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PubMed1997

Glomerulointerstitial interaction of adhesion molecules in IgA nephropathy and membranoproliferative glomerulonephritis.

The expression of two adhesion molecules, ICAM1 (CD54) and ICAM3 (CD50), infiltrating cells positive for their ligand, LFA1 (CD11a), and the markers of total leukocytes (CD45), T cells (CD3), granulocytes/monocytes (CD15), and macrophages (CD68) in renal interstitium were examined by an indirect immunoperoxidase method. The study was longitudinally performed on repeat renal biopsy specimens from 69 patients with two different proliferative glomerulonephritides: 43 with IgA nephropathy (IgAN) and 26 with membranoproliferative glomerulonephritis (MPGN). Interstitial ICAM1 (iICAM1) was mainly expressed on endothelium of peritubular venules and sometimes on tubular epithelium, and interstitial ICAM3 (iICAM3) on infiltrating immune cells. In IgAN, iICAM1 was significantly correlated with glomerular infiltration of LFA1+ cells (gLFA1) and CD68+ cells (gCD68) (r = 0.478/0.500; P < 0.0001) as well as CD3+ cells (gCD3) (r = 0.402; P < 0.002). In MPGN, iICAM1 was significantly correlated only with gCD68 (r = 0.382; P < 0.05). In both diseases, iICAM1 and iICAM3 were significantly correlated with interstitial infiltration of LFA1+ cells (iLFA1) and CD68+ cells (iCD68) (r = 0.616 to 0.815; P < 0.0001) and with interstitial infiltration of CD3+ cells (iCD3) (r = 0.474 to 0.816; P < 0.01). The iICAM3 was also significantly correlated with interstitial CD45+ cells (iCD45) (r = 0.672 in IgAN and 0.769 in MPGN; P < 0.00001). Interstitial infiltration of these immune cells was significantly correlated with the histologic parameters indicating renal injury, such as the index of glomerular lesion and the percent interstitial volume (r = 0.410 to 692; P < 0.05). Longitudinal analysis revealed that the parameters described above showed corresponding change with each other at the follow-up biopsy. These findings suggest that the glomeruler infiltration of T cells and macrophages influences the ICAM1/ICAM3 expression of the interstitial cells, especially In IgAN, and that ICAM1/LFA1 and ICAM3/LFA1 interactions contribute to the persistent infiltration of the interstitium by immune cells in both diseases.

Adolescent↗

PubMed1997

Postnatal NGF administration causes adult hyperalgesia and overreactivity to social stimuli but does not reverse capsaicin induced hypoalgesia.

The present longitudinal analysis was aimed at assessing (i) the effects of developmental capsaicin (CAPS) administration on nociceptive responsivity and on the response of adult mice to social stimuli; (ii) the action of NGF on the ontogeny of the same nociceptive response and social stimuli; (iii) whether capsaicin treatment could be reversed by subsequent treatment with NGF. CD-1 mouse pups were treated with either capsaicin (50 mg/kg, s.c.) or vehicle on postnatal days (PNDs) 5 and 8. Every other day from PND 9 to PND 21 the same pups received a daily injection of NGF (0.75 mg/kg, s.c.). During both the prepuberal stage (PNDs 14, 21, and 28) and adulthood, mice were repeatedly tested in a hot-plate apparatus (52 +/- 0.1 degrees C for 1 min). At adulthood they also underwent an aggressive behaviour test. NGF-treated mice showed a shorter latency to hindlimb licking response in the hot plate compared to both controls and NGF-CAPS groups. CAPS-treated subjects showed a long-lasting hypoalgesia at both prepuberal and adult stages that was not modified by subsequent NGF treatment. Finally, NGF-treated mice were more aggressive than both controls and CAPS-NGF animals.

Aggression↗

PubMed1983

Hypertension and stroke.

