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Biomedical subjects

T Mueller

Publications and source records attributed to T Mueller.

At least 55 records · Page 3Linked to original sources
PubMed1999

Rapid autologous marrow recovery and eradication of infectious mononucleosis despite severe immunosuppression following second transplantation for aplastic anemia.

A patient with aplastic anemia failed to respond to immunosuppressive therapy and first marrow transplantation (BMT). Recovery of autologous hematopoiesis was rapid following a second stem cell transplant with a non-myeloablative preparatory regimen. The autologous immune response to infectious mononucleosis (IM) 4 weeks post-transplant was normal despite recent and ongoing severe immunosuppression.

Anemia, Aplastic↗
PubMed1999

Polarity sequence, depression, and chronicity in bipolar I disorder.

Five independent studies show that polarity sequence is associated with prognosis in bipolar I disorder. Episodes in which major depression precedes mania (DMI) lead to higher morbidity than biphasic episodes which begin with mania (MDI). However, little is known about the prognostic significance of polarity sequence for long-term outcome. This study examined polarity sequence across multiple episodes among 165 bipolar I patients followed prospectively for up to 15 years as part of the NIMH Collaborative Study of Depression. Episodes beginning with major depression were significantly longer than those beginning with mania for the first three prospectively observed episodes when pooling all episode types-monophasic, biphasic, and polyphasic. Furthermore, affective polarity at onset for the first prospectively observed episode was associated with polarity at onset for the remaining three episodes. Patients whose first prospectively observed episode began with depression had higher overall morbidity during the entire follow-up period.

Adult↗
PubMed1999

SAG, a novel zinc RING finger protein that protects cells from apoptosis induced by redox agents.

SAG (sensitive to apoptosis gene) was cloned as an inducible gene by 1,10-phenanthroline (OP), a redox-sensitive compound and an apoptosis inducer. SAG encodes a novel zinc RING finger protein that consists of 113 amino acids with a calculated molecular mass of 12.6 kDa. SAG is highly conserved during evolution, with identities of 70% between human and Caenorhabditis elegans sequences and 55% between human and yeast sequences. In human tissues, SAG is ubiquitously expressed at high levels in skeletal muscles, heart, and testis. SAG is localized in both the cytoplasm and the nucleus of cells, and its gene was mapped to chromosome 3q22-24. Bacterially expressed and purified human SAG binds to zinc and copper metal ions and prevents lipid peroxidation induced by copper or a free radical generator. When overexpressed in several human cell lines, SAG protects cells from apoptosis induced by redox agents (the metal chelator OP and zinc or copper metal ions). Mechanistically, SAG appears to inhibit and/or delay metal ion-induced cytochrome c release and caspase activation. Thus, SAG is a cellular protective molecule that appears to act as an antioxidant to inhibit apoptosis induced by metal ions and reactive oxygen species.

Amino Acid Sequence↗
PubMed1998

Quinazolines: combined type 3 and 4 phosphodiesterase inhibitors.

A series of quinazolines has been prepared and evaluated for its ability to inhibit cyclic AMP phosphodiesterase type 3, type 4A, 4B and 4D. The most potent inhibitors showed IC50 values in the nanomolar range for type 3 and type 4 isoforms and bind with high affinity to the [3H]rolipram binding site. These quinazolines represent a new family of potent mixed PDE 3/4 inhibitors and are expected to have a therapeutic potential.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Growth hormone response to placebo, apomorphine and growth hormone releasing hormone in abstinent alcoholics and control subjects.

Abstinent alcoholics and control subjects were challenged with placebo (saline), growth hormone releasing hormone (GHRH) and apomorphine (APO). While both groups did not differ in their growth hormone response (HGH) to placebo and GHRH, the alcoholics revealed a significant lower HGH response to dopamine receptor stimulation with APO. These findings provide no evidence that in abstinent alcoholics HGH blunting after dopamine receptor stimulation could be related to an alteration at the pituitary level but they give neuroendocrinological support to the hypothesis of a lower dopamine receptor sensitivity in abstinent alcoholics.

Adult↗
PubMed1998

Bipolar I affective disorder: predictors of outcome after 15 years.

