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Biomedical subjects

A F Muller

Publications and source records attributed to A F Muller.

At least 55 records · Page 3Linked to original sources
PubMed1992

Splenic function in alcoholic liver disease.

Splenic function was assessed in 42 patients with alcoholic liver disease by counting the percentage of erythrocytes with indentations or pits, seen by differential interference contrast microscopy. These pits represent cellular debris normally removed by the spleen. The findings were compared with 42 age and sex matched controls. Mean (SEM) pitted red cell counts in the patients was 2.7 (0.4)% and in the controls 0.7 (0.07)% (p < 0.001). In all of the eight reformed drinkers (five with biopsy proven cirrhosis), cell counts were normal. Six patients with alcoholic liver disease had had serious infections within the past year. Of these, one had had a recent pneumococcal pneumonia and another of the patients died from overwhelming pneumococcal septicaemia. Both of these patients had evidence of functional hyposplenism as judged by high pitted erythrocyte counts. A total of 18 patients were considered to have pitted red cell counts above the normal, and 11 of these had proven cirrhosis and/or gross ascites. This study is the first to show the presence of functional hyposplenism in alcoholic liver disease and provides further evidence of the predisposition that these patients have to infection. At present, it is unclear whether the hyposplenism is a direct toxic effect of alcohol or the result of cirrhosis; further studies are warranted.

Adult↗
PubMed1992

Role of duplex Doppler ultrasound in the assessment of patients with postprandial abdominal pain.

In 10 patients with postprandial abdominal pain thought likely to be the result of mesenteric ischaemia Doppler ultrasound examinations of the superior mesenteric and coeliac arteries were performed both after fasting and a standard meal of 800 kcal. Compared with control values Doppler waveform analysis suggested seven abnormal vessels. Two patients had abnormal fasting superior mesenteric artery waveforms manifested by very high peak systolic velocities together with spectral broadening (one also had evidence of coeliac artery stenosis), and one patient had normal velocities but an abnormal signal and evidence of proximal superior mesenteric stenosis was supported by colour Doppler imaging and confirmed by angiography. Postprandially, two patients showed very high peak systolic and end diastolic velocities in the superior mesenteric artery (one had had a normal fasting waveform signal) and one in the coeliac artery, suggestive of vascular stenosis, while one patient showed a fall in peak systolic velocity. The diagnosis of mesenteric ischaemia in two of these patients was supported by digital subtraction angiography and abdominal computed tomography. Doppler ultrasound may be a useful non-invasive investigation for patients with postprandial abdominal pain that helps to select patients for angiography. Patients with tight vascular stenosis may have abnormal fasting Doppler waveform patterns but in symptomatic patients further information may be obtained after the haemodynamic stress of feeding. Additional information to enhance the diagnostic sensitivity of the test may be obtained by colour Doppler imaging.

Abdominal Pain↗
PubMed1992

Regional blood flow in chronic heart failure: the reason for the lack of correlation between patients' exercise tolerance and cardiac output?

BACKGROUND: In patients with chronic heart failure there is no relation between cardiac output and symptom limited exercise tolerance measured on a bicycle or treadmill. Furthermore, the increase in cardiac output in response to treatment may not be matched by a similar increase in exercise tolerance. More important in determining exercise capability is blood flow to skeletal muscle. This implies that the reduction in skeletal muscle blood flow is not directly proportional to the reduction in cardiac output and that there are regional differences in blood flow in patients with heart failure. METHODS: Cardiac output and regional blood flow measured in 30 patients with chronic heart failure were compared with values obtained from 10 healthy controls. Measurements were made at rest and in response to treadmill exercise and were all made non-invasively. RESULTS: Cardiac output was lower in the patients at rest and during exercise. Blood flow in the superior mesenteric and renal arteries was also lower in the patients and represented a different proportion of cardiac output than in the controls. In response to exercise the increase in blood flow to the calf and therefore to skeletal muscle, was reduced in the patients. In the patients there was no correlation between resting cardiac output and blood flow in the superior mesenteric artery, renal artery, or calf. CONCLUSIONS: Because blood flow to skeletal muscle and to the kidneys is likely to be important in determining patients' symptoms this factor may explain why central haemodynamic variables do not correlate with the exercise tolerance in patients with chronic heart failure.