The longitudinal analysis of the adult population of Framingham, Massachusetts has clarified the pivotal role of hypertension in the epidemiology of stroke. Stroke incidence increases in men and women as arterial blood pressure, either systolic or diastolic, increases. Isolated systolic hypertension increases the risk of stroke in the elderly. Successful antihypertensive therapy decreases stroke incidence in asymptomatic persons, hypertensive patients with transient ischemic attacks and survivors of hypertensive stroke. A stepped care approach to antihypertensive therapy utilizing diuretic drugs, antiadrenergic agents and vasodilators is well tolerated in the vast majority of patients with established cerebrovascular disease. Agents with a propensity to cause orthostatic hypotension should be avoided. Reduction of blood pressure should be gradual with dose increments at intervals of 6 to 8 weeks. Mild hypertension may be left untreated during the acute phase of atherothrombotic brain infarction. A trial of blood pressure reduction with sodium nitroprusside to normotensive or mildly hypotensive levels is indicated in patients with acute intracranial hemorrhage. If neurologic deterioration occurs, the infusion rate of sodium nitroprusside can be reduced and blood pressure will rapidly rise. Successful management of hypertension has undoubtedly contributed to the decreasing death rate from stroke in the United States.

Adult↗

PubMed1991

Rotation affects apparent radiographic positioning of femoral components in total hip arthroplasty.

The authors have noted a change in the varus/valgus positioning of femoral components on anteroposterior (AP) radiographs that is dependent on limb rotation after total hip arthroplasty (THA). This effect, called pseudoposition, was demonstrated in six cadaver femurs implanted with an uncemented prosthesis that is noncanal-filling in the AP dimension. The distal tip of the prosthesis was positioned posteriorly in all specimens due to the bow of the femur. External rotation causes pseudovalgus positioning, and internal rotation causes pseudovarus positioning. Awareness of this phenomenon is important in the longitudinal analysis of femoral components after THA and emphasizes the need for standardized radiographic technique.

Femur↗

PubMed1998

Association of age-related mitochondrial abnormalities with skeletal muscle fiber atrophy.

The hypothesis that mitochondrial dysfunction contributes to the senescent loss of skeletal muscle was investigated in quadriceps from 2- to 39-year old rhesus monkeys. Histological approaches, both cross-sectional (a single cross-section of the muscle) and longitudinal (multiple cross-sections of individual fibers spanning a 350-1600 microm region), were used to identify muscle fibers with abnormal mitochondrial electron transport system (ETS) enzyme activities and mitochondrial DNA deletions. Fibers were examined for two ETS activities, succinate dehydrogenase (SDH, ETS complex II) and cytochrome c oxidase (COX, ETS complex IV). The number of individual fibers containing ETS abnormalities (predominately negative for cytochrome c oxidase activity and/or hyperreactive for succinate dehydrogenase) increased with age. Deletions of the mitochondrial genome were observed in 89% of these ETS abnormal fibers. Longitudinal analysis allowed characterization of the ETS abnormal phenotype along their length. A decrease in cross-sectional area in 14% of the ETS abnormal fibers supports the hypothesis that deleted mitochondrial genomes may contribute to age-related fiber atrophy.

Aging↗

PubMedDate not supplied

Prenatal cocaine exposure produces gender-specific motor effects in aged rats.

This investigation employed a longitudinal analysis of a complex motor skill in rats that were exposed prenatally to cocaine. Offspring were derived from four maternal treatment groups: 50 mg/kg cocaine, their pair-fed controls, 25 mg/kg cocaine, and freely fed controls. Cocaine was administered via gavage from gestation day 6-20. A maternal fostering procedure was used. Pairs of male and female littermates began training when 9, 13, or 19 months old. The behavioral procedure involved fixed-ratio (FR) lever pressing to obtain brief periods of wheel running. The oldest males from the 50 mg/kg, 25 mg/kg, and pair-fed groups performed significantly fewer wheel revolutions per opportunity than females or freely fed males. In general, animals earned fewer opportunities to run as the FR requirement was increased over sessions. However, within each age-by-gender group, subjects from the four treatment groups performed equivalent amounts of lever pressing. The specific effect on the motor aspect of the procedure may have resulted from a reduction of motor coordination, balance, or strength, or a diminished capacity of wheel running to serve as a reinforcing stimulus in a cocaine-sensitive subgroup.

Animals↗

PubMed2003

Exploring the relationship between women's health and the use of complementary and alternative medicine.

