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Biomedical subjects

M M Weber

Publications and source records attributed to M M Weber.

At least 37 records · Page 2Linked to original sources
PubMed2000

Surgical management of unstable angina and symptomatic coronary artery disease.

The treatment of coronary artery disease and, in particular, acute coronary syndromes has evolved from watchful waiting to an early aggressive intervention strategy. Patients are currently receiving either percutaneous or surgical revascularization. Several major clinical trials have identified those patients mostly likely to benefit from surgical intervention. These patients typically include those with left-main coronary artery disease, triple vessel disease with decreased left ventricular function, and other clinical risk factors. As a result of these studies, unique needs and outcomes of special populations have been identified. This article will present an overview of surgical treatment of coronary artery disease with emphasis on patient selection with particular attention to women, older persons, diabetic patients, and innovations in surgical techniques that may improve patient outcomes.

Aged↗
PubMed2000

Psychiatric research and science policy in Germany: the history of the Deutsche Forschungsanstalt fur Psychiatrie (German Institute for Psychiatric Research) in Munich from 1917 to 1945).

The Deutsche Forschungsanstalt fur Psychiatrie (DFA) in Munich, one of the most important research institutes in the field of theoretical and clinical psychiatry, was founded in 1917 by Emil Kraepelin. Its financial existence between the world wars was assured by generous donations from the Jewish American scholar and philanthropist James Loeb. The scientific work done by Walther Spielmeyer (neuropathology), Felix Plaut (serology), Kurt Schneider (clinical psychiatry) and Ernst Rudin (psychiatric genetics) earned the DFA a reputation as an international center for psychiatry and neurology. During the 'Third Reich' Ernst Rudin cooperated with the National Socialist health system. His genetic concepts provided support for eugenic programmes such as forced sterilization of individuals with psychoses. These complex interactions underscore the importance of the DFA in understanding the recent history of medicine in Germany.

Academies and Institutes↗
PubMed2000

[The development of modern psychopharmacology. Historical aspects of therapeutic claims and capabilities].

Even though psychopharmacology is an integral part of modern psychiatric treatment, it remains a controversial topic in public discourse. Historical analysis is an important tool, which gives us a more realistic view of the theoretical underpinnings and therapeutic potential of psychopharmacological treatments. Not surprisingly, a historical survey of claims and treatments shows that psychopharmacological developments are closely connected to the intellectual framework of the period. While drugs have been used to treat psychopathological disorders since ancient times, post-19th century modern psychopharmacology has been characterized by its reliance on science. This study examines this reliance on scientific disciplines, such as chemistry and anesthesiology, by examining case studies such as the introduction of new psychopharmacological techniques. For instance, the introduction in 1869 of the first synthetic sedative, chloral hydrate, clearly illustrates several trends in modern psychopharmacology. The successful introductions of antipsychotic and antidepressant drugs in the late 1950s have also been important milestones, which were instrumental in breaking down the skepticism of clinical psychiatrists.

History, 19th Century↗
PubMed1999

Atrial fibrillation early postoperatively following minimally invasive cardiac valvular surgery.

We report a cohort of our first 100 minimally invasive cardiac valvular operations matched 1:1 by age and valvular surgery type with patients undergoing a traditional midline sternotomy approach. The prevalence of postoperative atrial fibrillation among patients with minimally invasive procedures versus traditional midline sternotomy was 26.3% versus 38.0%, respectively (p = 0.08). Neither multiple logistic regression nor Kaplan-Meier distribution analysis identified differences in postoperative atrial fibrillation between the 2 surgical techniques.

Adult↗
PubMed1999

Insulin-like growth factors and IGF-binding proteins in bovine seminal plasma.

