ total and subscale scores were significantly (P<0.01) associated with changes in asthma severity and both physical and mental status. The AQLQ, administered by telephone, appears to be useful for assessing changes in the impact of adult asthma.

Adult↗

Major depression, adjustment disorders, and post-traumatic stress disorder in terminally ill cancer patients: associated and predictive factors.

PURPOSE: Few studies have been conducted to elucidate the psychological distress of terminally ill cancer patients. This study attempted to determine the prevalence of adjustment disorders (AD), major depression (MD), and post-traumatic stress disorder (PTSD) among terminally ill cancer patients, to identify factors that contribute to them, and to determine how they change longitudinally. PATIENTS AND METHODS: Consecutive terminally ill cancer patients were recruited. Patients were assessed for psychiatric disorders by structured clinical interview twice: once at the time of their registration with a palliative care unit (baseline), and again at the time of their palliative care unit admission (follow-up). Possible contributed biomedical and psychosocial factors were evaluated. RESULTS: The proportions of patients diagnosed with AD, MD, and PTSD at baseline (n = 209) were 16.3%, 6.7%, and 0% respectively, whereas at follow-up (n = 85), 10.6% were diagnosed with AD and 11.8% with MD. Lower performance status, concern about being a burden to others, and lower satisfaction with social support were significantly associated with AD/MD at baseline. There were changes in the diagnosis of AD and MD in 30.6% of the patients. Only the Hospital Anxiety and Depression Scale at the baseline was significantly predictive of AD/MD at follow-up. CONCLUSION: The factors underlying psychological distress are multifactorial. Early intervention to treat subclinical anxiety and depression may prevent subsequent psychological distress.

Adult↗

A multicenter evaluation of new treatment efficacy instruments for Alzheimer's disease clinical trials: overview and general results. The Alzheimer's Disease Cooperative Study.

Evaluating treatment efficacy in Alzheimer's disease (AD) clinical trials requires optimal assessment methods to determine the extent and clinical meaningfulness of potential therapeutic effects of pharmacologic agents. Development of improved outcome measures for AD clinical trials is a major objective of the Alzheimer's Disease Cooperative Study (ADCS), an NIA-sponsored, multisite clinical trials consortium. The ADCS Instrument Development Project evaluated the sensitivity, reliability and validity of new or improved measures in each of five assessment domains: (a) cognition (immediate and delayed memory, praxis, attention, and executive function); (b) clinical global change; (c) activities of daily living; (d) behavioral symptoms (agitation and other noncognitive symptoms); and (e) cognition in severely impaired patients. A total of 306 English-speaking subjects were enrolled in the study, including AD patients stratified by disease severity and cognitively normal, age-matched elderly subjects. Half were retested at 1 month and 2 months after baseline, and all received 6- and 12-month follow-up assessments. Spanish versions of these new measures are currently being evaluated. The development of this multisite study, the common methods and procedures, and a detailed description of the cohort are provided in this overview article. This multisite project demonstrates the feasibility of a consortium approach to instrument development. We were able to develop new instruments and efficiently evaluate their reliability and sensitivity to longitudinal change by capitalizing on the experience and patient resources of the participating ADCS research sites.

Aged↗

Accessibility of alcohol-related attitudes: a cross-lag panel model with young adults.

BACKGROUND: In the alcohol literature, most cognition research has focused on alcohol expectancies. Overall scores on alcohol expectancy questionnaires predict longitudinal changes in drinking behavior. However, the association between expectancy subscale scores and drinking behavior is inconsistent and modest. Attitudinal information may vary in accessibility (i.e., the ease or speed with which attitudinal information is evaluated), and more accessible (i.e., faster) attitudinal evaluations may predict heavier alcohol consumption. An alternative hypothesis arising from response competition theory is that heavy drinkers will show slow attitudinal evaluations, given that heavy drinkers frequently show mixed, inconsistent, or opposing alcohol-related beliefs. In this study we examined the degree to which speed of processing of alcohol-related evaluative judgments longitudinally predicted alcohol consumption in university students. METHODS: Response latencies for alcohol- and non-alcohol-related attitudinal inquiries and measures of alcohol use were administered at two intervals 4 months apart. RESULTS: The key findings were that response times for tension reduction and cognitive impairment items at time 1 positively predicted alcohol consumption at time 2. These results held after we accounted for autocorrelation in drinking and individual variability in reactivity. CONCLUSION: For items relating to tension reduction, response times fit a response competition hypothesis better than the attitude accessibility hypothesis.

Adolescent↗

Abnormal hippocampal development in children with medulloblastoma treated with risk-adapted irradiation.