In this paper we identify the need for further research exploring the relationship between complementary and alternative medicine (CAM) use and women's health. We offer our personal thoughts on the direction such future research might take outlining a number of research domains (type of CAM consumption, longitudinal analysis of women's use of CAM, cross-cultural analysis of women's CAM consumption, reasons for women's CAM consumption). We hope that this brief paper helps inspire greater research attention upon what we believe to be a well deserving sub-field of study within the social science of CAM.

Australia↗

PubMed1998

Identifying the cause of left ventricular systolic dysfunction after coronary artery bypass surgery: the role of myocardial contrast echocardiography.

OBJECTIVE: Intraoperative myocardial contrast echocardiography was used to determine whether the identification of regional myocardial flow patterns during revascularization could predict myocardial contractile function immediately after separation from cardiopulmonary bypass (CPB) and at 1 month after coronary artery bypass grafting (CABG) surgery. DESIGN: A prospective, open-labeled, longitudinal analysis. SETTING: Two independent university hospitals. PARTICIPANTS: Twenty patients, during and up to 1 month after CABG. INTERVENTIONS: The contrast agent Albunex (Mallenckrodt Medical, Inc, St Louis, MO) was injected into the aortic root during CPB. MEASUREMENTS AND MAIN RESULTS: Myocardial contrast echocardiography opacification of flow was graded from intraoperative transesophageal echocardiographic images of the left ventricle in the short-axis, midpapillary view. The same myocardial images were also evaluated for regional wall motion abnormalities at 15, 30, and 60 minutes, 24 hours, 5 to 8 days, and 1 month after CPB. Logistic regression analysis was used to analyze the flow scores and regional function data from identical segments. Regional flow represented by contrast enhancement was assessed in 70% of the myocardial regions (55 of 80 possible segments; 95% confidence interval [CI], 61 to 76). Flow was more easily evaluated in the posterior region (95%) than in the anterior (70%) or septal regions (60%), and least likely evaluated in the lateral regions (50%). Regional wall motion was scored in 84% of the myocardial regions (469 of 560 possible regions). Function (segmental wall motion) was assessed in all regions with equal success. Segmental function and flow scores were matched to the same regions 66% of the time (53 of 80 possible series; 95% CI, 55 to 76). Regional myocardial contrast flow patterns did not predict myocardial function at 15, 30, or 60 minutes after separation from CPB. However, contrast opacification of flow did predict regional myocardial function at 1 week (p < or = 0.05) and at 1 month (p < or = 0.01) after CABG surgery. The probability that myocardial function would be normal at 1 month was 0.62 when intraoperative flow opacification was abnormal and 0.98 when flow opacification was normal. For patients with normal flow, the estimated odds of having normal myocardial function were 3.33 times those of patients with abnormal flow at 1 week (odds ratio, 3.33; 95% CI, 1.09 to 10.19) and 18.5 times those of patients with abnormal flow at 1 month (95% CI, 2.44 to 140.48). CONCLUSION: Intraoperative application of myocardial contrast echocardiography to determine regional flow patterns after revascularization may help differentiate conditions of left ventricular systolic dysfunction immediately after separation from CPB for CABG surgery and appear to predict myocardial function at 1 month.

Adult↗

PubMed1999

A clonal Plasmodium falciparum population in an isolated outbreak of malaria in the Republic of Cabo Verde.

We present the first parasitological, molecular and longitudinal analysis of an isolated outbreak of malaria. This outbreak occurred on Santiago Island (Republic of Cabo Verde), a region where malaria is hypoendemic and controlled, and thus the population is considered non-immune. Blood samples were collected from the inhabitants over 1 month and during cross-sectional surveys in the following year. The presence and nature of the parasites was determined by PCR. Plasmodium falciparum was the only species detected. Genetic analysis revealed that the circulating parasites were genetically homogeneous, and probably clonal. Gametocytes were found throughout this period. Our data suggest that this represented a focal outbreak, resulting in the infection of at least 40% of the villagers with a clonal parasite line. Thus, P. falciparum infections can persist for at least 1 year in a substantial proportion (10%) of the hosts. Implications for malaria control and the interpretation of epidemiological data are discussed.

Africa, Western↗

PubMed2004

Depressive disorder as a long-term antecedent risk factor for incident back pain: a 13-year follow-up study from the Baltimore Epidemiological Catchment Area sample.

