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PubMed1996

Propentofylline improves regional cerebral glucose metabolism and neuropsychologic performance in vascular dementia.

In a double-blind, placebo-controlled trial in thirty patients with mild to moderate vascular dementia (VD) according to DSM-III-R criteria, the effects of the adenosine uptake blocker propentofylline (HWA 285) on regional cerebral glucose metabolism (rCMRGl) was studied using positron emission tomography of 2-[18F]fluoro-2-deoxy-D-glucose (FDG). 25 subjects completed the 3-months study. Propentofylline significantly improved relative rCMRGl in the motor cortex, while relative rCMRGl in the placebo treated group worsened significantly. Neuropsychologically, visual information processing was improved in the propentofylline group and we observed a trend towards a slowing of the progression of cognitive deterioration in patients with VD. The results of the longitudinal analysis showed further that neuropsychological and metabolic changes are closely related. These findings justify a large-scale clinical trial to prove therapeutic efficacy.

Aged↗
PubMed1985

Relationship of body temperature stability to mortality in aging mice.

An age-related decline in the capacity for thermoregulation among homeothermic animals has been observed frequently under conditions of extreme ambient temperatures. We investigated the temporal stability of the internal body temperature of 69 C57BL/6J mice from 25 months of age until death in a controlled, neutral thermal environment. Estimates of temporal variability were calculated over consecutive 1-month intervals using (colonic) body temperature data collected weekly. The results of this longitudinal analysis indicated that the regulation of body temperature, as measured by its temporal stability, became increasingly less precise with advancing age. Body temperature exhibited a significant decline as the animal approached death. Individual differences in body temperature and the temporal regulation of body temperature were significantly correlated with lifespan, although the direction of the relations were opposite. Body temperature correlated positively with lifespan, whereas the temporal stability of body temperature correlated negatively with lifespan. Thus, animals exhibiting higher body temperatures and greater temporal stability also tended to live longer than their cohorts.

Aging↗
PubMed1995

The click-evoked oto-acoustic emission, c-EOAE, in preterm-born infants in the post conceptional age range between 30 and 68 weeks.

Click-evoked otoacoustic emissions (cEOAEs) were repeatedly recorded in an operational sample of 144 very low birth weight (VLBW) infants. A subgroup of 22 was composed of all those babies in which at least 4 recordings were successfully done. The mean birth weight of this group was 1040 g, and the mean duration of assisted ventilation was 17 days. The OAE-recordings were done in the post conceptional age (PCA) range between 30 and 68 weeks. In relation to ear function screening it was shown that the EOAE was present in 95% of the ears at least once at any age, while it was present in all recordings in only 34%. From a longitudinal analysis of the recordings per infant it appeared that: (1) the OAE recorded was already present in one infant at the PCA of 29.4 weeks; (2) in most infants the level of the OAE varies strongly between recordings; (3) in each infant the OAE-level shows an increase with age, on average this growth amounts to 10 dB between the PCAs of 31 and 42 weeks; (4) there is no clearcut difference in the growth of high- and low-frequency components of the EOAE.

Acoustic Stimulation↗
PubMed1993

Natural history of the Naegeli-Franceschetti-Jadassohn syndrome and further delineation of its clinical manifestations.

BACKGROUND: The Naegeli-Franceschetti-Jadassohn (NFJ) syndrome is rare; only three families have been reported. OBJECTIVE: Our purpose was to determine the natural history of this ectodermal dysplasia and to delineate further its clinical manifestations. METHODS: We reexamined the original family with the NFJ syndrome 65 years after the first description. RESULTS: The pedigree includes 62 members with 14 affected patients. We examined the 10 living patients. Longitudinal analysis of the pedigree revealed that the reticulate pigmentation fades after puberty and may disappear completely in old age. Hypohidrosis, the main problem for the patients, remains constant. Teeth are always severely affected, leading to early total loss. All patients lack dermatoglyphics. Diffuse palmoplantar keratoderma may coexist with punctate keratoses that are sometimes accentuated in the creases or exhibit a linear pattern. Four patients had congenital malalignment of the great toenails, not described previously in association with the NFJ syndrome. CONCLUSION: The NFJ syndrome is an ectodermal dysplasia with numerous specific abnormalities.

