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Biomedical subjects

T Mueller

Publications and source records attributed to T Mueller.

At least 37 records · Page 2Linked to original sources

Relation between homocysteine and non-fatal stroke in peripheral arterial disease.

There are currently no data on whether high total serum homocysteine (tHcy) is predictive for cerebrovascular events in patients with symptomatic peripheral arterial disease (PAD). Therefore, the purpose of this study was to determine whether high tHcy levels were related to the evidence of non-fatal stroke in PAD. Evidence of non-fatal atherothrombotic stroke events was verified in 450 consecutive male patients, admitted for inpatient treatment of symptomatic PAD. The extent of carotid stenosis was evaluated by colour duplex Doppler measurement and fasting tHcy was determined by high-performance liquid chromatography. Within the population of 450 PAD patients a documented history of ischaemic stroke was evident in 50 subjects. The median tHcy values were significantly higher in PAD patients with stroke (18.6 micromol/l) than in PAD patients without stroke (15.1 micromol/l, P < 0.001). Logistic regression analysis revealed that tHcy was an independent and significant predictor (P=0.001) with an odds ratio (OR) of 1.37 for an increment of 5 micromol/l. In this multivariate model, diabetes mellitus (OR=2.34, P=0.011) and carotid stenosis > or =50% (OR=2.59, P=0.005) were also independently related to clinical cerebrovascular disease in PAD. In conclusion, the present study demonstrates an association of tHcy and evidence of non-fatal atherothrombotic stroke in patients with symptomatic PAD. This could be important, as a reduction of elevated tHcy concentrations by vitamin supplement might decrease the high frequency of cerebrovascular complications in PAD patients.

Aged↗

Erythrocyte mean cellular volume and its relation to serum homocysteine, vitamin B12 and folate.

Cobalamin (B12) and folate deficiency is related to both increased erythrocyte mean cellular volume (MCV) and raised serum total homocysteine (tHcy) values. Furthermore, there are indications that B12 and folate serum values do not represent the tissue status of the two vitamins exactly. Therefore, a direct relationship between MCV and tHcy, if demonstrated, could support the hypothesis that tHcy is a better indicator for the cited vitamin status than the serum levels of B12 and folate. We studied MCV, gamma glutamyl transferase (GGT), serum B12, folate and tHcy values in 200 hospitalized patients. There was a significant correlation of MCV with GGT (r = 0.266, P < 0.001) and with tHcy (r = 0.248, P < 0.001), but not with serum B12 and folate. Stepwise multiple linear regression with MCV as dependent and GGT, B12, folate and tHcy as independent variables, respectively, revealed significant associations of MCV with GGT (B = 2.18, 95% CI 0.95-3.42, P = 0.001) and tHcy (B = 3.33, 95% CI 1.26-5.39, P = 0.002). By removing tHcy from this model, serum B12 became a significant predictor of MCV (B = -1.70, 95% CI -3.25 to -0.15, P = 0.032). Serum folate was not significantly associated with MCV in multivariate analysis. In conclusion, the present study confirms indications that serum B12 and folate values lack clinical sensitivity and specificity in diagnosing vitamin deficiency states by showing MCV was better associated to tHcy, than to B12 or folate serum levels. This observation demonstrates that tHcy may be useful in diagnosing patients with B12 and/or folate deficiency.

Cerebrovascular Disorders↗

Field trial with oral vaccination of dogs against rabies in the Philippines.

BACKGROUND: The potential role of oral vaccination of dogs against rabies in the Philippines was investigated in terms of safety and efficacy. METHODS: Prior to the vaccination campaign, a house-to-house survey was carried out to collect data on the dog population in the study area, the coastal village of Mindoro. During the vaccination campaign all households were visited again, and all dogs encountered (>2 months old) were, if possible, vaccinated. Furthermore, 14 dogs vaccinated were bled on different occasions. RESULTS: During the survey, a total of 216 dogs were counted, and none of these animals had previously been vaccinated against rabies. Only 17 dogs could be restrained and subsequently vaccinated directly by the vaccinators. Another 126 dogs were offered a local-made boiled intestine bait, containing a capsule filled with 3.0 ml SAD B19 (107.9 FFU/ml). The bait acceptance rate of dogs offered a bait was 96.1%. The vaccination coverage of the dog population (> 2 months old) estimated by the number of animals vaccinated directly and the number of dogs that accepted a bait and subsequently punctured the vaccine container was 76%. Fifteen and 29 days after the vaccination campaign 6 and 10 dogs (n = 14) had rabies virus neutralizing antibody titres of >/= 0.5 IU/ml, respectively. No unintentional contacts of nontarget species, including humans, with the vaccine virus were reported. CONCLUSIONS: The results of the campaign show that oral vaccination of dogs against rabies is a promising supplementary method in dog rabies control in the Philippines.

