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Biomedical subjects

G Steinmann

Publications and source records attributed to G Steinmann.

At least 19 recordsLinked to original sources
PubMed2003

Adult presentation of MCAD deficiency revealed by coma and severe arrythmias.

We report the case of a 33-year-old man who presented with headaches and vomiting. Soon after admission he became drowsy and agitated, developed ventricular tachycardia and his neurological state worsened (Glasgow coma score 6). Blood analysis showed respiratory alkalosis, hyperlactacidemia (8 mmol/l), hyperammonemia (390 micro mol/l) and hypoglycaemia (2.4 mmol/l). Subsequently, he developed supraventricular tachycardia, ventricular tachycardia and ultimately ventricular fibrillation resulting in cardiac arrest, which was successfully treated. A CT scan of the head revealed cerebral oedema. Whilst in the intensive care unit, he developed renal failure and rhabdomyolysis. The metabolic abnormalities seen at the time of admission normalised within 48 h with IV glucose infusion. Biological investigations, including urinary organic acids and plasma acylcarnitines, showed results compatible with MCAD deficiency. Mutation analysis revealed the patient was homozygous for the classical mutation A985G. This is one of only a few reports of severe cardiac arrhythmia in an adult due to MCAD deficiency. This condition is probably under-diagnosed in adult patients with acute neurological and/or cardiac presentations.

Acyl-CoA Dehydrogenase↗
PubMed2001

Absence of efficacy of subcutaneous antisense ICAM-1 treatment of chronic active Crohn's disease.

BACKGROUND & AIMS: ISIS-2302, an antisense oligonucleotide directed against intercellular adhesion molecule 1, was effective in steroid refractory Crohn's disease in a pilot trial. The aim of this study was to investigate safety and efficacy of ISIS-2302 in chronic active Crohn's disease (CACD). METHODS: A dose-interval, multicenter, placebo-controlled trial was conducted in 75 patients with steroid-refractory CACD (Crohn's Disease Activity Index [CDAI], 200-400). The primary endpoint was steroid-free remission (CDAI <150) at week 14. RESULTS: Only 2 of 60 (3.3%) ISIS-2302-treated and no placebo patients reached the primary endpoint. Steroid-free remission at week 26 (secondary endpoint) was reached in 8 of 60 (13.3%) active treatment and 1 of 15 (6.7%) placebo patients. A greater proportion of ISIS-2302-treated than placebo patients achieved a steroid dose <10 mg/day at weeks 14 and 26 (48.3% vs. 33.3% and 55.0% vs. 40.0%, respectively, and a glucocorticoid dose of 0 mg [prednisone equivalent] at week 26 [23.3% vs. 6.7%, respectively]). Treatment with ISIS-2302 was safe. The most common side effects were injection site reactions in the active treatment group (23% in ISIS-2302-treated patients vs. none in placebo patients). No statistically significant differences in the frequency of side effects were detected between dose groups. CONCLUSIONS: The trial did not prove clinical efficacy of ISIS-2302 based on the primary endpoint. Positive trends were observed in some of the secondary endpoints.

Adult↗
PubMed1999

Isolated limb perfusion with tumour necrosis factor-alpha and melphalan with or without interferon-gamma for the treatment of in-transit melanoma metastases: a multicentre randomized phase II study.

This open, multicentre, randomized phase II trial was conducted to determine the effect of isolated limb perfusion (ILP) with tumour necrosis factor-alpha (TNFalpha) in combination with melphalan with or without interferon-gamma (IFNgamma) in patients with in-transit metastases of melanoma of the limbs (MD Anderson stage IIIA or IIIAB, AJCC stage III). The 64 patients included were randomized to receive either a two- drug regimen consisting of TNFalpha and melphalan (TM-ILP) or a three-drug regimen consisting of TNFalpha, melphalan and INFgamma (TIM-ILP). Patients randomized to receive IFNgamma were pretreated for 2 days before the ILP with once daily 0.2 mg IFNgamma subcutaneously and also received the same amount of IFNgamma during ILP. A total of 47 complete responses (73%) were reported, 22 (69%) of which occurred in the TM-ILP group and 25 (78%) in the TIM-ILP group; the difference was not significant. The 14 partial responses (22%) were split evenly between the treatment groups. In the TM-ILP group, two cases of stable disease and one case of progressive disease were reported. The overall response rate (complete plus partial responses) was 100% in the TIM-ILP group and 91% in the TM-ILP group, yielding an overall response of 95% for this study. In the historical control data, where 103 patients had received melphalan alone (M-ILP), there were 54 records of complete responses (52%) and 80 of complete or partial responses (78%). The median survival time estimated by the Kaplan-Meier method was 819 days for the TM-ILP group, > 705 days for the TIM-ILP group and 873 days for the combined study population; estimates for time to local progression or recurrence were 327 days, in excess of 498 days and 405 days, respectively. The corresponding figure for the historical controls was 338 days. These data suggest that TNFalpha associated with melphalan may be superior to melphalan alone for ILP.