Insulin-like growth factor-I (IGF-I) is an important factor for germ cell development and maturation of spermatozoa. Actions of IGFs are modulated by IGF-binding proteins (IGFBPs) that may, depending on their concentration and site of expression, inhibit or enhance effects of IGF-I. We characterized IGFs and IGFBPs in seminal plasma from bulls routinely used for artificial insemination (AI) and from bulls producing poor-quality semen (low mass and individual motility of spermatozoa). IGFs were measured by specific radioimmunoassay in 22 samples of seminal plasma from nine different AI bulls with high (> 76.8%), average (72.8-73.4%), or low (< 69.5%) nonreturn rate (NRR). IGF-I and IGF-II levels were 144 +/- 9 ng/ml (mean +/- SE; range, 79-238 ng/ml) and 144 +/- 10 ng/ml (range, 55-221 ng/ml), respectively, and did not correlate with NRRs. IGF-I concentrations in seminal plasma from bulls producing poor-quality semen (n = 10) were significantly (P < 0.05) greater (194 +/- 26 ng/ml; range, 94-370 ng/ml), whereas IGF-II levels were significantly (P < 0.05) lower (93 +/- 17 ng/ml; range, 38-183 ng/ml) than in AI bulls. Ligand blot analysis of seminal plasma for IGFBPs revealed the presence of a 38-/45-kDa doublet band and a 30-kDa IGFBP. These IGFBPs were identified as IGFBP-3 and IGFBP-5, respectively, by immunoprecipitation using specific antibodies. In addition, a low amount of IGFBP-4 was detected in bovine seminal plasma by immunoprecipitation. There was a marked difference in the activity of IGFBPs between individual bulls, with a relatively small within-bull variance. The differences in IGFBP activities did not correlate with the fertilization capacity of the bulls in vivo or in vitro nor with immunoreactive IGF-I and IGF-II levels in seminal plasma. Our results demonstrate the presence of IGFBPs in bovine seminal plasma. In contrast to human seminal plasma, high activity of IGFBP-3 was detected in seminal plasma of some bulls, suggesting species-specific regulation of IGFBP activity by proteases.

Animals↗
PubMed1999

Limited proteolysis of the IGF binding protein-2 (IGFBP-2) by a specific serine protease activity in early breast milk.

IGF in milk possibly promote maturation of the gastrointestinal tract in newborns. We studied the composition of milk samples derived from 99 healthy women at regular intervals during a period beginning 3 d and ending 6 mo after birth. The concentrations measured by RIA on d 3 were 10.7+/-0.4 ng/mL for IGF-II, 1.9+/-0.1 ng/mL for IGF-I, 100+/-5 ng/mL for IGF binding protein-3 (IGFBP-3), and 2163+/-108 ng/mL for IGFBP-2. All factor concentrations decreased by up to 70% in the course of the 6 mo. The most striking finding was an IGFBP-2-specific protease activity. Protease assays performed by incubation of 125I-IGFBP-2 with milk yielded fragments of 14, 16, 23, and 25 kD. 125I-IGFBP-3 was not cleaved. Proteolysis occurred only in milk from mothers until 4 wk postpartum and could be visualized by immunoblots. Since the affinity of the fragments to 125I-IGF-II was low, they were not demonstrable by ligand blot. Inhibitor studies and pH optimizing classified the IGFBP-2 protease as an Me2(+)-dependent serine protease with a pH optimum of 7 to 8. The proteolytic activity of further milk proteins, known as IGFBP proteases, was analyzed. Epidermal growth factor receptor peptide and prostate-specific antigen did not cleave IGFBP-2, although the protease activity correlated (r = 0.84, p < 0.00003) with the prostate-specific antigen concentration in milk. The y-nerve growth factor cleaved 125I-IGFBP-2, but in a completely different manner than the milk protease. In conclusion, the IGFBP-2 protease in milk is most probably a kallikrein. The specific proteolysis of IGF/IGFBP-2 complexes may increase the biologic availability of IGF in early milk. This mechanism may promote growth of the maternal breast epithelium and maturation of the gastrointestinal tract of newborns.

Female↗
PubMed1999

Postnatal overexpression of insulin-like growth factor II in transgenic mice is associated with adrenocortical hyperplasia and enhanced steroidogenesis.