BACKGROUND: The co-occurrence of affective distress and back pain is well documented but the relationship between them is less certain. This study examines the relationship between lifetime occurrence of depressive disorder and incident back pain reported over a 13-year period. METHOD: The Baltimore Epidemiologic Catchment Area Study is a prospective study of a household-residing cohort, selected probabilistically from East Baltimore in 1981. Between 1982-3 (wave 2) and again between 1993-6 (wave 3), a follow-up study of the original cohort was conducted. Questions on depressive disorder and back pain were drawn from the Diagnostic Interview Schedule. Logistic regression analyses were used to evaluate whether depressive disorder acts as a risk factor for incident back pain. RESULTS: In cross-sectional analyses, lifetime occurrence of depressive disorder was a significant correlate of lifetime prevalence of back pain at wave 1 (OR = 1.6, P = 0.01). During the 13-year follow-up, across three data collection points, there was an increase in the risk for incident back pain when depressive disorder was present at baseline (OR = 1.9, 95% CI 1.03, 3.4). However, during the short-term follow-up period of 1 year, between baseline and wave 2, depressive disorder at baseline was unrelated to first-ever reports of back pain. Lifetime depressive disorder in both waves 1 (baseline) and 2 (1 year later) was associated with a more than three times greater risk for a first-ever report of back pain during the 12 to 13 year follow-up period, in comparison to those who did not have depressive disorder at waves 1 or 2 (OR = 3.4, 95% CI 1.4, 7.8). Back pain at wave 1 was not significantly associated with an increased risk for depression in the longitudinal analysis (OR = 0.8, 95% CI 0.5, 1.4). CONCLUSIONS: Depressive disorder appears to be a risk factor for incident back pain independent of other characteristics often associated with back pain. Back pain is not a short-term consequence of depressive disorder but emerges over periods longer than 1 year. Moreover, in this study the alternative pathway of back pain as a risk factor for depressive disorder could not be supported.

Back Pain↗

PubMed2025

Multicompartment Quantitative Proteomics Revealing Potential Mechanisms Underlying the Treatment Effects of Mesenchymal-Derived Extracellular Vesicles in a Monkey Model of Cortical Injury.

Previous studies have demonstrated that mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) enhance functional recovery after cortical injury in rhesus monkeys by reducing chronic microglial inflammation, neuronal damage, and myelination deficits. However, the signaling pathways underlying these therapeutic effects remain largely unexplored. In this study, employing a reliable quantitative proteomics platform UHR-IonStar, we identified the protein cargo of MSC-EVs infused intravenously to rhesus monkeys 24 h and 2 weeks post-injury to the motor cortex. We then analyzed global protein expression changes across cerebrospinal fluid (CSF), plasma, and brain tissue of MSC-EV-treated versus vehicle-treated female, aged rhesus monkeys. A total of 1241/431/4124 monkey proteins were reliably quantified in CSF/plasma/tissue samples, respectively. Longitudinal analysis of CSF and plasma samples highlighted a shift from MSC-EV modulation of inflammatory and metabolic proteins in plasma at early recovery (2 weeks), toward modulation of plasticity-related proteins in CSF and brain tissue at later stages (4 weeks). Further protein-protein interaction analysis identified potential MSC-EV targets related to complementary signaling, proteolysis, and aminoglycan stability, which aligned with our previous findings. This comprehensive, multicompartment monkey proteomics study advances understanding of MSC-EV contents and treatment effects, paving the way for novel treatment of cortical injury.

Animals↗

PubMed2003

HBcAg-specific CD8 T cells play an important role in virus suppression, and acute flare-up is associated with the expansion of activated memory T cells.