Adult↗
PubMed1998

A model on the escape from the Malthusian trap.

"We propose a model to capture the escape from the Malthusian trap in the longrun. Our aim is to emphasize the key role of endogenous technological progress--as initiated by population growth and education--for longrun economic development. In addition we stress the importance to consider the level of fertility and mortality as the determinants of economic development and not only the rate of population growth. In particular, we may observe different economic growth rates in countries with the same rate of population growth, but differing levels of birth and death rates."

Demography↗
PubMed1994

On a causal mechanism of chronic thymic involution in man.

The age-associated chronic thymus involution is interpreted to occur due to cytolytic depletion of thymic stromal tissue whose cells present altered self-peptides. Using simplified assumptions and based on morphometric data on thymic involution in man, the chance for a single protein to be altered is estimated to be in the range of 2-4 x 10(-6) per year. The corresponding mutation rate is compatible with that derived from both evolutionary and direct studies, thus supporting the proposed model.

Adolescent↗
PubMed1991

Population growth, farmland, and the long-run standard of living.

"This paper studies the natural-resources element in the theory of population growth over the very long run. In the context of the stock of land and Malthusian crises in earlier times, the model shows how resources have become more available rather than more scarce, even as population and income have increased. The paper sketches a mechanism which added to the Malthusian system, leads to entirely different conclusions than does the Malthusian system.... That is, population growth creates new problems which in the short run constitute additional burdens which, in the longer run, lead to new developments that leave people better off than if the problems had never arisen." This is a revised version of a paper originally presented at the 1989 Annual Meeting of the Population Association of America (see Population Index, Vol. 55, No. 3, Fall 1989, p. 382).

Agriculture↗
PubMed1988

Population growth and economic development in the very long run: a simulation model of three revolutions.

The authors propose an economic model capable of simulating the 4 main historical stages of civilization: hunting, agricultural, industrial, and postindustrial. An output-maximizing society to respond to changes in factor endowments by switching technologies. Changes in factor proportions arise through population growth and capital accumulation. A slow rate of exogenous technical process is assumed. The model synthesizes Malthusian and Boserupian notions of the effect of population growth on per capita output. Initially the capital-diluting effect of population growth dominates. As population density increases, however, and a threshold is reached, the Boserupian effect becomes crucial, and a technological revolution occurs. The cycle is thereafter repeated. After the second economic revolution, however, the Malthusian constraint dissolves permanently, as population growth can continue without being constrained by diminishing returns to labor. By synthesizing Malthusian and Boserupian notions, the model is able to capture the salient features of economic development in the very long run.

Agriculture↗
PubMed1985

On the optimum theoretical rate of population growth.

"The paper seeks intuitively-satisfying models of optimum population growth. The authors build upon Phelps's model of endogenous technical progress plus the Steinmann-Simon extension, which imply that the per-person consumption growth rate depends positively and linearly upon the population growth rate, without bound.... They suggest that the consumption rate ultimately turns downwards as population growth increases because of decreasing adoption of available technology as labor cheapens relative to capital, and as high population growth overtaxes people's will and ability to respond. Including a convex-downward function in the model yields sensible results." (summary in GER)

Demography↗
PubMed1983

Serological visualization of interleukin 2.

Interleukin 2, a lymphokine that acts as a second signal of cellular immune response by way of its action as a T-cell growth factor, was morphologically identified by immunoperoxidase staining. With the use of a monoclonal antibody to interleukin 2 and several complex-forming antisera, the lymphokine was readily distinguished in cytocentrifuge preparations of peripheral blood leukocytes stimulated with a T-cell mitogen. When preparations of cloned interleukin 2 producer and responder cells were stained by the same procedures, discrete patterns of both responder and producer cell phenotypes were revealed. Interleukin 2 producer T cells exhibited a characteristic intense, ringlike cytoplasmic staining, whereas the responder cells (as exemplified by interleukin 2-dependent cell lines) exhibited a less intensive, spotlike membrane staining. In addition, intense membrane localization of interleukin 2, reminiscent of potential capping phenomena, could be observed in stained preparations of cloned responder cells.

Animals↗
PubMed1983

Malignant lymphoma of plasmacytoid T-cells. Morphologic and immunologic studies characterizing a special type of T-cell.

In 1958, a medium-sized cell was recognized in human lymph nodes and found to occur in clusters in about one out of every 10 cases of reactive hyperplasia. At first, it was interpreted as a lymphoblast. Later, electron-microscopic investigations revealed that the cell contained abundant rough endoplasmic reticulum and was apparently restricted to T-regions of lymph nodes. Recently, it was possible to analyze a malignant lymphoma uniformly composed of such cells with a panel of monoclonal antibodies. The cells proved to be Leu-1+, OKT4+, Leu-3a+, HLA-DR+, and weakly reactive with VIL-A1 (antibody to common ALL antigen) and clone F8-11-13, but negative for OKT3, OKT11, OKT8, cytoplasmic immunoglobulin, common B-cell antigen, and C3b receptors. Short-term, in vitro cultures of lymphoma cells showed weak responses to phytohemagglutinin and Interleukin 2 (IL2), but no IL2 production. Lymphoma cells had a low spontaneous proliferation rate (about 2% Ki-67+ cells). In view of these findings, the term "plasma-cytoid T-cell" is proposed. A functional relationship between these cells and the myeloid system was suggested because the patient developed a myelomonocytic leukemia 3 months after the diagnosis of malignant lymphoma was made.