The influence of postnatal insulin-like growth factor II (IGF-II) overexpression on adrenal growth and function was investigated in 3-month-old male phosphoenolpyruvate carboxykinase (PEPCK) promoter human IGF-II transgenic mice, which are characterized by 4-to 6-fold elevated postnatal IGF-II serum levels. Plasma corticosterone levels of PEPCK-IGF-II transgenic mice were 2-fold higher than in age- and sex-matched controls, both in the morning (7.4 +/- 1.5 vs. 17.8 +/- 3.9 ng/ml, P < 0.01) and in the evening (33.3 +/- 6.5 vs. 65.3 +/- 12 ng/ml, P < 0.01). When PEPCK-IGF-II transgenic mice were subjected to an ACTH challenge, corticosterone levels were stimulated 6-fold, to 396 +/- 17 ng/ml after 60 min, compared with 230 +/- 24 ng/ml in the control group. In contrast to corticosterone, plasma ACTH levels were similar in transgenic and control mice, excluding an indirect effect of IGF-II at the hypothalamic or pituitary level. In vitro, the basal and ACTH-induced corticosterone production of adrenal glands from transgenic mice was higher (2-fold and 1.8-fold, respectively) than that of control organs. However, when normalized for adrenal weight, the in vitro corticosterone secretion was similar in both groups. At autopsy, adrenal weights of transgenic mice were significantly greater than those of control adrenal glands (3.3 +/- 0.2 vs. 2.0 +/- 0.2 mg, P < 0.01, n = 10). Furthermore, a local expression of human IGF-II could be demonstrated in transgenic adrenal glands by RT-PCR, whereas in normal adult mice, no adrenal expression of IGF-II was detected. Stereological investigation of adrenal glands from another set of PEPCK-IGF-II transgenic mice and controls (6-month-old males) demonstrated that the increase in adrenal weight in transgenic mice is mainly caused by a 50% increase in the number of zona fasciculata cells, whereas cell volume and zonation of transgenic adrenal glands remained unchanged. In conclusion, our data indicate that postnatal overexpression of IGF-II induces an increased adrenal weight and elevated corticosterone serum levels, presumably by a direct mitogenic effect of IGF-II on adrenocortical fasciculata cells.

Adrenal Glands↗
PubMed1999

Characterization of human insulin-like growth factor-binding proteins by two-dimensional polyacrylamide gel electrophoresis and Western ligand blot analysis.

The insulin-like growth factor (IGF)-binding proteins (IGFBPs) from adult human serum, amniotic fluid, and cerebrospinal fluid were analyzed by a modified two-dimensional gel electrophoresis followed by Western ligand blotting. The samples were subjected to immobilized pH gradient isoelectric focusing in the first dimension, followed by nondenaturing SDS-PAGE in the second dimension and autoradiography after ligand blotting with [125I]IGF-I or [125I]IGF-II. The identity of the binding proteins was confirmed by immunoblotting and immunoprecipitation with specific antibodies. Using this method, all six human high affinity IGFBPs could be clearly separated from each other according to their molecular mass and isoelectric points (pI). All IGFBPs exhibited a variety of specific pI isoforms, which presumably represent posttranslational modifications. In adult human serum, glycosylated IGFBP-3 is found as a broad band of spots with molecular masses of 41 and 45 kDa and a pI in the range of 4.8-8.2. The two IGFBP-3 bands could be reduced to a single 36-kDa band after deglycosylation (pI 6-9). Furthermore, the specific spots for IGFBP-2 (33 kDa; pI 6.2-7.1) and deglycosylated IGFBP-4 (24 kDa; pI 6.3, 6.5, and 6.8) were found with their expected molecular masses. Additionally, the diffuse bands around 30 kDa, found in one-dimensional Western ligand blotting, could be clearly separated into distinct groups of specific spots representing IGFBP-1 (30 kDa; pI 4.0-4.8), IGFBP-6 (30 kDa; pI 4.8-5.8), glycosylated IGFBP-4 (29 kDa; pI 6.1 and 6.3), and IGFBP-5 (30/31 kDa; pI 6.4-8). As expected, IGFBP-6 was visible only when IGF-II was used as radioligand. In conclusion, two-dimensional gel electrophoresis followed by Western ligand blotting allows identification of all six high affinity IGFBPs with their isoforms on the basis of their characteristic molecular masses and pI, especially in the range of 30 kDa. This technique can be rapidly performed with small amounts of complex biological fluids and is a powerful tool for the detection and analysis of posttranslational modifications of IGFBPs.