We analyzed the prevalence and longitudinal fluctuation of hepatitis B virus (HBV)-specific CD8 T cells in chronic HBV infection using an HLA-A2-HBc18-27 tetramer. Thirty-five HLA-A2-positive patients with chronic HBV infection were divided into 17 HBe antigen (HBeAg)-positive and 18 anti-HBe antibody (anti-HBe)-positive patients. Five HLA-A2-positive normal subjects, five HLA-A2-negative patients with chronic HBV infection, and two HLA-A2-positive patients with acute HBV infection were included as controls. HBc18-27-specific CD8 T cells (c18-27-CD8Ts) were detected at a significantly higher prevalence in patients with anti-HBe (6/18) than in those with HBeAg (1/17), and their frequency reached 0.28% of the total CD8 T cells. The prevalence was significantly higher in patients with HBV DNA below 4.0 log genome equivalents (LGE)/ml (5/12) than in those with HBV DNA above 4.0 LGE/ml (2/23). The frequency of c18-27-CD8Ts was consistently higher in liver-infiltrating lymphocytes, ranging from 0.18 to 1.28%, than in autologous peripheral blood lymphocytes. Longitudinal analysis of patients with acute flare-up demonstrated that the elevation of alanine aminotransferase (ALT) was intimately associated with the expansion of c18-27-CD8Ts. Phenotypic analysis revealed that most c18-27-CD8Ts during acute flare-up expressed HLA-DR and CCR5, while those during low-ALT periods showed low expression. Furthermore, most liver-infiltrating c18-27-CD8Ts were positive for HLA-DR and CCR5, suggesting selective recruitment of activated c18-27-CD8Ts into the liver. In conclusion. HBV-specific CD8 T cells play an important role in the suppression of virus replication, and acute flare-up is associated with the expansion and activation of HBV-specific memory cells.

Adult↗

PubMed2002

The link between allergic rhinitis and allergic asthma: a prospective population-based study. The Copenhagen Allergy Study.

BACKGROUND: It has been hypothesized that allergic rhinitis and allergic asthma are manifestations of the same disease entity. We aimed to investigate the relationship between allergic rhinitis and allergic asthma. METHODS: Participants in a population-based study of 15-69-year-olds in 1990 were invited to a follow-up in 1998. A total of 734 subjects were examined on two occasions eight years apart. Allergic rhinitis to pollen was defined as a history of nasal symptoms on exposure to pollens and IgE specific to pollen. Allergic asthma to pollen was defined as a history of lower airway symptoms on exposure to pollens and IgE specific to pollen. Similarly, diagnoses of allergic rhinitis and allergic asthma to animals or mite were defined. RESULTS: At follow-up, all subjects with allergic asthma to pollen (n = 52) had in addition allergic rhinitis to pollen. In the longitudinal analysis, there were a total of 28 new (incident) cases of allergic asthma to pollen. They all had allergic rhinitis to pollen at baseline, or had developed allergic rhinitis to pollen at follow-up. Accordingly, allergic rhinitis to animals and mite were ubiquitous in subjects with allergic asthma to animals and mite, respectively. CONCLUSIONS: The results support the hypothesis that allergic rhinitis and allergic asthma are manifestations of the same disease entity.

Adolescent↗

PubMed2000

Evidence for a genetic etiology of early-onset delinquency.

Age at onset of antisocial behavior discriminates persistent and transitory offenders. The authors proposed that early-onset delinquency has an underlying genetic influence that manifests in problems related to inhibition, whereas late-onset delinquency is more environmentally mediated. To test these notions, they selected 36 early starters, 86 late starters, and 25 nondelinquent controls from a large sample of 11-year-old twins and compared them on several measures related to inhibition and a peer group measure. As expected, early starters had more psychological, behavioral, and emotional problems related to inhibition than late starters and controls. A longitudinal analysis indicated an increase an antisocial behavior among peers of late starters shortly before their delinquency onset. Family history data and a twin analysis provided evidence of greater genetic influence on early-onset than late-onset delinquency.

Adolescent↗

PubMed2005

Trauma, depression, coping, and mental health service seeking among impoverished women.

The authors examined the relationship among trauma, coping, depression, and mental health service seeking in a probability sample of sheltered homeless and low-income housed women. Results highlight the diversity of trauma. In a longitudinal analysis, women who lived in shelters or experienced major violence had a twofold increase in their risk of depression over the 6-month follow-up. In a cross-sectional analysis, childhood sexual abuse, living in a shelter, physical violence, childhood physical abuse, and death or injury of a friend or relative predicted avoidant coping and symptoms of depression. Active coping and depression predicted mental health service seeking among traumatized women. Modifying coping strategies may ameliorate some of the negative impact of trauma and potentially enhance mental health service use among at-risk women.