Administration, Oral↗

White matter disease in children treated for malignant brain tumors.

OBJECTS: The objects of the study reported were to recognize different patterns of white matter disease (WMD) in the follow-up of children after surgery, radiation and/or chemotherapy for malignant primary brain tumors and to evaluate statistical data on the incidence of WMD and various risk factors. METHODS: Magnetic resonance imaging (MRI) records were evaluated retrospectively in the routine follow-up (range 6 months to 15 years after surgery) of 44 children with malignant primary brain tumors treated with surgery and radiotherapy and/or chemotherapy. RESULTS: WMD was diagnosed in 28 children and subclassified into circumscribed white matter lesions (WML) and diffuse atrophy. WML were the most common finding ( n=13), followed by atrophy ( n=7) and the combination of both ( n=8). Statistical analysis revealed slightly more frequent atrophy in children younger than 5 years. WML could be linked with supratentorial location of the tumor, follow-up longer than 5 years, and the presence of a ventricular shunt. Intrathecal chemotherapy was also a factor, but because of the small sample size of the group this might not be valid. None of the children had neurological deficits attributed to these findings, but the impact on neuropsychological development was not determined.

Adolescent↗

Developing a vasopressor combination in a pig model of adult asphyxial cardiac arrest.

BACKGROUND: The purpose of this study was to investigate the effects of vasopressin versus epinephrine, and both drugs combined, in a porcine model of simulated adult asphyxial cardiac arrest. METHODS AND RESULTS: At approximately 7 minutes after the endotracheal tube had been clamped, cardiac arrest was present in 24 pigs and remained untreated for another 8 minutes. After 4 minutes of basic life support cardiopulmonary resuscitation, pigs were randomly assigned to receive, every 5 minutes, either epinephrine (45, 200, or 200 microgram/kg; n=6); vasopressin (0.4, 0.8, or 0.8 U/kg; n=6); or epinephrine combined with vasopressin (high-dose epinephrine/vasopressin combination, microgram/kg and U/kg: 45/0.4, 200/0.8, or 200/0.8; n=6; optimal-dose epinephrine/vasopressin combination, 45/0.4, 45/0.8, or 45/0.8; n=6). Mean+/-SEM coronary perfusion pressure was significantly (P<0.05) higher 90 seconds after high- or optimal-dose epinephrine/vasopressin combinations versus vasopressin alone and versus epinephrine alone (37+/-10 versus 25+/-7 versus 19+/-8 versus 6+/-3 mm Hg; 42+/-6 versus 40+/-5 versus 21+/-5 versus 14+/-6 mm Hg; and 39+/-6 versus 37+/-4 versus 9+/-3 versus 12+/-4 mm Hg, respectively). Six of 6 high-dose, 6 of 6 optimal-dose vasopressin/epinephrine combination, 0 of 6 vasopressin, and 1 of 6 epinephrine pigs had return of spontaneous circulation (P<0.05). CONCLUSIONS: Epinephrine combined with vasopressin, but not epinephrine or vasopressin alone, maintained elevated coronary perfusion pressure during cardiopulmonary resuscitation and resulted in significantly higher survival rates in this adult porcine asphyxial model.

Animals↗

Non-linear changes of electrocortical activity after antenatal betamethasone treatment in fetal sheep.