Adult↗
PubMed1990

Major histocompatibility complex genes influence the outcome of HIV infection. Ancestral haplotypes with C4 null alleles explain diverse HLA associations.

Several alleles at multiple HLA loci have been found to be associated with infection with human immunodeficiency virus (HIV): HLA A1; B8, B35; Cw7, Cw4; DR1, DR3 and DQ1, are associated with particular disease manifestations and/or disease progression. Furthermore, in a pilot study we have shown an increase in the frequency of C4 null alleles and suggested that all the reported HLA alleles could reflect association with a limited number of ancestral haplotypes (AHs). On this occasion, we studied 122 Caucasoid patients classified according to Centers for Disease Control (CDC) criteria. The control group consisted of 67 seronegative homosexual or bisexual males at risk of developing HIV infection. C4 null alleles were unequivocally present in 58% of patients in CDC IV compared with 33% of the seronegative subjects (chi 2 = 5.65, p less than 0.05). Furthermore, C4 null alleles could be excluded in only 8% and 16% of CDC III and IV, respectively, but in 30% of the seronegative subjects. An increased frequency of three AHs largely accounted for the increases in C4 null and HLA alleles. To examine the role of specific AHs we undertook a longitudinal analysis of a subgroup of 26 patients who seroconverted under observation. Seventeen of these patients were followed for 32 to 63 months. All seven patients with the 8.1 AH (A1, CW7, B8, BfS, C4AQ0, C4B1, DR3, DQ2) developed low CD4 lymphocyte counts (less than 450 x 10(6)/l) compared with only 2 of 10 patients without this haplotype (p less than 0.002). All three deaths occurred in patients with the 8.1 AH. The acquired immunodeficiency syndrome developed in three further cases with either 8.1- or B35-bearing (35.x) haplotypes. Sequential CD4/8 ratios showed an early and progressive decline in individuals with 8.1 or 35.x. Since the 8.1 and 35.x AHs contain deletions of the central major histocompatibility complex (MHC) genes, we suggest that the genes affecting HIV infection and progression are within the central MHC region.

Alleles↗
PubMed1994

The 3-dimensional stability of maxillary osteotomies in cleft palate patients with residual alveolar clefts.

OBJECTIVES: To evaluate the stability of maxillary osteotomies in cleft palate patients using miniplate fixation. DESIGN: A prospective clinical study. SUBJECTS: 46 consecutive cleft palate patients with residual alveolar clefts and maxillary hypoplasia in one or more dimensions. These patients underwent standardised maxillary osteotomies and simultaneous bone grafting of the alveolar cleft over 44 months during 1988-1992. Titanium mini-plate fixation was used for the maxilla in all patients. Follow-up ranged from 6 to 51 months with a mean of 28 months. MAIN OUTCOME MEASURES: The 3-dimensional stability of maxillary osteotomies in cleft palate patients in the long term. RESULTS: In the unilateral clefts, relapse in the horizontal plane was 22% and in the vertical plane 22.5%; in bilateral clefts, the relapse was 17.5% and 7% respectively, with no statistically significant difference between the two groups. Longitudinal analysis of the repositioned maxilla over a 3-year period showed that most of the relapse occurred in the first 6 months and stabilised at 2 years postoperatively. Relapse in the transverse plane, based on analysis of the study models of 26 cases, ranged from 13.4% to 33.6%. A clockwise rotational relapse of the maxilla was noted in bilateral cases. Postoperative orthodontics compensated for the horizontal relapse by increasing incisor proclination to maintain positive overjet. There was no significant difference between the relapse of bimaxillary cases and that of maxillary osteotomies alone. CONCLUSION: The long-term 3-dimensional surgical stability, using miniplate fixation, has decreased the relapse of cleft maxillary osteotomies with simultaneous alveolar bone grafting to a level comparable to that of maxillary osteotomies in non-cleft patients.