Adaptation, Psychological↗

PubMed1983

The use of serum deoxythymidine kinase as a prognostic marker, and in the monitoring of patients with non-Hodgkin's lymphoma.

A recently developed enzyme assay, utilizing [125I]-iododeoxyuridine as substrate, and capable of detecting normal levels of serum deoxythymidine kinase (s-dTk), was used in an investigation of sera from 155 untreated patients with non-Hodgkin's lymphoma (NHL). The patients were classified at the discovery of disease, both according to spread (stages I-IV according to the Ann Arbor classification) and to tumour histology (the Kiel classification). The results showed a significant correlation between s-dTk level and the extent of disease, as well as to the malignancy; i.e. the more advanced the disease or the more aggressive the tumour, the higher the s-dTk values. Greater than 100-fold increases in s-dTk levels were found in some patients compared to those reported for healthy individuals. A high pretreatment level of s-dTk for patients in stages III-IV correlated with a poor prognosis for the patient in terms of survival. This was consistent even when only patients in stages III-IV with "high-grade" malignant lymphomas were included in the analysis. Longitudinal studies of s-dTk levels in 19 NHL patients showed that s-dTk increases with progression of the disease, decreases during successful therapy, and finally increases during relapse. It is concluded that s-dTk could be used both as a prognostic marker and to monitor the effect of therapy in NHL patients.

Adolescent↗

PubMed2026

The contribution of common and rare genetic variation to emotional and behavioural symptoms in childhood and adolescence.

Genetic factors influence vulnerability to common mental health conditions, but their role in early-life mental health remains understudied. We analysed genotype array (n = 4709-6687) and exome sequence data (n = 4500-5424) from the Millennium Cohort Study (MCS) and Avon Longitudinal Study of Parents and Children (ALSPAC) to assess the contribution of common variants and rare deleterious coding variants to internalising and externalising symptoms across development. In longitudinal analysis spanning ages 5-17 years, we identified several associations between common genetic variation, indexed by polygenic indices (PGIs), and both symptom domains that generally remained stable across development. Effect sizes were modest, with the largest estimates observed for PGIs for attention deficit hyperactivity disorder (ADHD) and externalising behaviour with externalising symptoms (β = 0.13-0.18; p-adj<3.5×10⁻29). Evidence for direct genetic effects was strongest for externalising symptoms, including for associations with the ADHD and externalising behaviour PGIs. Concordant results were observed in the Born in Bradford cohort. A higher exome-wide burden of deleterious rare variants was associated with increased externalising and internalising symptoms (β = 0.04-0.06, p-adj<0.03); within-family models indicated direct genetic effects on externalising in MCS (β = 0.07; p < 0.05, p-adj>0.05) and on internalising symptoms in ALSPAC (β = 0.12, p-adj<0.02). Common and rare genetic variants contributed independently, jointly explaining 2% of the variance in internalising and 5-7% in externalising symptoms. This study shows that early-life mental health is influenced by both common and rare genetic variation, with several associations explained by direct genetic effects.

Journal Article↗

PubMed2025

Biomarkers of inflammation in sweat after myocardial infarction.

ST-elevation myocardial infarction (STEMI) triggers a significant inflammatory response. Sweat may offer a novel, non-invasive medium for monitoring inflammation. In this prospective study, we characterized the inflammatory signatures in plasma and sweat collected from the skin surface of two patient groups: (1) 18 STEMI patients immediately following percutaneous coronary intervention (exposure) and (2) six patients who underwent outpatient angiography without subsequent intervention (control). Levels of 92 biomarkers were measured using a high-throughput proteomic assay and reassessed after 4-6 weeks in STEMI patients. Adjusting for patient group, sweat biomarkers did not show significant changes over time. In plasma, hepatocyte growth factor and interleukin-6 showed a significant decrease from the acute phase to follow-up, adjusted for patient group. STAM binding protein was significantly higher in the sweat of STEMI patients compared to controls, adjusted for time effects. While sweat was less sensitive than plasma for detecting biomarker levels in the setting of STEMI, its longitudinal analysis via wearable sensors holds promise for detecting specific markers.Trial registration: The trial is registered on www.clinicaltrials.gov with the trial registration number NCT05843006.

Aged↗