Aged↗
PubMed1992

The integrated response of the cardiovascular system to food.

To obtain information about the integrated response of the cardiovascular system to food, cardiac output and regional blood flow (superior mesenteric artery, renal artery and calf blood flow) were measured in 14 normal young healthy subjects after an overnight fast and following a standard 800-kcal meal. Results were compared with 8 subjects who remained fasted throughout the study. Cardiac output increased from a mean (SEM) fasting value of 4.8 (0.3) l/min to a peak after 30 min of 6.1 (0.5) l/min (p < 0.001). Superior mesenteric blood flow increased from a fasting value of 463 (45) to a peak of 854 (110) ml/min also after 30 min (p < 0.001). These changes were accompanied by a significant fall in both systemic vascular resistance and superior mesenteric vascular resistance (p < 0.001). Only at the 15-min postprandial measurements was there a significant relationship between the increase in cardiac output and superior mesenteric artery blood flow (r = 0.62, p = 0.02). Calf blood flow increased and vascular resistance fell postprandially (p < 0.05), but there was little change in right renal artery blood flow. There was an insignificant fall in renal vascular resistance. Heart rate increased from a resting value of 65 (3) to a peak of 77 (4) beats/min after 15 and 30 min (p < 0.001), diastolic blood pressure fell postprandially with little change in systolic blood pressure. These results suggest that in healthy young subjects the increase in gut blood flow is met by an increase in cardiac output, with little evidence of redirection from other vascular beds. The early postprandial increase in superior mesenteric blood flow may account for the increase in cardiac output, although the magnitude of the change is much greater for cardiac output than superior mesenteric artery blood flow.

Adult↗
PubMed1991

Exercise capability in heart failure: is cardiac output important after all?

The exercise capability of 39 patients with severe chronic heart failure was assessed in several ways and compared with measurements of cardiac output. The relation between cardiac index and exercise tolerance measured on a treadmill was poor (r = 0.191, p = 0.245). However, exercise tolerance measured with a series of self-paced corridor walk tests showed moderate correlations with cardiac index (r = -0.404, p = 0.015 to r = -0.516, p = 0.001) and customary activity assessed by step counting correlated better with cardiac index (r = 0.537, p less than 0.001). Cardiac output therefore seems to be a factor determining patients' exercise capability when they choose their own walking speed but not when they undergo formal treadmill tests in the laboratory.

Aged↗
PubMed1991

The MELANIE project: from a biopsy to automatic protein map interpretation by computer.

The goals of the MELANIE project are to determine if disease-associated patterns can be detected in high resolution two-dimensional polyacrylamide gel electrophoresis (HR 2D-PAGE) images and if a diagnosis can be established automatically by computer. The ELSIE/MELANIE system is a set of computer programs which automatically detect, quantify, and compare protein spots shown on HR 2D-PAGE images. Classification programs help the physician to find disease-associated patterns from a given set of two-dimensional gel electrophoresis images and to form diagnostic rules. Prototype expert systems that use these rules to establish a diagnosis from new HR 2D-PAGE images have been developed. They successfully diagnosed cirrhosis of the liver and were able to distinguish a variety of cancer types from biopsies known to be cancerous.

Biopsy↗
PubMed1991

Post-prandial worsening of angina: all due to changes in cardiac output?