Adult↗
PubMed1995

Induction of T-helper cell response to hepatitis B core antigen in chronic hepatitis B: a major factor in activation of the host immune response to the hepatitis B virus.

The T helper (Th) cell response to hepatitis B core antigen (HBcAg) was analyzed in 76 chronic hepatitis B virus (HBV) carriers with varying degrees of hepatic inflammation and HBV replication. Fifty-five patients had active viral replication, 28 with minimal histological changes and normal alanine transaminase (ALT) and 27 with active hepatic inflammation and elevated ALT. The remaining 21 chronic hepatitis B surface antigen (HBsAg) carriers had undetectable HBV replication, minimal histological activity, and normal ALT. In addition, 34 chronic HBV carriers were studied prospectively during treatment with alpha-interferon. The HBcAg-specific Th cell response was evaluated by a proliferative assay using 3H-thymidine uptake and gamma-interferon production by peripheral blood mononuclear cells. The proliferative response and gamma-interferon production of patients with active hepatic inflammation were significantly higher than in patients with minimal histological changes and in controls. In the longitudinal analysis during alpha-interferon treatment, 22 of 34 patients sustained an ALT flare accompanied by a parallel, significant Th cell response, which preceded or coincided with the ALT flare. The elevation in the Th cell response and the ALT flare were followed by a significant rise in the serum immunoglobulin (Ig) M anti-HBc index. Ten of twenty-two patients with an enhanced Th cell response and an ALT flare seroconverted after alpha-interferon treatment. The Th cell activity in the 10 responders rapidly subsided after hepatitis B e antigen (HBeAg) to anti-HBe seroconversion, whereas in the 12 nonresponders it remained elevated.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1995

The urine protein to creatinine ratio as a predictor of 24-hour urine protein excretion in type 1 diabetic patients with nephropathy. The Collaborative Study Group.

The purpose of this study was to determine the usefulness of a random urine specimen protein to creatinine (P/C) ratio in predicting 24-hour urine protein excretion (24 UP) in type 1 diabetic patients with overt nephropathy. Two hundred twenty-nine outpatient diabetic subjects enrolled in the Collaborative Study Group's multicenter clinical trial of "Angiotensin-Converting Enzyme Inhibition in Type 1 Diabetic Nephropathy" provided specimens for study, which encompassed a wide range of proteinuria (0.05 to 13.3 g/d). Twenty-four hour urine collections for total protein and creatinine (g/d) were obtained in the outpatient setting. This was followed shortly thereafter by an untimed single urine specimen for protein and creatinine (mg/dL). For longitudinal analysis, 33 patients provided two 24-hour urine collections with concomitant random urine specimens, separated by at least a 3-month period. Across the range of proteinuria that we studied, the log random urine P/C ratio correlated to log 24 UP (r = 0.90). The regression line was almost identical to the line of unity, which indicates that a patient's 24 U/P (in g/d) can be predicted directly from the random urine specimen P/C ratio (P/C = 24 UP in g/d). However, the standard deviations associated with these predictions were large, especially at the higher 24 UP values. Of the 33 patients who provided two time-separated specimens, the direction of change in P/C ratio was discordant with the direction of change in 24 UP in 14 of the 33 repeat specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Experimental approaches to the evaluation of alcohol abuse and dependence development.

In rats, a complex longitudinal analysis of alcohol intake behaviour and electrophysiological sleep pattern was performed during different periods of stable voluntary alcohol consumption. By the sleep pattern, the existence of alcohol abuse and dependence development could be confirmed. Acute ethanol withdrawal was shown to be the obligatory and necessary element in alcohol abuse and dependence evaluation. The proposed behavioural and sleep pattern models might be used in the search for anti-alcoholic drugs in combination with the study of alcoholic aging processes.