BACKGROUND AND PURPOSE: Children with medulloblastoma demonstrate post-treatment neurocognitive deficits in a number of areas, including memory performance. However, there is no definitive understanding of the neuropathology underlying these functional deficits. Previous literature has reported that hippocampal integrity is crucial to the acquisition of new episodic memories. Therefore, we hypothesized that longitudinal hippocampal volume measurements are abnormal in patients with medulloblastoma and thereby provide a possible substrate for explaining memory dysfunction. METHODS: Twenty-five pediatric patients underwent 159 serial MR imaging examinations (mean = six examinations per patient) for up to 5 years after irradiation and chemotherapy treatment for medulloblastoma. Right and left hippocampal volumes were obtained by manually tracing 1.5-mm contiguous coronal sections through the structure. Random coefficient models were used to examine longitudinal change in hippocampal volume as a function of time after diagnosis. RESULTS: Both right and left hippocampal volumes initially decreased after treatment. This abnormal volume pattern continued until approximately 2-3 years after diagnosis, when hippocampal volumes returned toward a normal positive growth pattern. Volume loss occurred predominately in the posterior regions. Female sex, low parental education, shunt placement, and positive seizure history all had a significant negative impact on hippocampal volume. CONCLUSION: Pediatric medulloblastoma survivors demonstrate an abnormal pattern of hippocampal volume development after treatment. Radiation dose mapping may expand our understanding of region-specific changes in hippocampal volume. Further exploration of the relationships between radiation therapy, memory dysfunction, and hippocampal pathology in this population is warranted.

Amnesia↗

Psychotropic drugs in breast milk: no evidence for adverse effects on prepulse modulation of startle reflex or on cognitive level in infants.

Reversals in modulation of the startle reflex probably reflect maturational processes in the central nervous system. This study has investigated the longitudinal changes in prepulse modulation of the blink reflex in three groups of individual infants: (a) breast-fed infants of mentally ill mothers who were prescribed selected psychotropic drugs, (b) bottle-fed infants of similarly ill and medicated mothers, and (c) breast-fed infants of healthy control mothers. The acoustic stimulation paradigm and neurophysiological methods were similar to those used in previous studies and, in addition, the infants' development was simultaneously assessed using the Bayley Scales of Infant Development. All the infants were found to be developing normally and across all three groups we observed a clear transition in prepulse modulation of the eye-blink reflex from small inhibition or facilitation in early infancy (1-4 months) to a robust facilitation in middle infancy (5-8 months). This reversal probably reflects the changing balance of developing neural function in normal infants. There were, therefore, no discernible effects in breast-fed infants of exposure to small doses of antidepressant or neuroleptic drugs.

Acoustic Stimulation↗

Mobilization of PCBs from blubber to blood in northern elephant seals (Mirounga angustirostris) during the post-weaning fast.

Northern elephant seals (Mirounga angustirostris) are characterized by extended fasting during which they rely entirely on their own body reserves. During fasts, lipids are mobilized from blubber to match the energy requirements of the animal. This transfer frees toxic fat-soluble pollutants into the blood circulation, which may exert adverse health effects, especially in young and developing animals. We investigated the dynamics of mobilization of polychlorinated biphenyls (PCBs) from the blubber of northern elephant seal pups during the post-weaning fast. Longitudinal samples of blubber and serum were collected from free-ranging animals throughout the fast at Año Nuevo, California. Blubber biopsies were separated into inner and outer layers. The PCB profiles of blubber and serum consisted mainly of penta- (PCB-101, -110, -118), hexa- (PCB-138, -153) and hepta- (PCB-180, -183, -187) chlorobiphenyls, which accounted for almost 90% of the total PCB burden. Total PCB concentrations in inner blubber increased significantly between early and late fasting (563.6+/-162.0 microg/kg lipids at early versus 911.6+/-513.1 microg/kg lipids at late fasting) whereas they remained fairly constant in outer blubber (572.6+/-134.8 microg/kg lipids at early versus 659.2+/-158.8 microg/kg lipids at late fasting). A corresponding rise of PCB concentrations was observed in serum during the second half of the fast (3.8+/-1.1 microg/l serum at early versus 7.2+/-0.9 microg/l at late fasting). The longitudinal changes in circulating total PCBs could not be explained by the changes in serum lipid fractions (cholesterol, phospholipids, triacylglycerols and free fatty acids). The increases in total PCB concentrations in inner blubber and serum were more pronounced in leaner animals, which suggests that they might be more at risk to potential toxic effects.

Adipose Tissue↗

Doppler fetal circulation in pregnancies complicated by pre-eclampsia or delivery of a small for gestational age baby: 2. Longitudinal analysis.