BACKGROUND: Robust predictors of long-term outcome in bipolar affective disorder would have substantial importance to both clinicians and researchers. Such predictors are not available, however, perhaps because of the limitations of previous efforts to find them. METHODS: In this study, 113 patients with bipolar affective disorder were followed semiannually for 5 years and annually for a subsequent 15 years. Of these, 23 (20.4%) had a poor long-term outcome indicated by the presence of mania or major depressive disorder throughout the 15th year. RESULTS: Among the baseline demographic and clinical variables tested, only active alcoholism and low levels of optimum functioning in the preceding 5 years characterized poor outcome patients. The persistence of depressive symptoms in the first 2 years of follow-up predicted depressive symptoms 15 years later but the early persistence of manic symptoms seemed to have no predictive value. A regression analysis eliminated alcoholism as an independent predictor. Thus, only poor optimal functioning in the 5 years before baseline assessment, and the persistence of depressive symptoms in the two subsequent years, were independently associated with poor, long-term prognosis. LIMITATIONS: Patients were recruited at tertiary care centers and sampling was therefore biased toward greater severity and chronicity. As is true of all naturalistic studies of course, treatment was not controlled. CONCLUSION: These findings suggest the existence of a poor outcome, depression-prone subtype of bipolar affective disorder.

Adult↗
PubMed1998

Alcoholism and drug abuse in three groups--bipolar I, unipolars and their acquaintances.

OBJECTIVE: Previous work has shown that manic-depressive illness and alcohol abuse are linked. This study further explores the relationship of alcohol and drug abuse in bipolar I patients and unipolar depressives and a comparison group obtained through the acquaintance method. METHOD: Diagnosis was accomplished according to Research Diagnostic Criteria (RDC): controls = 469; bipolars = 277; unipolar depressives = 678. Systematic data were gathered using the SADS on lifetime and current drug abuse and alcoholism. Both patients and comparison subjects were then followed prospectively for 10 years. First degree family members were interviewed using the RDC family history method. RESULTS: The group of bipolar patients and the group of unipolar patients had higher rates of drug and alcohol abuse than the comparison group when primary and secondary affective disorder patients were combined. However, primary unipolar patients did not have higher rates of alcohol or drug abuse than the comparison group. In contrast, primary bipolar patients had higher rates of alcoholism, stimulant abuse, and ever having abused a drug than the primary unipolar group and the control group. In an evaluation of the bipolar patients, drug abusers were significantly younger at intake and had a significantly younger age of onset of bipolar disorder. There was a significant increase in family history of mania or schizoaffective mania in the drug-abusing bipolar patients as compared to the non-abusing bipolar patients. LIMITATION: As in all adult samples of patients with affective illness, the chronology of alcohol and substance problems vis-à-vis the onset of illness was determined retrospectively. CONCLUSIONS: (1) Alcoholism and drug abuse are more frequent in bipolar than unipolar patients. (2) The drug abuse of bipolar patients tends toward the abuse of stimulant drugs. (3) In a bipolar patient, familial diathesis for mania is significantly associated with the abuse of alcohol and drugs. (4) More provocatively, these findings suggest the hypothesis of a common familial-genetic diathesis for a subtype of bipolar I, alcohol and stimulant abuse. CLINICAL IMPLICATIONS: The present analyses, coupled with two previous ones from the CDS, suggest that drug abuse may precipitate an earlier onset of bipolar I disorder in those who already have a familial predisposition for mania. Furthermore, in dually diagnosed patients with manic-depressive and alcohol/stimulant abuse history, mood stabilization of the bipolar disorder represents a rational approach to control concurrent alcohol and drug problems, and should be studied in systematic controlled trials.

Adult↗
PubMed1998

Interdisciplinary quality improvement from the perspective of a clinical pathway team.

Clinical pathway teams are one type of interdisciplinary team formed to improve the quality of care provided to select patient populations. As they aim to improve quality, these teams look at improving the efficiency and effectiveness of the care provided, as well as overall performance. Some clinical pathways and teams are successful, while others are not. This article describes the activities of a coronary artery bypass graft (CABG) clinical pathway team, difficulties encountered by the team, and strategies developed to overcome these difficulties.

Coronary Artery Bypass↗
PubMed1998

Lithium discontinuation and subsequent effectiveness.

OBJECTIVE: Several reports have raised concern that the discontinuation of lithium may result in treatment resistance following recurrence of affective disorder. This report explores this possibility. METHOD: The data derive from a large, naturalistic follow-up of patients with major depressive disorder or mania. Twenty-eight of the patients in the study were free of lithium and experiencing an episode of mania or schizoaffective mania diagnosed according to Research Diagnostic Criteria when they entered the study, recovered while taking lithium, later experienced a recurrence while not taking lithium, and then resumed lithium treatment. Survival analyses of time to recovery and, subsequently, time to recurrence, used continued lithium treatment as an additional censoring variable. RESULTS: Patients given lithium recovered no more quickly from their index episode than they did from their first prospectively observed episode. Moreover, lithium prophylaxis appeared no less effective after the first prospectively observed episode than after the index episode. CONCLUSIONS: These findings provide no evidence that lithium discontinuation results in treatment resistance when lithium is resumed.

