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Biomedical subjects

M Stoll

Publications and source records attributed to M Stoll.

At least 109 records · Page 6Linked to original sources

Sulfated blood group Lewis(a). A superior oligosaccharide ligand for human E-selectin.

In earlier studies of oligosaccharide probes (neoglycolipids) generated from an ovarian cystadenoma glycoprotein, one of the components that strongly supported binding of the endothelial adhesion molecule, E-selectin, was identified as an equimolar mixture of tetrasaccharides of blood group Le(a) and Le(x) type sulfated at position 3 of the outer galactose (C.-T. Yuen, A. M. Lawson, W. Chai, M. Larkin, M. S. Stoll, A. C. Stuart, F. X. Sullivan, T. J. Ahern, and T. Feizi (1992) Biochemistry 31, 9126-9131). In the present studies, the individual sulfated Le(a) and sulfated Le(x) oligosaccharides synthesized chemically have been investigated, first, for their ability to support E-selectin binding when converted into neoglycolipids, and second, for their ability to inhibit E-selectin binding to immobilized lipid-linked sialyl-Le(a), sialyl-Le(x), or sulfated Le(a) pentasaccharides; their activities have been compared with those of the sialyl-Le(a) and sialyl-Le(x) analogues. From these studies, the sulfated Le(a) tetra- and pentasaccharides emerge as the most potent E-selectin ligands so far. In particular, the inhibitory activity of the sulfated Le(a) pentasaccharide is substantially greater than that of the sialyl-Le(x) trisaccharide, which is currently the most widely used inhibitor of E-selectin binding: 45-, 35-, or 15-fold greater depending on whether adhesion is to sialyl-Le(a), sulfated Le(a), or sialyl-Le(x) pentasaccharides, respectively. These findings have an important bearing on design of new generations of inhibitors of E-selectin binding as antiinflammatory compounds.

Animals↗

[The value of various transcranial color doppler tests for determining cerebrovascular reserve capacity].

One of the techniques for the assessment of the cerebrovascular reserve capacity is the so-called "breath-holding" test. In order to minimise haemodynamic changes following deep inspiration the patients should hold their breath at the end of a normal inspiration. We studied three different ways (breath holding following normal inspiration [NI], deep inspiration [DI], hyperventilation [HV]), of performing this test in 20 healthy volunteers. The acetazolamide test was taken as a reference. The mean flow velocity (FVmean) in the middle cerebral artery was recorded continuously using a TCD monitoring system. Blood pressure, cardiac output and heart rate were measured simultaneously. Breath holding after deep inspiration resulted in longer apnoea (DI: 68.1 +/- 24.1 s; NI: 44.8 +/- 18.4 s; p < 0.01), produced the highest increase of FVmean (DI: +72.2 +/- 29.8%; NI: +69.2 +/- 29.0%) and was the least inconvenient to the patients. Following HV apnoea was longest (93.0 +/- 33.5 s; p < 0.01), but resulted in the lowest increase of FVmean were not significant. A significantly lower increase of FVmean (44.2 +/- 13.4%, p < 0.01 resp.) could be observed after intravenous injection of 1 g acetazolamide. There were no significant haemodynamic changes in any case. Thus, this bedside test does not appear to be influenced by variations in breath holding.

Acetazolamide↗

Simultaneous measurement of cardiac output by thermodilution, thoracic electrical bioimpedance and Doppler ultrasound.

To evaluate the accuracy of two non-invasive techniques for cardiac output (CO) measurement, we have measured CO simultaneously by thoracic electrical bioimpedance (TEB), pulsed Doppler ultrasound (DU) and standard thermodilution methods (TD) under different clinical conditions. Measurements were made in 10 patients: (I) during steady state anaesthesia with controlled IPPV ventilation (n = 131), spread over the entire ventilatory cycle; (II) during apnoea (n = 56); (III) during spontaneous breathing (n = 152) in the intensive care unit. Mean (SD) cardiac output values were: (I) COTD 3.5 (1.0) litre min-1, COTEB 3.4 (0.7) litre min-1, CODU 2.8 (0.7) litre min-1; (II) COTD 3.6 (0.6) litre min-1, COTEB 3.5 (0.4) litre min-1, CODU 2.9 (0.7) litre min-1; (III) COTD 7.7 (1.5) litre min-1, COTEB 7.6 (1.9) litre min-1, CODU 5.2 (1.4) litre min-1. The mean percentage deviation of TEB from TD ranged from -2.2% to 1.4% and that of DU from TD was from -16% to -32%. There were no statistically significant differences between TD and TEB, but TD and DU differed significantly during IPPV, apnoea and spontaneous ventilation (P < 0.0001).

Adult↗

Big endothelin in spontaneous intracerebral hemorrhage.