OBJECTIVE: To observe the longitudinal changes in growth, and associated Doppler measurements, of the fetal circulation in pregnancies with a normal outcome and those complicated by pre-eclampsia, birth of a small for gestational age baby, or a combination of these complications. METHODS: Two hundred and ninety-two women had serial ultrasound scans performed from the 24th week of pregnancy. Measurements obtained included: the abdominal circumference, umbilical artery pulsatility index, the middle cerebral artery pulsatility index and time-averaged velocity, and the thoracic aorta pulsatility index and time-averaged velocity. Outcome measures included the birth of a small for gestational age infant, pre-eclampsia or a combination of these complications. RESULTS: One hundred and sixty-seven pregnancies ended in the normal birth of an appropriately grown infant at term, while 105 had a complicated outcome. They were divided into three categories: preeclampsia only (i.e. with the birth of an appropriately grown fetus, n = 13); small for gestational age only with no evidence of pre-eclampsia, n = 55; and pre-eclampsia complicated by the birth of a small for gestational age infant, n = 37. The group with pre-eclampsia complicated by small for gestational age was closest in characteristics to true clinical intrauterine growth restriction. A reduction in the abdominal circumference mirrored a rise in the umbilical artery pulsatility index and preceded changes in the middle cerebral artery and thoracic aorta. The greatest degree of change in the fetal circulation was observed during the three weeks preceding delivery. Ratios of the values obtained from the fetal and umbilical circulation demonstrated the greatest deviation from normal. CONCLUSIONS: A reduction in fetal growth velocity preceded changes observed in the fetal circulation. Ratios of the fetal Doppler parameters provided the clearest evidence of deterioration in the fetal condition. The information provided may be of use in the diagnosis and management of the growth-restricted fetus.

Female↗

Longitudinal study of behaviour disorders in low birthweight infants.

AIM: To compare the prevalence of childhood and adolescent behavioural problems in low birthweight infants with matched controls. METHODS: A cohort study of a geographically defined population of survivors of </=1500 g birthweight born in 1980 and 1981 and age, sex, and school matched controls was undertaken. Children with a clinical disability were excluded. Data from Rutter questionnaires, completed by parents and teachers when the children were aged 8 and again at age 14 years, were assessed. RESULTS: From an initial 40 321 births in 1980-81 there were 399 of birthweight </=1500 g, of whom 219 survived to age 8. After exclusion of the 42 children with clinical disability, 177 cases comprised the sample. Of these, 10 (6%) refused or could not be contacted, leaving 167 cases for each of whom a matched control was obtained. At age 14 years, both parent and teacher questionnaires showed an increased prevalence of behavioural problems in cases compared with controls. The presence of a pervasive behavioural problem, when the responses of parents and teachers were concordant, was present in 9% of cases and 3% of controls. There were 132 pairs where the cases and controls were the same at ages 8 and 14 years and provided longitudinal data. The parental questionnaire showed there was a significant decrease in the prevalence of behavioural problems for cases and controls between the ages of 8 and 14 years. There was almost no longitudinal change in the prevalence of behavioural problems as shown by the teacher questionnaires. CONCLUSION: Although low birthweight infants are at increased risk of behavioural problems, because they comprise only a small proportion of all births, their population attributable risk for behavioural disorder is around 2-3%.

Adolescent↗

ADCS Prevention Instrument Project: overview and initial results.

One objective of the Alzheimer's Disease Cooperative Study (ADCS) is to develop new or improved instruments and assessment methods for evaluating treatment efficacy in Alzheimer disease (AD) clinical trials. The ADCS Instrument Committee has previously helped to define the state of the art in assessment for AD and Mild Cognitive Impairment clinical trials. We are now entering an exciting era of primary prevention trials to evaluate promising treatments that may delay disease onset and there is a need to develop appropriate instruments for these trials. The ADCS instrument committee has undertaken a project to develop instruments for prevention studies that assess domains known to be important in AD. Prevention trials are long and require large numbers of subjects, making them costly and requiring a high burden of participation for subjects. The current study focused on developing instruments that can be completed at home and in the clinic. The instruments are being evaluated in a cohort of nondemented elderly participating in a 4-year longitudinal study that simulates the design of a primary prevention trial. This report describes the design, baseline characteristics, and some longitudinal outcomes of the study cohort through the completion of the first 2 years of follow-up. We also describe the assessment domains to be measured with our new experimental instruments. This study recruited 644 subjects, 75 years of age and older. Participation in a "book club" that provided free books of interest to elders was offered as a recruitment incentive. Approximately 23% had some mild cognitive symptoms consistent with a Clinical Dementia Rating of 0.5. All subjects received a standardized in-clinic evaluation at baseline, which is repeated annually for 4 years to identify cases suspected of developing dementia and to measure longitudinal change on established clinical assessments. Subjects completed a set of self-administered experimental instruments at home or in the clinic designed to assess cognitive function and behavior, global change, activities of daily living, quality of life, and resource use. An additional "mail-in cognitive function questionnaire" was obtained separately by mail, 1 month before the other assessments. To evaluate the feasibility, efficiency, and validity of the home-based instruments in comparison with acquiring the same information during a clinic visit, subjects were randomized to 1 of 2 conditions in which the baseline and annual follow-up assessments are completed either at home ("home group") or at the study site during their clinic visits ("clinic group"). This initial report describes the ongoing 4-year longitudinal study and provides baseline results, which confirm the feasibility of obtaining home-based clinical information via mail or telephone. Initial results for the experimental instruments and for the book club are reported in separate accompanying articles.