Alcohol Drinking↗
PubMed1989

Magnetic resonance imaging and peripheral blood abnormalities in experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) was induced in twelve cynomologous macaques (Macaca fascicularis) by sensitization to autologous myelin basic protein (BP) in complete Freund's adjuvant (CFA). The white blood cell (WBC) count, absolute number of lymphocytes and absolute numbers of CD4+ and CD8+ T-cell subsets were measured weekly. Using magnetic resonance imaging (MRI), the animals were monitored twice weekly for the development of central nervous system (CNS) lesions. Conventional spin-warp imaging was performed using a General Electric CSI-II NMR imager/spectrometer (2 Tesla magnet). CNS lesions were detected by MRI in all of the animals sensitized to myelin BP. Longitudinal analysis of their peripheral blood leukocytes revealed a progressive leukocytosis and lymphopenia, which always preceded the onset of clinical signs and almost always also preceded the formation of detectable CNS lesions. These results suggest that frequent analysis of T-cell subsets may provide a more accurate means of predicting episodes of disease activity than clinical or MRI evaluation.

Animals↗
PubMed1991

An overview of body weight of older persons, including the impact on mortality. The National Health and Nutrition Examination Survey I--Epidemiologic Follow-up Study.

The authors studied distributions of body weight for height, change in body weight with age, and the relationship between body mass index and mortality among participants in the Epidemiologic Follow-up Study of the first National Health and Nutrition Examination Survey (NHEFS) (n = 14,407), a cohort study based on an representative sample of the U.S. population. Percentiles of body weight for height according to age and sex are presented. Cross-sectional analyses of body weight suggest that mean body weight increases with age until late middle age, then plateaus and decreases for older aged persons. However, longitudinal analysis of change in weight with age shows that younger persons in the lower quintile at baseline tend to gain more than those in the higher quintile. Older persons in the higher quintile at baseline have the greatest average loss in weight. The relationship of body mass index to mortality is a U-shaped curve, with increased risks in the lowest and highest 15% of the distribution. Increased risk of mortality associated with the highest 15th percentile of the body mass index distribution, as well as the highest 15% of the joint distribution of body mass index and skinfold thickness, is statistically significant for white women. However, the risk diminishes when adjusted for the presence of disease and factors related to disease. More noteworthy is the fact that there is a statistically significant excess risk of mortality for both race and sex groups in the lowest 15% of the body mass index distribution after adjusting for smoking history, and presence of disease. Those in the lowest 15% of the joint body mass index and skinfold thickness distribution, were also at increased risk. Risk of mortality for both men and women who have lost 10% or more of their maximum lifetime weight within the last 10 years is statistically significant, even when controlling for current weight. This study has replicated previously reported relationships, while correcting for several methodological issues.

Aged↗
PubMed1995

Double mutations of the N-ras gene in a patient with acute myelomonocytic leukemia.

We report a patient with acute myelomonocytic leukemia (AMMoL) who showed two independent point mutations of the N-ras gene at codons 12 and 13. Longitudinal analysis revealed that one mutation at codon 13 was detectable throughout his disease course and the other at codon 12 emerged as a second mutation 14 months after the diagnosis was made, at the refractory stage. Cloning to vector and subsequent sequencing confirmed that these mutations occurred in different alleles. Chromosome findings showed a simple abnormal karyotype at presentation and further karyotypic aberrations during his disease course, concomitantly with the second mutation of the N-ras gene. These findings revealed a close relationship among the disease progression, karyotypic evolution and a newly-appearing N-ras mutation.

Aclarubicin↗
PubMed1991

Fifteen-year follow-up for double internal thoracic artery grafts.