Adult↗
PubMed1998

[Social medicine expert assessment of post-traumatic stress disorder].

The concept of a posttraumatic stress disorder (PTSD) has become important for psychiatric diagnosis and research, particularly following US-american studies on Vietnam war veterans. Recently, studies on traindrivers involved in suicide accidents have shown symptoms of anxiety and depression in more than 30% of concerned drivers and typical symptoms of a PTSD in 15%. Here, we present the case of a traindriver who was involved in 6 suicide accidents within 17 years of traindriving (the average is 2 suicide accidents). Following the 3rd accident, the driver developed increasingly symptoms like anxiety, sleep disturbances, flashbacks and irritability. Following the 6th accident, he has been unable to work. A former expert opinion saw no relationship between the symptoms of the driver and the suicide accidents. Therefore, further information about the concept of a PTSD seems necessary to ensure early psychotherapeutic and pharmacological treatment of patients with such a disorder.

Accidents, Traffic↗
PubMed1998

Altered growth of mice divergently selected for body weight is associated with complex changes in the growth hormone/insulin-like growth factor system.

Mice investigated in this study were generated by selecting a sub-population of the NMRI out-bred stock (C), for high (H) or low (L) 8-week body weight. After 58 generations of selection, 8-week body weights of the sub-populations were markedly different if compared to controls. To investigate endocrine changes causing the altered growth performance in the different lines of mice, we analysed several components of the growth hormone (GH)/insulin-like growth factor (IGF) system. Pituitary weights of male and female L mice were significantly smaller than those of C and H mice. Relative to body weight, pituitary weights of male mice from the three lines did not differ, however pituitary weight-to-body weight-ratios of female L mice were significantly greater than those of H females. Mean volume densities of somatotropic cells were significantly smaller in L mice than in C and H mice. Serum IGF-I concentrations were significantly lower in the L line than in the C and H lines. H mice displayed significantly increased serum insulin levels both after ad libitum feeding and after a 14 hour fasting period. Ligand blot analysis of serum IGF-binding proteins (IGFBPs) revealed a significant reduction of circulating IGFBP-3 in L mice as compared to C and H mice. In contrast, serum IGFBP-2 mRNA levels were significantly increased in male L mice and showed non significant increases in female L mice. Hepatic IGFBP-2 mRNA levels were significantly increased in L mice and decreased in H mice as compared to C mice. Expression of IGFBP-4 mRNA in the liver was significantly decreased in both selection lines (L, H) as compared to the random-bred controls. Our findings demonstrate that altered growth of mice resulting from selection for body weight is associated with complex changes in the endocrine network of the GH/IGF system.

Adipose Tissue↗
PubMed1998

Surgical therapy for heart failure: care of the patient with partial left ventriculectomy.

Partial left ventriculectomy (PLV) surgery has gained significant attention worldwide as a possible alternative to heart transplantation or as a therapy to treat heart failure. This procedure offers an attractive choice to patients and physicians because of the lack of need for immunosuppressive medications and a decrease in the risk of rejection associated with transplantation. PLV surgery is currently under investigation in several centers worldwide, but long-term outcomes have yet to be definitively evaluated. The Cleveland Clinic Foundation began performing PLV surgery in May 1996. Since that time, 57 patients have received the procedure with actuarial survival of 82% at 1 year. The purpose of this article is to highlight the clinical management of the postoperative PLV patient.

Cardiac Output, Low↗
PubMed1998

Regulation of steroidogenesis by insulin-like growth factors (IGFs) in adult human adrenocortical cells: IGF-I and, more potently, IGF-II preferentially enhance androgen biosynthesis through interaction with the IGF-I receptor and IGF-binding proteins.