Activities of Daily Living↗

Reliability of gas exchange measurements from two different spiroergometry systems.

Reliability of two different spiroergometric systems was investigated by comparing gas exchange measurements from two consecutive identical bicycle ergometer ramp exercise tests which were conducted after an initial habituation trial. Twenty-three healthy subjects (age: 25+/-5 years; weight: 71+/-10 kg; peak oxygen uptake: 55+/-9 ml x min(-1) x kg(-1)) took part in the study. One apparatus was a portable mixing chamber system (MetaMax I, Cortex, Leipzig, Germany), the other one a stationary spiroergometric device measuring in the breath-by-breath mode (MetaLyzer 3B, Cortex). There were no relevant systematic changes in gas exchange measurements and heart rate from test 1 to test 2. Intra-class reliability coefficients were 0.984 (oxygen uptake = VO2), 0.977 (carbon dioxide output = VCO2), and 0.973 (minute ventilation = VE) for the MetaMax I, and 0.969 (VO2), 0.964 (VCO2), and 0.953 (VE) for the MetaLyzer 3B. Bland-Altman plots revealed a slightly smaller variability of MetaLyzer 3B measurements compared to those of MetaMax I. It is concluded that the spiroergometric devices MetaMax I and MetaLyzer 3B represent reliable instruments for exercise testing in sports medical routine and research. This is important to decide if longitudinal changes in gas exchange measurements represent clinically meaningful differences in performance or merely inconsistencies of the measuring tool.

Adult↗

A comparative longitudinal quality of life study using the Spitzer quality of life index in a randomized multicenter phase III trial (FFCD 9102): chemoradiation followed by surgery compared with chemoradiation alone in locally advanced squamous resectable thoracic esophageal cancer.

BACKGROUND: The aim of the study was to compare the longitudinal quality of life (QoL) between chemoradiation with or without surgery in patients with locally advanced squamous resectable esophageal cancer included in a randomized multicenter phase III trial (FFCD 9102). MATERIALS AND METHODS: All patients with locally advanced resectable (T3-4 N0-1 M0) epidermoid or glandular esophageal cancer (n = 451) received induction chemoradiation. Responders (n = 259) were randomized between surgery (arm A) and continuation of chemoradiation (arm B). The Spitzer QoL Index was scored (0-10) at inclusion and at each follow-up, every 3 months during 2 years. QoL at baseline and longitudinal changes were respectively compared with univariate ANOVA and mixed-model analysis of variance for repeated measurements. The time interval between the follow-up was assessed and the same analyses were performed among survivors with 2 years of follow-up. RESULTS: The squamous histology was predominant in both arms. The mean QoL score decreased between baseline and the first follow-up and between the first and the second follow-ups. QoL scores at the first follow-up were comparatively worse in arm A than in arm B (7.52 versus 8.45, P < 0.01), whereas the longitudinal QoL study showed no difference between treatments (adjusted P = 0.26). Furthermore, the longitudinal QoL was not different (adjusted P = 0.23) among survivors with 2 years of follow-up. CONCLUSIONS: Among patients responding to induction chemoradiation, surgery and continuation of chemoradiation had the same impact on QoL in patients with locally advanced, resectable esophageal cancer although a significantly greater decrease in the Spitzer Index was observed in the postoperative period.

Adenocarcinoma↗

Effects of mitoxantrone on multiple sclerosis patients' lymphocyte subpopulations and production of immunoglobulin, TNF-alpha and IL-10.

We designed this longitudinal study to clarify the short- and long-term effects of mitoxantrone on the immune system in a subgroup of multiple sclerosis patients treated at our centre. After 14 days we found a highly significant sustained reduction of leucocytes, primarily affecting neutrophils and most lymphocyte subsets except for naive and activated T lymphocytes. The CD4/CD8 ratio and serum immmunoglobulin levels were not affected. Furthermore, whole blood-stimulated mononuclear cell IL-10 production showed a significant lower level 2 weeks treatment, whereas basal IL-10 as well as stimulated and basal TNF-alpha secretion showed no significant changes. Longitudinal data disclosed a persistent decrease of B lymphocytes, while secretion of immunoglobulins, IL-10, and TNF-alpha was not altered in the follow-up. In conclusion, we confirmed a selective short-term effect of mitoxantrone therapy on most lymphocyte subpopulations, but not on immunoglobulines or the pro- and anti-inflammatory cytokines TNF-alpha and IL-10, which do not serve as possible response markers.

Adult↗