Aged↗
PubMed1982

Immuno-electron microscopic tracing of lactoferrin, a regulator of myelopoiesis, into a subpopulation of human peripheral blood monocytes.

Lactoferrin (LF), an iron binding glycoprotein present in the specific granules of mature granulocytes, is capable of suppressing the production of granulocyte-macrophage colony stimulatory factors (GM-CSF) by monocytes and macrophages in vitro and rebound myelopoiesis in vivo. By an immuno-electron microscopic technique (peroxidase-antiperoxidase procedure) in combination with a three-step fixation and detergent treatment of mononuclear blood cells pulsed with LF, intracellular localization of LF in a sub-population of human monocytes with a well-preserved subcellular morphology was demonstrated. LF was found in the monocytes after a 30 min pulse with concentrations of LF as low as 10(-14) M. Under the electron microscope, deposits of approximately 110 nm diameter appeared scattered in the area of the endoplasmic reticulum. Large numbers of smaller deposits (20-70 nm) were found in the euchromatin. The heterochromatin and other cytoplasmic organelles were free of LF. These results suggest that the euchromatin might be the functional site for LF inhibition of the production of GM-CSF by a subpopulation of human monocytes.

Cytoplasmic Granules↗
PubMed1982

Morphologic findings in lymph nodes after occlusion of their efferent lymphatic vessels and veins.

Cervical lymph nodes of rabbits were congested for 24 hours, 7 days, and 14 days by occlusion of the nodal veins, efferent lymphatics, or both. The lymph nodes were examined by histologic and morphometric methods, and the results were compared with findings in control nodes. The present study demonstrated that the vascular sinus transformation (VST), observed first in human lymph nodes, is reproducible experimentally. Complete occlusion of both the veins and lymphatics led to a marked increase in volume of the nodes and often to total necrosis of their parenchyma. Incomplete occlusion of the veins combined with complete occlusion of the lymphatics or complete occlusion of the lymphatics alone resulted in VST as early as 7 days after the operation. In the first stage of VST, proliferation of the subendothelial tissue accompanied by proliferation of blood capillaries was noted. The proliferation started from the capsular side of the marginal sinus and from the trabecular side of the intermediate sinuses. Subsequently, the sinuses transformed into a framework of channels resembling blood capillaries. Without occlusion of the efferent lymphatics, VST did not develop. Complete or incomplete occlusion of the veins combined with complete occlusion of the lymphatics resulted in a pronounced thickening of the capsule, sclerosis of the medullary sinuses, depletion of lymphocytes in the nodal parenchyma, and cavernous dilation of the medullary sinuses. After occlusion of the lymphatics alone these changes were less extensive. Occlusion of veins alone caused only moderate thickening of the capsule and slight sclerosis of nodal parenchyma, but no VST. Total necrosis of the parenchyma occurred only after combined complete occlusion of nodal veins and lymphatics.

Animals↗
PubMed1981

T-cell growth factor (interleukin 2) and terminal transferase activity in human leukemias and lymphoblastic cell lines.

Mononuclear blood cells from patients with different types of leukemia, and from controls as well as cells from established lymphoblastic cell lines were analyzed with respect to terminal transferase (TdT) activity and T-cell growth factor (TCGF; Interleukin 2, IL-2), to determine the significance of TCGF production and response as functional markers for human leukemias. The data obtained so far suggest that the aberrant proliferation and lack of maturation observed in these leukemias may be associated with or be the result of a break-down in cellular-mediated control of proliferation.

Acute Disease↗
PubMed1981

T- and B-cell responses in patients with malignant pleural effusions.

Lymphocytes of lymphocyte-rich pleural effusions and venous blood from 16 cancer patients, 7 patients with benign pleural effusions and blood from 23 normal blood donors, were examined for cytological features, rosette-forming capacity, immunofluorescent staining, and PHA-stimulated DNA synthesis. Total protein and immunoglobulin levels were also determined. Metastatic effusions revealed approximately 40% higher content of immunoglobulins G, A and M (P less than 0.002) as well as of total protein (P less than 0.005) than non-metastatic pleural effusions. However, the serum of the non-cancer patients contained approximately 50% higher level of Ig than in cancer patients (P less than 0.001). Whilst there was no significant difference in the relative T- or B-cell contents of pleural effusions between cancer and non-cancer patients (P greater than 0.05) spontaneous proliferation of lymphocytes was significantly increased (P greater than 0.01), which led to a lower PHA-stimulated transformation index in pleural effusions from cancer patients than in all other lymphocyte sources examined (P less than 0.001).

Adult↗