Although the effect of insulin-like growth factors (IGFs) in fetal adrenocortical cells has been investigated extensively, the role of the IGF system in the adult human adrenal gland remains unclear. In the present study we investigated the effect of recombinant human IGF-I and IGF-II on cortisol, dehydroepiandrosterone sulfate (DHEA-S) and cAMP synthesis in adult human adrenocortical cells in primary culture. Both IGFs stimulate basal as well as adrenocorticotropin (ACTH)-induced steroid secretion in a time- and dose-dependent fashion. While both IGFs (6.5 nM) induced only a moderate 2-fold increase in basal cortisol output after 48 h, the effect on basal DHEA-S secretion was significantly stronger, with a 2.7- and 3.7-fold stimulation by IGF-I and IGF-II respectively. Similarly, IGF-II enhanced ACTH-induced cortisol and DHEA-S secretion more potently than IGF-I. In dose-response experiments, the maximum stimulation of ACTH-induced DHEA-S secretion was induced by 1.6 nM IGF-I (2-fold increase) or IGF-II (2.9-fold increase), while the maximum response of cortisol secretion was elicited only at 13 nM IGF-I (2-fold increase) or IGF-II (2.5-fold increase). This resulted in a significant shift of the DHEA-S dose-response curves to the left, indicating a relative selective stimulation of androgen biosynthesis by physiologically low concentrations (0.4-3.2 nM) of IGF-II, and less potently by IGF-I. At all doses tested, the steroidogenic effect of IGF-II was significantly stronger than the effect of IGF-I. Although both IGF receptors are present in adult human adrenocortical cells, the steroidogenic effect of IGF-II is mediated through the IGF-I receptor, since [Arg54,55]IGF-II, which only binds to the IGF-I receptor, was equipotent with native IGF-II, whereas [Leu27]IGF-II, which preferentially binds to the type II IGF receptor, did not show any effect. In addition, [des1-3]IGF-I, which exhibits only minimal binding to IGFBPs, was significantly more potent than native IGF-I in stimulating adrenal steroid biosynthesis, and elicited almost the same maximum stimulatory effect as IGF-II and [des1-6]IGF-II. By Western ligand blotting of conditioned medium it was shown that adult human adrenocortical cells secrete various IGF-binding proteins (IGFBPs), which are induced differentially by treatment with ACTH. In conclusion, these results demonstrate that: (1)IGF-II stimulates basal as well as ACTH-induced DHEA-S and cortisol secretion from adult human adrenocortical cells more potently than IGF-I; (2) both IGFs predominantly stimulate androgen biosynthesis; (3) the steroidogenic effect of IGF-I and IGF-II is mediated through interaction with the IGF-I receptor; (4) the different steroidogenic potency of IGF-I and IGF-II might be explained by interaction of these ligands with locally produced IGFBPs. These data indicate that the IGF system plays an important role in the regulation of the differentiated function of adult human adrenocortical cells.

Adrenal Cortex↗
PubMed1998

Neonates making the transition from intensive care to home care.

Premature infants are a very fragile group of patients. Providers that propose to care for them need to understand their special risks--as well as the risks such care poses to agencies themselves. Solid preparation, however, can result in success for both infants and agencies.

Community Health Nursing↗
PubMed1997

[The forensic-psychiatric evaluation of young persons in accordance with 105 JGG between punishment and therapeutic help].

105 of the the German Jugendgerichtsgesetz (JGG, law on criminal cases involving offenders between 14 and 17 years of age) allows the use of this special law also for offenders between 18 and 21 years of age if they can be considered juveniles with regard to their personal development or the type of crime they have committed. Assessment of the "maturity" of young people in this age group has been the subject of great controversy in forensic psychiatry since the first JGG went into effect in 1953. In spite of numerous attempts to operationalize the term "Jugendlicher", for example in the Marburg guidelines, it has not yet been possible to establish clear-cut criteria defining the characteristics of those who are juveniles in the sense of the JGG. Neither child and adolescent psychiatry nor criminal law nor criminology has provided an adequate basis for such a definition. The wide range of discretionary decisions in forensic psychiatry and the associated lack of legal uniformity may, however, be a necessary prerequisite for an adequate assessment of an individual case. Although the chances of a change in criminal law governing those between 18 and 21 are small, creation of a law specifically for this age group, with a separation of the educational-therapeutic aspects from the punishment aspects, could be a great help to those preparing expert opinions in forensic psychiatry and to the juvenile courts because it would necessitate greater clarity in decisions relating to this group of offenders. Elimination of Section 105 JGG and the subsequent use of either general criminal law or that governing those under age 18 only, which has been proposed repeatedly, is not recommended.

Adolescent↗