BACKGROUND: The precise mechanism leading to the post-prandial worsening of angina has yet to be adequately defined. It has been attributed to an increase in double product but is perhaps more likely to be related to an increase in cardiac output after food. This study was designed to evaluate the effects of food on patients' exercise tolerance and compare these with changes in haemodynamic variables. METHODS: 23 patients with chronic stable angina who had post-prandial worsening of their angina were studied. The patients were evaluated on two occasions and at each visit they underwent two symptom limited treadmill exercise tests. They remained fasting on the first visit and were given a 1400 kcal meal 60 minutes before the second exercise test on the second visit. Time to onset of 1 mm ST segment depression, heart rate, systemic arterial blood pressure, and cardiac output were measured at rest and during exercise. RESULTS: There were no differences in any of the variables during the two exercise tests on the day the patients remained fasting. After the meal exercise tolerance fell significantly by 136 seconds and the stage at which 1 mm ST segment depression was first seen was also significantly reduced. Resting cardiac output increased significantly by 0.86 1/min with the patients sitting and by 0.89 1/min standing. The exercise times after food were significantly related to cardiac output even when fasting times were taken into account. Resting heart rate increased significantly by 8.3 beats per minute sitting and 10.4 beats per minute standing. There was little change in blood pressure and no evidence that the double product predicted the post-prandial exercise time. CONCLUSIONS: Worsening of angina was related to the increase in cardiac output after a meal and successful treatment will depend upon the prevention of this increase.

Aged↗
PubMed1991

Very severe self-poisoning lithium carbonate intoxication causing a myocardial infarction.

A case of severe lithium carbonate self-poisoning is described, presenting with a very high serum lithium level (14.6 mmol/L) on admission. Lengthy and repeated hemodialyses were required to lower lithemia to nontoxic ranges. As is usually reported, our patient had prolonged neurologic manifestations (coma, hyperreflexia, fluctuating focal signs) and developed hypotension, cardiovascular collapse, nephrogenic diabetes insipidus, and diarrhea. Other less common features were the occurrence of acute myocardial infarction without coronary artery lesions and thrombocytopenia. The possible pathogenic mechanisms are discussed. Hemodialysis and supportive intensive care treatment are commented upon. The final outcome was favorable, and the patient recovered completely.

Bipolar Disorder↗
PubMed1990

Effects of enoximone in patients with heart failure uncontrolled by captopril and diuretics.

Ten patients with severe heart failure, symptomatic despite treatment with diuretics and captopril, completed a study of the effect of adding enoximone to their normal treatment. Enoximone or matching placebo was given for 4 weeks in randomized double-blind order following a single-blind placebo run-in period. Exercise capability was measured with two different treadmill protocols, a corridor walk test and by step-counting with body-worn pedometers. Cardiac output and limb blood flow were assessed non-invasively by measuring respiratory gases and by venous occlusion plethysmography. Measurements were made at rest and in response to treadmill exercise. The mean exercise tolerance measured using the modified Bruce treadmill protocol was increased from the placebo value (498 +/- 91 seconds) after both 2 weeks (573 +/- 94 seconds, P = 0.051) and 4 weeks of enoximone (572 +/- 100 seconds, P = 0.057). Enoximone increased exercise duration in fixed workload tests from the placebo value (252 +/- 75 seconds) after 2 weeks' treatment (431 +/- 98 seconds, P = 0.011) and after 4 weeks (381 +/- 85 seconds, (P = 0.01). The percentage improvement with the fixed workload test was greater than with the modified Bruce protocol at week 2 (P = 0.03) and at week 4 (P = 0.051). Enoximone increased the speed of walking 100 m at self-selected slow, normal and fast paces. It had little effect on customary activity of the patients. Enoximone increased cardiac output measured at rest and during submaximal exercise (P = 0.001). It also improved blood flow to the calf muscle at rest and after exercise (P = 0.01). Enoximone has a beneficial effect in chronic heart failure symptomatic despite treatment with diuretics and captopril. The magnitude of its effect, however, depends upon the technique used to assess it.

Aged↗
PubMed1990

Regional haemodynamic effects of captopril, enalaprilat and lisinopril in conscious water-replete and water-deprived Brattleboro rats.