We determined the effects of betamethasone on the fetal sheep electrocorticogram (ECoG) using linear (power spectral) and non-linear analysis. For non-linear analysis we used an algorithm based on the Wolf algorithm for the estimation of the leading Lyapunov exponent which calculates a prediction error based on the course of the time series in the phase space. A high prediction error stands for low predictibility or low regularity and vice versa. After 48 h of baseline recordings, vehicle (n = 6) or betamethasone (n = 7) at 10 microg h(-1) was infused over 48 h to the sheep fetus at 128 days gestational age (0.87 of gestation). ECoG spectral analysis revealed no difference in power spectrum between vehicle- and betamethasone-treated fetuses. The prediction error of the ECoG during REM sleep was higher than during non-REM or quiet sleep in both groups (P < 0.0001) revealing lower causality of brain activity during REM sleep. During REM sleep, prediction error significantly decreased 18-24 h after onset of betamethasone treatment (P < 0.05) and returned to baseline values within the following 24 h of continued betamethasone treatment. No ECoG changes were found during quiet sleep. Non-linear ECoG changes during metabolically active REM sleep accompanied the previously described decrease in cerebral blood flow. These results suggest that betamethasone in doses used in perinatal medicine acutely alters complex neuronal activity.

Algorithms↗

MRI in the diagnosis of a peritoneal leak in continuous ambulatory peritoneal dialysis.

Mechanical problems in continuous ambulatory peritoneal dialysis (CAPD) can result in ultrafiltration failure and disruption of CAPD therapy. The recently described tool of CT peritoneography with water-soluble contrast medium has the disadvantage of radiation and instillation of nephrotoxic substances. We report a child with a peritoneal leak diagnosed by MRI after instillation of a gadodiamide-dialysate mixture. This method provided good anatomical detail without radiation or nephrotoxic agents.

Child↗

The significance of psychotic features in manic episodes: a report from the NIMH collaborative study.

BACKGROUND: Psychotic features in the context of major depressive syndromes have correlates in symptom severity, acute treatment response and long-term prognosis. Little is known as to whether psychotic features have similar importance when they occur within manic syndromes. METHODS: These data derive from a multi-center, long-term follow-up of patients with major affective disorder. Raters conducted follow-up interviews at 6-month intervals for the first 5 years and annually thereafter. A sub-set of probands participated in a family study in which all available, adult, first-degree relatives were interviewed as well. RESULTS: Of 139 who entered the study in an episode of mania, 90 patients had psychotic features. Symptom severity ratings at intake were more severe for this group. Though time to first recovery and time to first relapse did not distinguish the groups, psychotic features were associated with a greater number of weeks ill during follow-up and the strength of this association was similar to that seen for psychotic features within depressed patients described in an earlier publication. Patients with psychotic mania at intake did not differ significantly from those with nonpsychotic mania by response to acute lithium treatment, suicidal behavior during follow-up, or risks for affective disorder among first-degree relatives. Psychotic features within manic syndromes were not associated with high psychosis ratings during follow-up. In contrast, when psychotic features accompanied depressive syndromes, they strongly predicted the number of weeks with psychosis during follow-up, particularly among individuals whose episodes at intake were less acute. CONCLUSIONS: As with major depressive syndromes, psychotic features in mania are associated with greater symptom severity and higher morbidity in the long-term. Psychotic features are much less predictive of future psychosis when they occur within a manic syndrome than when they occur within a depressive syndrome.

Activities of Daily Living↗

Disease activated drugs: a new concept for the treatment of asthma.

Disease activated drugs (DAD) are pro-drugs of one active principle or combinations of two drugs, which have a proven efficacy for the treatment of the target disease. In opposition to pro-drugs, DAD are activated in inflamed but not normal tissues. Due to the disease specific activation, the amount of locally released drug(s) should be related directly to the severity of the inflammation. To test this concept in asthma a PDE4 inhibitor, an isoquinoline derivative, was chemically derivatized into pro-drugs or combined with corticosteroids. These new compounds were more readily cleaved into active PDE4 inhibitor, in bronchoalveolar lavage fluid (BALF) from Brown-Norway rats with lung inflammation than in BALF from rats without airway inflammation. The DAD concept (local selective release and improved therapeutic window) was validated in vivo using the inhibition of methacholine induced bronchoconstriction in guinea pigs with or without ozone induced lung inflammation. An example of DAD hydrolysis (isoquinoline-dexamethasone) was also examined in BALF from asthmatics and healthy volunteers.