Plasma big endothelin (BE) levels were studied in 17 patients during the first 2 weeks following spontaneous intracerebral hemorrhage (ICH). Three patients had experienced an infratentorial hemorrhage of the pons and cerebellum. The group of 14 patients with supratentorial hemorrhage presented with 8 hematomas of the putamen, 4 of the capsula interna and 2 in the thalamus. Significant elevations of BE during the first 2 weeks after the initial ICH, significant differences between the different localisations and between patients with different prognoses were not apparent (mean BE level: 2.95 +/- 1.39, control group: 2.68 +/- 1.29 fmol/ml). These results support the theory that endothelins do not play a significant pathophysiological role in acute severe ICH.

Adult↗

The renin-angiotensin system in the heart and vascular wall: new therapeutic aspects.

Traditionally, the renin-angiotensin system (RAS) has been viewed as an endocrine system. Recently, independent tissue RASs have been postulated that are believed to act in a paracrine/autocrine fashion. Elements of the RAS have been shown to exist in many peripheral tissues. Angiotensin-converting enzyme (ACE), a key element of the RAS, is found mainly in the vascular endothelium and therefore represents the main target site for inhibition of the local and circulating RASs. In the heart, angiotensin II exerts a direct positive inotropic and chronotropic effect. More recently, it was also found that angiotensin II may act as a growth factor in several cell types. Angiotensin II is also thought to be partially responsible for structural remodeling in cardiac hypertrophy. The role of ACE inhibitors has been established in the treatment of hypertension and congestive heart failure. Recent multicenter trials revealed a beneficial role of ACE inhibitors in reduction of mortality rates in patients with congestive heart failure and a low ejection fraction. Mechanisms that include reduction of myocardial oxygen demand, improvement of coronary blood flow, induction of capillary proliferation, reduction of blood pressure and ventricular wall tension without reflex tachycardia, and impairment of myocardial contractility are the basis for the beneficial effects of ACE inhibitors. In addition to a reduction of angiotensin II generation, these effects appear to be largely brought about by the inhibition of endogenous kinin degradation. Recent studies suggest that a deletion polymorphism in the gene encoding ACE is a risk factor in myocardial infarction (MI).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

[Mycobacterium genavense infection in AIDS].

Fever, loss of weight, anaemia, hepatosplenomegaly and lymphadenopathy developed in two HIV-infected patients. At first malignant lymphoma with septicaemia was thought to be the cause. In both patients Salmonella enteritidis was isolated by blood culture and found to be sensitive against the antibiotics that were given (5 g azlocillin and 2 g cefotaxime, three times daily each; additionally in case 2, metronidazole, 500 mg three times daily). Because bone-marrow biopsy demonstrated acid-fast rods, antimycobacterial treatment was started (isoniazid 300 mg/d, rifampicin 600 mg/d, ethambutol 1,200 mg/d and pyrazinamide 2 g/d). Despite this the patients died of septic shock. Histological examination revealed massive amounts of acid-fast rods in spleen, liver, gut and bone marrow. Polymerase chain reaction and sequencing identified the structure as that of the recently discovered M. genavense.

AIDS-Related Opportunistic Infections↗

Effect of recombinant human erythropoietin after allogenic bone marrow transplantation.

The hematologic effects of recombinant human erythropoietin after allogeneic bone marrow transplantation (BMT) were studied. Nineteen patients received 150 U/kg/day of C127 mouse-cell-derived recombinant human erythropoietin (rHu EPO) as a daily continuous intravenous infusion until hematocrit exceeded 35%. These data were compared with a treatment-matched historical control group of 43 patients. RHu EPO-treated patients recovered erythropoiesis more rapidly and became independent from erythrocyte transfusions after a median of 17 days, which was 7 days earlier than the control patients.

Adolescent↗

Renin activation correlates with blood amount and distribution in subarachnoid haemorrhage.

Blood extent and localization visible in CCT predicts complications and prognosis in patients suffering from subarachnoid haemorrhage (SAH). Plasma renin activity (PRA) elevation is one of the hormonal parameters of autonomic disorders after SAH and its prognostic relevance could be confirmed by this study, too. But the correlation of PRA with blood amount and distribution was the main target of this study. Large amounts of blood are connected with higher PRA-levels and more PRA-rises. Even a linear correlation between the amount of blood defined by a CCT-score and PRA in ng ml h-2 could be established. A significant correlation was found between intraventricular, suprasellar blood, ventricular enlargement of the third/lateral ventricles and PRA-elevations. Disorders of hypothalamic and/or medullary centres of sympathetic control are thought to be the underlying cause and to depend on blood extent and distribution.

Adult↗

Flunixin meglumine blocks frusemide-induced bronchodilation in horses with chronic obstructive pulmonary disease.