1. The regional haemodynamic effects of intravenous bolus doses of captopril, enalaprilat and lisinopril were assessed in conscious Brattleboro (i.e. vasopressin-deficient) rats, chronically instrumented with miniaturized pulsed Doppler probes and intravascular catheters. 2. Responses to incremental doses of each drug (spanning the median effective dose for the inhibition of the pressor response to angiotensin I) were examined in both water-replete and water-deprived states. 3. In the water-replete state, the haemodynamic profiles of captopril, enalaprilat and lisinopril were generally similar, with incremental doses causing rises in mesenteric and renal flow and, to a lesser extent, hindquarters flow. There were small tachycardias and only slight falls in mean blood pressure. 4. In the water-deprived state, the effects of all three drugs were greatly enhanced; tachycardic and hypotensive effects occurred together with increases in mesenteric, renal and hindquarters flows. However, for renal flow and renal vascular conductance the effectiveness of the drugs decreased in the order enalaprilat greater than captopril greater than lisinopril, whereas for mesenteric flow and mesenteric vascular conductance the order was captopril greater than enalaprilat greater than lisinopril. 5. Since marked haemodynamic actions were seen with doses one-tenth of the median effective dose for the inhibition of the pressor effect of angiotensin I, it is likely these effects were due to inhibition of angiotensin-converting enzyme, although not necessarily to inhibition of angiotensin II production.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Regional distribution of neuropeptide Y-like immunoreactivity in human hypothalamus measured by immunoradiometric assay: possible influence of chronic respiratory failure on tissue levels.

The regional distribution of neuropeptide Y-like immunoreactivity (NPY-IR) in the human hypothalamus has been determined using a highly specific immunoradiometric assay. Hypothalami were removed during postmortem examination from 19 subjects. The pituitary stalk and 11 anatomically defined nuclei and areas were microdissected from one or both sides of each hypothalamus. NPY-IR was detectable in the acid extracts of tissue samples prepared from all the hypothalamic regions studied, with the highest concentrations being found in the infundibular nucleus (325 +/- 53 fmol/mg wet weight of tissue) and the ventromedial nucleus (217 +/- 22 fmol/mg). For the 11 subjects where both sides of the hypothalamus were dissected, values obtained for the areas in one half showed a good degree of symmetry with the corresponding areas on the contralateral side. The infundibular nucleus exhibited the greatest range of values (72-1,137 fmol/mg). Interestingly, variations in other parts of the hypothalamus were observed to parallel those of this nucleus. Expressed as correlation coefficients (r), levels in the infundibular nucleus appeared to be most closely related to those of the ventromedial nucleus (VM; r = 0.89) and paraventricular nucleus (PV; r = 0.84). In addition, retrospective analysis of the clinical histories showed that all patients with very high NPY levels in the infundibular nucleus (621.0 +/- 107.7 fmol/mg; n = 8) had suffered from respiratory failure or severe dyspnea of at least 10 days duration prior to death. The remaining patients (166.7 +/- 17.1 fmol/mg; n = 11) had either died 48 h from the onset of cardiorespiratory difficulties or of unrelated causes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Tumor necrosis factor alpha inhibits the hormonal response of the pituitary gland to hypothalamic releasing factors.