Animals↗

R-Mix cells are faster, at least as sensitive and marginally more costly than conventional cell lines for the detection of respiratory viruses.

OBJECTIVE: To evaluate shell vials of R-Mix, a combination of mink lung cells and human adenocarcinoma cells (strains Mv1Lu and A549, respectively, Diagnostic Hybrids, Athens, OH) to detect respiratory viruses from prospective clinical respiratory specimens and frozen stocks. STUDY DESIGN: We compared the performance of R-Mix to conventional culture (CC) using tubes of PMK, Hep-2, and MRC5 to detect respiratory viruses from fresh clinical specimens. For each respiratory specimen submitted to virology, two shell vials of R-Mix were inoculated and examined twice (generally after 24 and 48 h) by an indirect test with a pool of immunofluorescent antisera to influenza A and B, adenovirus, parainfluenza 1-3 and RSV (DAKO, Carpinteria, CA). If positive, testing with monoclonal antisera was done. CCs were incubated for 10 days, examined daily for cytopathological effect, hemadsorbed twice and stained if positive. Cost comparison was done. Lastly, respiratory viruses frozen from previous years were inoculated onto R-Mix. RESULTS: R-Mix was positive for all 29 frozen virus stocks. In the clinical trial, 396 prospective specimens were inoculated into R-Mix and CC. R-Mix identified 21 specimens as respiratory virus positive; CC identified 19. Turn-around time of R-Mix for positive specimens was 1.4 days; for CC it was 5.2 days. Turn-around time of R-Mix for all specimens (positive and negative) was 2.0 days; for CC it was 9.8 days. The overall cost of R-Mix was approximately 11% more than that of CC. CONCLUSION: R-Mix enabled rapid identification of all the frozen virus stocks representing the seven major respiratory viral groups. When compared to CC, R-Mix was slightly more sensitive than three cell lines (four tubes) used in CC but it was several days faster.

Adenovirus Infections, Human↗

Lithium and suicidal behavior in major affective disorder: a case-control study.

OBJECTIVE: A number of studies have suggested that lithium may be particularly effective in reducing suicide risks among patients with major affective disorders. The design of many of these studies left them open to biases associated with treatment compliance, however. METHOD: Subjects were drawn from a naturalistic, long-term follow-up of patients with major affective disorders. Fifteen who committed suicide while receiving somatotherapy where matched to non-suicidal patients who were similarly receiving somatotherapy at the same point in follow-up. The same procedure was followed for 41 patients who made a serious suicide attempt during follow-up. RESULTS: Six (40.0%) of the patients who committed suicide, and eight (53.3%) of their controls, were thought to have been taking lithium in the preceding week. Among attempters and their controls, nine (22.0%) and eight (19.5%), respectively, were taking lithium. CONCLUSION: These results do not support previous suggestions that lithium has uniquely antisuicidal properties. Other existing datasets should be explored with this design to establish whether lithium does, or does not, offer special protection against suicide.

Adult↗

Peritoneal dialysate fluid composition determines heat shock protein expression patterns in human mesothelial cells.

BACKGROUND: Low biocompatibility of peritoneal dialysis fluids (PDF) contributes to mesothelial injury. We investigated whether the heat shock proteins (HSP)-27, HSP-72, and HSP-90 are differentially induced upon exposure of mesothelial cells to PDF and whether this was affected by selective modulation of the physicochemical properties of PDF. METHODS: Human mesothelial cells (Met5A and primary human mesothelial cells) were exposed to acidic lactate and glucose-monomer based PDF (CAPD2 and CAPD3), to control culture media, or to a neutral lactate and glucose-monomer-based PDF with reduced levels of glucose degradation products (BALANCE). Expression of HSP-27, HSP-72, and HSP-90 and cellular distribution of HSP-72 were assessed by Western blotting and immunocytochemistry. RESULTS: Mesothelial cells exhibited strong constitutive expression of HSP-27 and to a lesser extent HSP-72 and HSP-90. Exposure of the cells to CAPD2 and CAPD3 resulted in strong up-regulation of HSP-72. HSP-27 levels were slightly increased, but HSP-90 levels were unchanged upon exposure to CAPD2 or CAPD3. In contrast, exposure of the cells to BALANCE did not affect HSP-27 or HSP-72 expression. The acidic pH and glucose degradation products were found to be principal in mediating increased HSP-72 expression upon exposure to PDF. CONCLUSIONS: Analysis of HSP expression represents a novel tool to assess biocompatibility of PDF. Among the HSP investigated, HSP-72 is the most predictive and accurate parameter to assess mesothelial cell injury in the early phase of exposure to PDF.