Adult↗
PubMed1997

Quantitative analysis of facial motion components: anatomic and nonanatomic motion in normal persons and in patients with complete facial paralysis.

The maximal static response assay of facial motion, described in 1994, enables the simultaneous measurement of multiple facial motions by tracking the positions of specific facial points. While the maximal static response assay provides accurate measurement of facial motion, the analysis of these data lacks the simplicity of a single-number scale such as the House-Brackmann system, a subjective scale traditionally used to classify facial function. The purpose of this study was to develop a simplified numerical index capable of summarizing the data generated by the maximal static response assay in a clinically meaningful way. We also wanted to develop a method whereby only anatomic motion or nonanatomic motion in the paralyzed face could be quantitated. Anatomic motion is the motion of the specific facial points studied by the maximal static response assay that can be attributed solely to the pull of the regional facial muscles that govern the movement of those points. Nonanatomic motion is motion that is secondary to the pull of the unaffected contralateral muscles that is transmitted to the paralyzed hemiface. Thirty-four patients with complete facial paralysis were studied. The maximal static response assay was performed on all patients on presentation to the Facial Nerve Center at the University of Pittsburgh Medical Center or after development of complete facial palsy postoperatively. The data from these patients were compared with maximal static response assay data from 26 unaffected controls. The anatomic index of facial motion and the nonanatomic index of facial motion were calculated for all study participants. The anatomic index of facial motion measures anatomic facial motion, and the nonanatomic index of facial motion measures nonanatomic facial motion. To calculate the anatomic index of facial motion, the vector magnitudes of the supraorbital, infraorbital, and modiolar motions during brow lift, eye closure, and smile are summed. The anatomic index of facial motion represents a ratio of this sum on the affected side to the corresponding sum on the unaffected side using only anatomic motions. The nonanatomic index of facial motion is a similar ratio using nonanatomic motion only (i.e., motions in directions that cannot be produced by the ipsilateral muscles). The anatomic index of facial motion represents a single number that can be used to assess facial motion. The value of the anatomic index of facial motion for patients with complete facial paralysis is 0.07 +/- 0.08. The anatomic index of facial motion for normal individuals is 1.05 +/- 0.13 (p < 0.0001, Mann-Whitney rank-sum test). The nonanatomic index of facial motion in normal individuals is 0.05 +/- 0.08; in patients with complete facial paralysis, it is 0.34 +/- 0.32 (p < 0.0001, Mann-Whitney rank-sum test). During recovery from complete facial paralysis, the anatomic index of facial motion and the nonanatomic index of facial motion each revert steadily toward normal values. The anatomic index of facial motion and the nonanatomic index of facial motion are single numbers based on the maximal static response assay, which quantitatively describes anatomic motion and nonanatomic motion in patients with complete facial paralysis. Although patients with complete facial paralysis have motion on the paralyzed hemiface, the motion is primarily nonanatomic. Both indices can be used to track recovery from complete facial paralysis.

Adolescent↗
PubMed1995

The likelihood of recurrence in bipolar affective disorder: the importance of episode recency.

These analyses used a high-intensity follow-up of of patients with bipolar affective disorder to describe the immediate and long-term risks for recurrence and the importance of sustained recovery to those risks. At the baseline evaluation, all patients were in episodes of Research Diagnostic Criteria major depressive disorder, mania or schizoaffective disorder (excluding the mainly schizophrenic subtype); those who were depressed at intake had a history of mania or schizoaffective mania. Raters re-evaluated these patients at 6-month intervals for 5 years and annually for the remainder of a 10-year follow-up. The following report describes relapse risks for the 186 patients observed to recover from their index episodes. Survival analyses quantified the likelihood of relapse over time, beginning after symptom-free periods of 4 months and 1, 2 and 3 years. Further survival analyses used treatment status as a censoring variable to estimate the eventual likelihood of recurrence among those who reported sustained compliance with lithium prophylaxis; the prophylaxis group remained under observation until they relapsed, were lost to follow-up or ceased taking lithium. Progressively longer symptom-free periods were clearly associated with lower relapse risks over the subsequent 4 years. Thereafter, however, this effect dissipitated. 7 years after recovery, the cumulative likelihood of recurrence was four in five for all bipolar patients and two in three for those whose index episode had been followed by at least 3 years without symptoms. Even with sustained lithium prophylaxis, the likelihood of at least one recurrence exceeded 70% within 5 years of recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Alcoholism in manic-depressive (bipolar) illness: familial illness, course of illness, and the primary-secondary distinction.