Tumor necrosis factor alpha (TNF alpha), a monokine produced by activated macrophages and monocytes, may be an essential mediator of the pathogenesis and of the hormonal response to endotoxic shock. It has been suggested that an elevated level of TNF alpha is a marker for morbidity and mortality during septic shock, and that treatment with antibodies against TNF alpha decreases mortality. Because monokines have been shown to interact at the hypothalamic-pituitary level, we have studied the effect of TNF alpha on basal and stimulated hormone release from normal rat anterior pituitary cells. After 3 days of incubation, primary cultures of rat anterior pituitary cells were stimulated with either 0.5 ng/ml CRF, 3 ng/ml AVP, 10 ng/ml angiotensin II (AII), 10(-6) M TRF, 10(-8) M LHRH, or 10(-8) M GHRH, alone or in the presence of 20 or 50 ng/ml human or murine recombinant TNF alpha. The culture media were analyzed for ACTH, GH, LH, and PRL content. Each experiment was performed in triplicate and was repeated 3 to 8 times. Time-course experiments (n = 3) demonstrated that TNF alpha inhibited CRF-stimulated ACTH production over a period of 8, 16, and 24 h, but had no effect before a period of 4 h. At doses ranging from 1 to 100 ng/ml, TNF alpha did not affect basal ACTH secretion but inhibited CRF-stimulated ACTH release in a dose-dependent manner (ED50 approximately 10 ng/ml). At a dose of 50 ng/ml, TNF alpha inhibited AVP-stimulated ACTH release by 30% and blocked the effect of AII. TNF alpha (20 and 50 ng/ml) completely prevented the CRF-AVP potentiation of ACTH release. Similarly, TNF alpha inhibited the stimulated release of GH (100% inhibition), LH (35% inhibition), and PRL (100% inhibition). TNF alpha had no effect on the basal secretion of GH or LH but inhibited basal PRL in a dose-dependent manner. The administration of the monokine did not cause any cellular damage because 48 h after removal of the TNF alpha treatment the cells showed normal basal and stimulated hormone levels in response to their specific stimuli. Incubation of TNF alpha solutions with antibody to TNF alpha reversed all TNF alpha actions. These data suggest that TNF alpha inhibits the secretion of pituitary hormones and particularly suppresses the response of the corticotroph cells. This inhibitory effect may contribute to the increased mortality observed in cases of severe septic shock with high circulating TNF alpha levels.

Adrenocorticotropic Hormone↗
PubMed1989

Specific effect of CV 205-502, a potent nonergot dopamine agonist, during a combined anterior pituitary function test.

CV 205-502, an octahydrobenzo[g]quinoline, is a dopamine agonist compound that is not an ergot or ergoline derivative. To investigate the site of action of CV 205-502, three groups of five men were given single daily doses of CV 205-502 (0.04, 0.06, or 0.08 mg/day, doses that suppress plasma PRL by 60-80% for 24 h) for 5 days; on day 6 a combined anterior pituitary function test using iv administration of four hypothalamic releasing hormones (TRH, 200 micrograms; GHRH, 100 micrograms; CRH, 100 micrograms; LHRH, 100 micrograms) was performed. One month later the challenge tests were repeated to obtain control values. The following hormones were measured by RIA in plasma: TSH, ACTH, cortisol, PRL, GH, LH, FSH, and testosterone. With the exception of plasma PRL levels, basal and releasing hormone-stimulated values were similar after CV 205-502 administration and after the 1-month washout period. Basal plasma PRL was lower after CV 205-502 administration, and the response to TRH was attenuated by all three doses of CV 205-502 (the mean percent inhibition values were 76%, 93%, and 94%, respectively). All three doses of CV 205-502 were well tolerated, and another group of men well tolerated 0.1 mg daily. The results confirm that CV 205-502 is a potent dopamine agonist, which directly inhibits lactotropic cells but has no effect on other pituitary cell types.

Adult↗
PubMed1988

Automatic classification of two-dimensional gel electrophoresis pictures by heuristic clustering analysis: a step toward machine learning.

The interpretation of two-dimensional gel electrophoresis (2-DGE) profiles can be facilitated by artificial intelligence and machine learning programs. We have incorporated into our 2-DGE computer analysis system (termed MELANIE-Medical Electrophoresis Analysis Interactive Expert system) a program which automatically classifies 2-DGE patterns using heuristic clustering analysis. This program is a step toward machine learning. In this publication, we describe the classification method and the preliminary results obtained with liver biopsy electrophoretograms. Heuristic clustering is also compared to other classification techniques.