Cells, Cultured↗

Association between erythrocyte mean corpuscular volume and peripheral arterial disease in male subjects: a case control study.

Elevated serum total homocysteine, an established risk factor for peripheral arterial disease, is influenced by the vitamin B12 and folate status. Since these vitamins are inversely correlated with erythrocyte mean corpuscular volume, an investigation of whether mean corpuscular volume is higher in patients with symptomatic peripheral arterial disease than in healthy subjects was performed. Furthermore, a determination of predictors of increased mean corpuscular volume levels in this population free of symptomatic coronary artery disease, cerebrovascular disease, and diabetes mellitus was carried out. From 469 consecutive patients with symptomatic peripheral arterial disease, 100 fulfilled study inclusion criteria. Peripheral arterial disease was confirmed by angiography. One hundred age-matched subjects without peripheral arterial disease as verified by ankle-brachial index measurements >0.9 served as control subjects. Patients with PAD displayed a significantly higher mean corpuscular volume level (94.5 fl) than control subjects (90.9 fl, p<0.001). Logistic regression analysis showed that current smoking status (p<0.001) and mean corpuscular volume (p=0.009), but not total homocysteine or lipid parameters discriminated case control status. In addition, logistic regression analysis revealed a relationship of mean corpuscular volume with smoking (p=0.001), gamma-glutamyltransferase (p<0.001), and total homocysteine (p=0.012). This model predicted mean corpuscular volume values with an accuracy of 83%. Elevated mean corpuscular volume is a predictor of symptomatic peripheral arterial disease in the sample studied. A deficiency of folate and/or vitamin B12 may be responsible for this observation, as indicated by the correlation of mean corpuscular volume with total homocysteine. Due to the additional association of mean corpuscular volume with smoking and gamma-glutamyltransferase, an unhealthy lifestyle with low vitamin intake may cause elevated mean corpuscular volume values in patients with PAD.

Adult↗

Total serum homocysteine--a predictor of extracranial carotid artery stenosis in male patients with symptomatic peripheral arterial disease.

High total serum homocysteine (tHcy) concentrations are associated with an increased risk of carotid artery disease in the general population. Since patients with peripheral arterial disease (PAD) have a threefold risk of cerebrovascular morbidity compared to individuals free of PAD, and since the total neurological event rate is associated with a > or = 50% lumen reduction in extracranial carotid arteries, it was tested whether tHcy is a predictor of internal carotid artery stenosis in patients with symptomatic PAD. A total of 443 consecutive male PAD patients without previous carotid surgery/stenting were studied. In all, 100 patients with PAD had an internal carotid artery stenosis > or = 50%. Of the remaining 343 patients, 100 individuals matched for age (+/- 2 years) and diabetes served as controls. The extent of carotid stenosis was evaluated with color duplex measurement; tHcy was determined by high-performance liquid chromatography. Cases displayed a significantly higher median fasting tHcy level (17.0 micromol/l) than controls (13.7 micromol/l, p=0.001). Multivariate analysis showed that tHcy (p=0.036) was an independent predictor of internal carotid artery stenosis > or = 50% in PAD patients, representing an odds ratio of 1.32 (95% CI, 1.02-1.72) for an increment of 5 micromol/l. In the present study, high tHcy was an independent risk factor for an internal carotid artery stenosis > or = 50% in patients with PAD. Since PAD patients suffer a threefold risk of stroke compared to healthy individuals, a simple vitamin substitution in PAD patients may reduce the occurrence of internal carotid artery stenosis and therefore diminish the relatively high rate of cerebrovascular events in this population.

Aged↗

Impact of atherosclerotic risk factors on the anatomical distribution of peripheral arterial disease.