The internal mammary artery (IMA) is the conduit of choice for myocardial revascularization. From 1972 to 1989, 586 patients received bilateral IMA and supplemental vein grafts. There were 506 men (86%) and 79 women (14%) with a mean age of 55.5 years (range 32-77 years). Unstable angina was present in 138 patients (24%), insulin-requiring diabetes mellitus in 83 (14%) and previous myocardial infarction (MI) in 25 (4%). Preoperative angiography demonstrated triple-vessel disease in 286 patients (49%) and double-vessel disease in the remaining 300 patients (51%). Left main coronary artery disease (stenosis greater than or equal to 50%) was present in 53 (9%). The mean left ventricular score was 7.4 with a range of 5 to 20. The mean number of grafts performed was 3.4 per patient. Hospital mortality was 3.6% (21 patients). Follow-up was done through direct patient contact, via the patient's physician or by telephone contact with the patient themselves or surviving family members. Follow-up was complete in 518 hospital survivors and ranged from 1 month to 17.5 years with a cumulative follow-up of 911 patient years. At 10 and 15 years, respectively, the actuarial freedom from MI was 78% and 72% and freedom from reoperation was 93% and 86%. Actuarial survival at 10 and 15 years was 85% and 70%, respectively. This longitudinal analysis demonstrates that bilateral IMA grafting has a low operative risk. The data suggest that utilization of two IMA grafts yield excellent freedom from recurrent symptoms and provides excellent long-term survival.

Actuarial Analysis↗
PubMed2006

Maternal smoking during late pregnancy and offspring smoking behaviour.

We explored the influence of maternal smoking during late pregnancy on the likelihood of smoking among offspring in adolescence and adulthood, using birth cohort data collected in the United Kingdom as part of the 1958 National Child Development Study. Longitudinal analysis indicated that maternal smoking during late pregnancy was associated with an increased likelihood of being a non-smoker at 16-year, 23-year and 33-year follow-up. This association differed between male and female offspring, with women showing no significant association and men showing an increased likelihood of being a non-smoker. There did not appear to be any association between maternal smoking during late pregnancy and cigarette consumption among offspring who reported smoking for either sex. These results are inconsistent with some previous reports that maternal smoking during pregnancy increases the likelihood of smoking among female offspring, although the observation of a moderating effect of sex on smoking behaviour is consistent with several previous reports. We discuss possible mechanisms for this association, and suggest factors that may account for the observed sex differences in this association, and the discrepancy between our results and some previous reports.

Adolescent↗
PubMed2005

[Octylcyanoacrylate (Dermabond) for skin closure at the time of head and neck surgery: a longitudinal prospective study].

OBJECTIVES: A prospective non-randomised evaluation of the octyl-2-cyanoacrylate (Dermabond) for skin closure in head and neck surgery. MATERIALS AND METHODS: An inception cohort of 52 patients managed by six otorhinolaryngologists head and neck surgeons at a single institution (university teaching and tertiary referral center) during the months of May-July 2004. The length of the skin incision varied from 3 to 30 cm (mean: 7 cm). Morbidity evaluation, longitudinal analysis of the evolution of the scar, and analysis of the degree of satisfaction. RESULTS: Postoperative death was not encountered. The overall morbidity rate was 3.8% (2/52). There was no instances of wound dehiscence's. A subcutaneous abscess was noted in one patient. From an aesthetic point of view, the scar appearance was considered to be slightly retracted during the first postoperative month and to be very good 2 to 4 months from initial surgery. Only one patient developed a minimal cheloid scar. Among the 47 patients who expressed an opinion postoperatively regarding the use of the octyl-2-cyanoacrylate (Dermabond) for skin closure, the degree of satisfaction was very high due to the ability to take an early shower (40 patients) followed by the lack of skin sutures (5 patients) and the lack of any allergic skin reaction (2 patients). CONCLUSION: At our department, the octyl-2-cyanoacrylate (Dermabond) for skin closure at the time of head and neck surgery is becoming more and more utilized due to the completion of a solid and aesthetic suture, the ability to take an early shower and the high degree of satisfaction expressed by the patients.

Adult↗
PubMed2005

Importance of moderate ischemic mitral regurgitation.