Algorithms↗
PubMed1988

Dexamethasone treatment increases neuropeptide Y levels in rat hypothalamic neurones.

Immunoreactive glucocorticoid receptors (GR) have previously been demonstrated in neuropeptide Y (NPY) neurones of the rat hypothalamus. To determine whether NPY synthesis is influenced by glucocorticoids, the effect of dexamethasone (DEX) on the levels of immunoreactive NPY in rat hypothalamic neurones was investigated in vivo and in vitro. Daily injections of DEX (0.1 mg/day) for 5 days increased the NPY content of the mediobasal hypothalamus in female rats by 117% (p less than 0.002). Primary cultures of hypothalamic neurones were also sensitive to the effect of glucocorticoids. Intracellular NPY levels were significantly increased (p less than 0.001) compared to control values by 151%, 222% and 268% when cultures were maintained in a defined serum free medium containing DEX 10(-9), 10(-8) and 10(-7) M respectively.

Animals↗
PubMed1988

Corticotropin releasing factor activity of CRF 41 in normal man is potentiated by angiotensin II and vasopressin but not by desmopressin.

Multiple hypothalamic factors seem to influence ACTH release. In vitro and/or in vivo animal models have shown that angiotensin II, vasopressin and some of its analogs are ACTH secretagogues capable of potentiating the corticotropin releasing activity of CRF41. Since these effects are controversial in man, we investigated in 3 groups of volunteers the corticotropin releasing activity of a 2h-infusion of angiotensin II (7 ng/kg/min), vasopressin (1 ng/kg/min) and desmopressin (1 ng/kg/min) given alone or in combination with a bolus injection of 100 micrograms CRF41 by measuring plasma concentrations of ACTH, cortisol, dehydroepiandrosterone and delta 4-androstenedione. Given alone angiotensin II and desmopressin had no significant effect in contrast to vasopressin which increased significantly the ACTH and steroid levels. Angiotensin II and vasopressin were both able to potentiate the corticotropin releasing activity of CRF41, whereas desmopressin was unable to produce such a potentiation. These results suggest that in man vasopressin and angiotensin II may well regulate the responsiveness of the pituitary-adrenal axis in various physiological or pathophysiological situations.

Adrenocorticotropic Hormone↗
PubMed1988

Human recombinant interleukin-1 beta and -alpha, but not recombinant tumor necrosis factor alpha stimulate ACTH release from rat anterior pituitary cells in vitro in a prostaglandin E2 and cAMP independent manner.

The pituitary-adrenal axis is known to be stimulated during the acute-phase response. As cytokines play a central role in mediating the constellation of host response occurring during the acute-phase response it was of interest to assess the ability of cytokines to stimulate ACTH secretion from normal pituitary cells in culture. We used human recombinant interleukin-1 beta and -alpha (hrIL1 beta, hrIL1 alpha) and human recombinant tumor necrosis factor alpha (hrTNF alpha) to analyze the ability of these cytokines to induce ACTH secretion from normal rat anterior pituitary cells in culture. We also investigated the possible roles of prostaglandin E2 (PGE2) and cAMP in the cellular transduction mechanism. After 3 days of incubation primary cultures of rat anterior pituitary cells were stimulated for 24 h with either hrIL1 beta, hrIL1 alpha or hrTNF alpha alone or with the addition of dexamethasone or indomethacin. The culture media were analyzed for ACTH, PGE2 and cAMP content. At doses ranging from 0.03 to 30 nM, hrIL1 beta stimulated the release of ACTH and PGE2 in a dose-dependent manner. In contrast, at doses ranging from 3 to 60 nM, hrTNF alpha was unable to stimulate ACTH secretion although it stimulated PGE2 synthesis. Time-course experiments demonstrated that hrIL1 beta (3 nM) stimulates ACTH production over a period of 8, 16 and 24 h, but not after a period of 4 h. In these experiments, hrIL1 beta failed to cause any change in the secretions of growth hormone and luteinizing hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