OBJECTIVE: This 5-year follow-up study was designed to explore the factors that might lead to alcoholism in patients with bipolar disorder. METHOD: The authors studied patients with bipolar illness (70 with alcoholism and 161 without), their relatives, and a comparison group composed of relatives' acquaintances. All were evaluated with versions of the Schedule for Affective Disorders and Schizophrenia, and diagnoses were made according to the Research Diagnostic Criteria. Thirty of the bipolar alcoholic patients whose affective disorder was primary were also compared with 34 whose alcoholism was primary. RESULTS: Alcoholism was more frequent in the bipolar patients than in the comparison subjects. There no significant differences between the alcoholic and nonalcoholic bipolar patients in family history of alcoholism or affective disorders, suggesting that bipolar illness with alcoholism is not explicable by a family history of alcoholism and that the alcoholism seen in bipolar illness is dissimilar to alcoholism as a primary disorder. Alcoholism associated with bipolar illness was more likely to remit than primary alcoholism. There was no significant difference in family history between the patients with primary alcoholism and those with primary bipolar disorder. The patients with primary alcoholism had significantly fewer episodes of affective disorder during followup, suggesting that their type of bipolar illness was less severe and may have needed the added insult of alcoholism to make it manifest. CONCLUSIONS: The study supports the idea that not all alcoholism is primary with a corresponding familial diathesis. Rather, alcoholism associated with bipolar disorder is often a secondary complication.

Adult↗
PubMed1995

Characteristics and significance of untreated major depressive disorder.

OBJECTIVE: This study sought to describe the characteristics and consequences of untreated major depressive disorder. METHOD: As part of a family study of probands with major affective disorders, raters assessed 3,119 first-degree relatives, spouses, and comparison subjects. When 2,237 (71.7%) of these individuals were reassessed 6 years later, 547 had experienced episodes of major depressive disorder in the interval. Those who had sought any form of treatment for any episode of major depressive disorder in the interval were compared, by baseline demographic characteristics and clinical features of their worst episodes of major depressive disorder, to those who had not. Individuals who had had untreated major depressive disorder were then compared, by changes in socioeconomic status and by levels of psychosocial impairment at follow-up, to a matched group with no major depressive disorder in the interval. RESULTS: The worst episodes of 313 treated individuals, compared to those of 234 untreated individuals, were characterized by older age, symptoms of the endogenous subtype, longer durations, and the presence of disruption in role function. Each of these factors contributed independently to the distinction between treated and untreated episodes. Untreated individuals experienced significant psychosocial impairment on follow-up but did not show the economic disadvantages shown elsewhere for probands who began follow-up as they sought treatment at tertiary medical centers. CONCLUSIONS: These data suggest that illness characteristics and age determine the decision to seek treatment for major depressive disorder. Untreated depression is apparently associated with long-standing psychosocial difficulties but not with serious economic consequences.

Adolescent↗
PubMed1994

Receptor binding properties of four-helix-bundle growth factors deduced from electrostatic analysis.

Hormones of the hematopoietin class mediate signal transduction by binding to specific transmembrane receptors. Structural data show that the human growth hormone (hGH) forms a complex with a homodimeric receptor and that hGH is a member of a class of hematopoietins possessing an antiparallel 4-alpha-helix bundle fold. Mutagenesis experiments suggest that electrostatic interactions may have an important influence on hormone-receptor recognition. In order to examine the specificity of hormone-receptor complexation, an analysis was made of the electrostatic potentials of hGH, interleukin-2 (IL-2), interleukin-4 (IL-4), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and the hGH and IL-4 receptors. The binding surfaces of hGH and its receptor, and of IL-4 and its receptor, show complementary electrostatic potentials. The potentials of the hGH and its receptor display approximately 2-fold rotational symmetry because the receptor subunits are identical. In contrast, the potentials of GM-CSF and IL-2 lack such symmetry, consistent with their known high affinity for hetero-oligomeric receptors. Analysis of the electrostatic potentials supports a recently proposed hetero-oligomeric model for a high-affinity IL-4 receptor and suggests a possible new receptor binding mode for G-CSF; it also provides valuable information for guiding structural and mutagenesis studies of signal-transducing proteins and their receptors.