BACKGROUND: The aim of the study was to determine predictors of hemodynamically relevant atherosclerosis (HRA) in different segments of lower limb arteries in patients with peripheral arterial disease (PAD). METHODS: In a retrospective case-control study 106 hospitalized consecutive patients with symptomatic PAD and 52 asymptomatic control subjects were studied. All patients underwent distal aortofemoral angiography. The arteries of the lower limbs were divided into three sections: in the aorto-iliac and femoro-popliteal segments HRA was defined as one or more stenosis of over 50%. In the crural segment it was considered if at least two arteries of one lower leg had occlusions/stenoses of over 50%. RESULTS: In 106 patients, there were 132 cases of hemodynamically relevant lesions, and in 26 patients in two segments. We separately compared 23 cases with aorto-iliac, 82 with femoro-popliteal and 27 with crural manifestation to the 52 control subjects. Calculating age- and sex-adjusted odds ratios, we found that current smoking status and plasminogen levels were significantly associated with HRA in the aorto-iliac and femoro-popliteal segments, whereas in diabetes mellitus the association was found to be in the crural and femoro-popliteal segments. However, there was no such association for lipid profiles and fibrinogen. CONCLUSIONS: We conclude that the anatomic distribution of HRA in patients with PAD is different according to the risk factor profile. The aorto-iliac and crural segments show specific risk profiles while the femoro-popliteal segment seems to be a transition zone. Smoking and high plasminogen levels may be related to atherosclerosis of proximal segments, diabetes to that of the distal segments.

Aged↗

Clinical and financial benefits of rapid detection of respiratory viruses: an outcomes study.

To assess the expected benefits of rapid reporting of respiratory viruses, we compared patients whose samples were processed using standard techniques such as enzyme immunoassays, shell vial assays, and culture tube assays (year 1) to patients whose samples were processed with the same standard techniques in addition to immunofluorescent testing (FA) directly on cytocentrifuged samples (year 2). The cytospin FA screened for influenza A and B viruses, respiratory syncytial virus (RSV), parainfluenza viruses 1 to 3, and adenovirus (DAKO Diagnostics Ltd.). The specificity of the cytospin FA for all viruses was 100%. The sensitivities for influenza A virus and RSV were 90 and 98%, respectively, but the sensitivities for influenza B virus and adenovirus were unacceptable (14.3 and 0%, respectively). However, since the former viruses account for >85% of our isolates from clinical specimens, the cytospin FA is an excellent screening test since the positive result was available within hours. The mean turnaround time for all positive viruses was 4.5 days in year 1 and 0.9 day in year 2 (P = 0.001). This rapid reporting resulted in physicians having access to information sooner, enabling more appropriate treatment. The mean length of stay in the hospital for inpatients with respiratory viral isolates was 10.6 days for year 1 versus 5.3 days for year 2. Mean variable costs for these patients was $7,893 in year 1 and $2,177 in year 2. After subtracting reagent costs and technological time, the savings in variable costs was $144,332/year. Summarizing, the cytospin FA markedly decreased turnaround time and was associated with decreased mortality, length of stay, and costs and with better antibiotic stewardship.

Centrifugation↗

Does incomplete recovery from first lifetime major depressive episode herald a chronic course of illness?

OBJECTIVE: This study investigated the influence of incomplete recovery from first lifetime major depressive episodes on long-term outcome. METHOD: After their first lifetime major depressive episode, patients were divided into asymptomatic (N=70) and residual subthreshold depressive symptom (N=26) recovery groups and compared on longitudinal course during up to 12 years of prospective naturalistic follow-up. RESULTS: Patients with residual subthreshold depressive symptoms during recovery had significantly more severe and chronic future courses. Those with residual symptoms relapsed to major and minor depressive episodes faster and had more recurrences, shorter well intervals, and fewer symptom-free weeks during follow-up than asymptomatic patients. CONCLUSIONS: Resolution of major depressive episodes with residual subthreshold depressive symptoms, even the first lifetime episode, appears to be the first step of a more severe, relapsing, and chronic future course. When ongoing subthreshold symptoms continue after major depressive episodes, the illness is still active, and continued treatment is strongly recommended.

Antidepressive Agents↗