BACKGROUND: The importance of moderate ischemic mitral regurgitation in patients presenting for coronary artery bypass grafting (CABG) is controversial. Therefore, we tracked the course of unrepaired moderate ischemic mitral regurgitation after CABG surgery alone, identified factors associated with worsening postoperative ischemic mitral regurgitation, and assessed the impact of unrepaired moderate ischemic mitral regurgitation on survival. METHODS: From 1980 to 2000, 467 patients with moderate ischemic mitral regurgitation underwent CABG alone. The course of unrepaired mitral regurgitation was estimated by a longitudinal analysis of 267 follow-up echocardiograms from 156 patients. The survival impact of moderate ischemic mitral regurgitation was determined among propensity-matched patients with and without ischemic mitral regurgitation. RESULTS: Mitral regurgitation was dynamic early postoperatively. Immediately postoperatively, it was absent or mild in 73% and severe in 6%; by 6 weeks, these figures were 40% and 22%, respectively. The course of postoperative mitral regurgitation was not associated with the preoperative extent of coronary artery disease or left ventricular dysfunction. Five-year survival of matched bypass patients without ischemic mitral regurgitation was 85% compared with 73% for patients with moderate ischemic mitral regurgitation (p = 0.003). CONCLUSIONS: Moderate ischemic mitral regurgitation does not reliably resolve with CABG surgery alone and is associated with reduced survival. Therefore, a mitral valve procedure may be warranted for such patients presenting for CABG. A randomized trial comparing strategies of revascularization with mitral valve repair and revascularization alone is required to determine optimal treatment.

Adult↗
PubMed2005

Comparison of saphenous vein and internal thoracic artery graft patency by coronary system.

BACKGROUND: We sought to compare saphenous vein and internal thoracic artery graft patency by coronary system. METHODS: From 1972 to 1999, 50,278 patients underwent primary coronary surgery; subsequently, 4,333 had angiography of 2,121 internal thoracic artery and 8,733 saphenous vein grafts. Longitudinal analysis was used to model graft occlusion and identify risk factors. Using the model, patency was calculated twice for each graft and compared first as if an internal thoracic artery, and second as if a saphenous vein, were used. RESULTS: Unadjusted 1-, 5-, and 10-year patency was 93%, 88%, and 90% for internal thoracic arteries and 78%, 65%, and 57% for saphenous veins. At 10 years, internal thoracic arteries were more likely than saphenous veins to be patent to left anterior descending in 99.1% of cases, to diagonals in 98.3%, to circumflex in 98.3%, to posterior descending artery in 98.5%, and to right coronary arteries in 82.5%. For right coronary arteries, saphenous vein patency was equivalent to or better than internal thoracic artery patency early after surgery. However, by 10 years, internal thoracic artery patency was better in right coronary arteries with 70% stenosis or greater. At all times after surgery and all levels of clinically important coronary stenosis, internal thoracic artery patency surpassed saphenous vein patency in grafts to the left anterior descending, diagonal, circumflex, and posterior descending arteries. CONCLUSIONS: Internal thoracic arteries demonstrate better patency than saphenous veins except when grafting moderately stenosed right coronary arteries. When bypassing right coronary arteries with less than 70% stenosis, saphenous veins may be a better choice.

Coronary Angiography↗
PubMed2025

In vitro protocol demonstrating five functional steps of trained immunity in mice: Implications on biomarker discovery and translational research.

We developed an in vitro methodology to study trained immunity using murine bone-marrow-derived macrophages stimulated with β-glucan and lipopolysaccharide (LPS). Longitudinal analysis of interleukin (IL)-6 and tumor necrosis factor (TNF) production demonstrates that trained macrophages secrete higher cytokine levels following primary stimulation with β-glucan compared to unstimulated macrophages (step 1). After a resting period, trained macrophages return to basal levels of cytokine production (step 2) but rapidly produce enhanced levels of IL-6 and TNF after secondary stimulation with LPS, compared to macrophages individually stimulated with either β-glucan (step 3) or LPS (step 4) alone. The combined cytokine production of macrophages after single stimulation with β-glucan (stimulus 1) and LPS (stimulus 2) is significantly lower than the cytokine levels produced by trained macrophages sequentially stimulated with both β-glucan and LPS (stimulus 1 + 2) (step 5). These results experimentally reproduce the distinctive functional stages that macrophages undergo during the training process.

Animals↗