Electrochemistry↗
PubMed1994

Manic-depressive (bipolar) disorder: the course in light of a prospective ten-year follow-up of 131 patients.

For a five-year period, 131 bipolar patients were followed every 6 months; for the next 5 years, they were followed yearly. Each patient was interviewed in a systematic way that gave information about episodes, hospitalizations, cycle lengths and the presence of alcoholism. Women and men were not significantly different in the number of follow-up manic or depressive episodes or hospitalizations. Chronicity from index episode to the end of the 10-year follow-up was uncommon (4%). Alcoholism, which was common in these patients, showed a great diminution at the end of 10 years. Contrary to expectation, cycle lengths showed no systematic decrease in length over the follow-up. In this naturalistic study, treatment intensity was not related to decreasing episodes or to changes in cycle length. The number of episodes in the first 5 years of follow-up was not correlated with the number of episodes in the last 5 years. Cycle lengths in the first 5 years of follow-up were similar in length to the last 5 years of follow-up. A family history of mania in these bipolar patients was associated with more episodes in follow-up than if such a family history were absent. The patients whose alcoholism predated the onset of their affective illness were less likely to have episodes in the follow-up than the patients in whom affective illness predated the onset of the alcoholism.

Adult↗
PubMed1992

Effect of daytime on resting energy expenditure and thermic effect of food in obese adolescents.

The aim of this study was to investigate the effect of daytime on resting energy expenditure (REE) and thermic effect of food (TEF), REE and TEF were measured in 11 obese boys (mean age +/- SD 11.9 +/- 1.6 years; body mass index 30.1 +/- 4.0 kg/m2) by indirect calorimetry (SensorMedics 2900) on two consecutive days: early in the morning (7:30 a.m.) on one day and at 12 noon on the other day or vice versa. REE was measured for 30 minutes and TEF for 180 minutes after a 600 kcal liquid meal containing 13% protein, 39% fat and 48% carbohydrates. REE measured in the morning was not statistically different from that measured at noon (2191 +/- 358 vs 2223 +/- 319 kcal/24 hours) and morning values were highly correlated with afternoon values (r2 = 0.805). Therefore we conclude that the effect of daytime is negligible for measurements of REE if the patients are in a postabsorptive state and avoid physical activity and stress 10-12 hours prior to measurements. The thermic effect of food calculated in the morning also was not statistically significantly from values found in the afternoon (8.2 +/- 8.8% in the morning and 6.6 +/- 7.5% in the afternoon). However, because of very high within-patient variability the correlation between morning and afternoon values was weaker than for REE (r2 = 0.289).

Adolescent↗
PubMed1992

Cardiovascular risk factors in obese children in relation to weight and body fat distribution.

To assess the relationship between obesity and body fat distribution with cardiovascular risk factors in children, various measures of obesity and waist-to-hip circumference ratio (WHR) were related to serum lipids, lipoproteins, apolipoproteins, glucose, insulin, uric acid, systolic (SBP) and diastolic blood pressure (DBP). In boys univariate analysis revealed an association of triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), the ratio ApoAI/ApoB, cholesterol/HDL-C, glucose and insulin to WHR. SBP and DBP and serum uric acid correlated with all measures of obesity [body mass index (BMI), percent overweight, percent body fat, skinfolds], but not with WHR. In girls lipid parameters (triglycerides, LDL-C, HDL-C, HDL2, ApoAI, ApoB) and atherogenic ratios correlated with measures of obesity and WHR. Glucose, insulin, SBP and DBP showed the highest correlation with WHR (r = 0.598, p less than 0.001 and r = 0.713, p less than 0.001). Multivariate analysis in girls revealed a first step dependency of ApoAI, the ratio cholesterol/ApoAI, insulin, SBP and DBP on WHR, triglycerides, HDL-C, LDL-C and the ratio ApoAI/ApoB, a first step dependency on percent body fat mass. In boys triglycerides, ApoB and the ratio ApoAI/ApoB were related to WHR for insulin, SBP and DBP, but a positive association with the WHR was found, explaining 33, 21.8, and 22.6% of the variance. This study demonstrates that cardiovascular risk factors in obese children are related to obesity and body fat distribution. Obese children with predominantly abdominal fat mass show a risk profile that is less favorable than gluteal-femoral fat distribution. Evaluation of body fat distribution in obese children, therefore, may help to identify persons most susceptible to cardiovascular risk in adulthood.

Adipose Tissue↗