Six horses that developed acute airway obstruction (heaves) when housed in a barn and fed poor-quality hay were studied. Airway obstruction was verified by a maximal change in pleural pressure during tidal breathing (delta Pplmax) of at least 15 cmH2O. Frusemide (1.0 mg/kg bwt) or an equivalent volume of vehicle was then administered intravenously (iv) and lung function was measured 15, 30, 60, 120, 180, 240 and 300 mins after drug administration. The effect of frusemide on lung function was also studied after treatment of horses with the cyclooxygenase inhibitor flunixin meglumine (1.1 mg/kg every 8 h for 2 days before the experiment). Frusemide significantly reduced the delta Pplmax beginning 15 mins after drug administration. This effect persisted for 5 h. The reduction in delta Pplmax was due partly to an increase in dynamic compliance and partly to a decrease in pulmonary resistance. Tidal volume and respiratory frequency were unaffected by frusemide. Vehicle had no effect on lung function. Flunixin meglumine abolished the effect of frusemide on airway calibre but did not prevent diuresis. These results indicate that the effect of frusemide on airways of horses with heaves persists for at least 5 h, is mediated through prostanoids, and is not a result of diuresis.

Analysis of Variance↗

CD16- CD56+ natural killer cells after bone marrow transplantation.

Natural killer (NK) cells are phenotypically defined as lymphocytes expressing the antigens CD56 and mostly CD16 (Fc gamma RIII), but lacking CD3. A small CD3- CD16- CD56+ NK cell subset has been described in normal individuals representing less than 2% of peripheral blood lymphocytes. We analyzed here 70 patients for their reconstitution of the immune system during follow-up after autologous or allogeneic bone marrow transplantation. In 35% of these patients, two different NK cell subsets, namely CD56+dim and CD56+bright cells, were observed. The mean duration of these two subsets after transplant was 4 months. Sixty-five percent of the patients exhibited an increased number of NK cells, but only the typical CD16+ CD56+dim population. The CD56+bright subpopulation represented a particular CD3- CD16- NK subset, with posttransplant frequencies up to 70% of all NK cells and 40% of peripheral blood lymphocytes, respectively. In contrast to normal CD56+dim NK cells, CD56+bright cells coexpressed the activation antigens p75 beta-chain of interleukin-2 receptor (IL-2R), CD2R, and CD26, but were negative for CD16. NK and antibody-dependent cellular cytotoxicity activity of CD56+bright cells was low compared with CD56+dim NK cells. But using IL-2 and interferon gamma, their cytotoxicity could be enhanced even more than in CD56+dim lymphocytes. These different subsets may reflect distinct activation or differentiation steps of NK cells during reconstitution of the immune system. Their differential response to IL-2 may be of functional importance for posttransplant cytokine therapy.

Adult↗

Ultrasound examination of the stomach contents of parturients.

A noninvasive method to determine the actual stomach contents of parturients may help to identify factors responsible for delayed gastric emptying as well as define the risk of aspiration of gastric contents in individual patients. Therefore, we tested the ability of ultrasound imaging to identify noninvasively the stomach contents of laboring and nonlaboring pregnant volunteers. A preliminary study demonstrated that the stomach contents could be identified by ultrasound in 20 healthy volunteers and in 34 parturients, not yet in active labor, scanned after consuming liquids or solid food. Next, 39 parturients in active labor were scanned at varying postprandial times. Sixteen parturients in active labor who had not eaten for 8-24 h still had food detected in the stomach. In fact, nearly two-thirds of the patients in active labor who were scanned had solid food present in the stomach independent of the interval between last oral intake and the ultrasound scan. The present study demonstrates that high-resolution ultrasonography is capable of noninvasively identifying the stomach contents of parturients. These results confirm the clinical impression that emptying of the stomach is delayed for many hours after the onset of labor.

Adult↗

[A personal computer-based system for online monitoring of neurologic intensive care patients].

In the management of neurological intensive care patients with an intracranial space-consuming process the measurement and recording of intracranial pressure together with arterial blood pressure is of special interest. These parameters can be used to monitor the treatment of brain edema and hypertension. Intracranial pressure measurement is also important in the diagnosis of the various subtypes of hydrocephalus. Not only the absolute figures, but also the recognition of specific pressure-patterns is of particular clinical and scientific interest. This new, easily installed and inexpensive system comprises a PC and a conventional monitor, which are connected by an AD-conversion card. Our software, specially developed for this system demonstrates, stores and prints the online-course and the trend of the measurements. In addition it is also possible to view the online-course of conspicuous parts of the trend curve retrospectively and to use these values for statistical analyses. Object-orientated software development techniques were used for flexible graphic output on the screen, printer or to a file. Though developed for this specific purpose, this system is also suitable for recording continuous, longer-term measurements in general.

Cerebral Hemorrhage↗

Cardiac and vascular effects of chronic angiotensin converting enzyme inhibition at subantihypertensive doses.

AIM: We performed two sets of experiments in order to prevent or to regress cardiac and vascular hypertrophy, using antihypertensive and subantihypertensive doses of the angiotensin converting enzyme inhibitor zabicipril. METHODS AND RESULTS: Spontaneously hypertensive rats (SHR) begin to develop hypertension at less than 4 weeks of age and reach stable hypertension levels after 12-14 weeks. The blood pressure increase is accompanied by the development of cardiac and vascular hypertrophy. Treatment of SHR in utero and up to the age of 20 weeks with an antihypertensive dose of zabicipril (1 mg/kg per day) not only prevented the development of high blood pressure but also the development of cardiac and vascular hypertrophy. This effect was demonstrated by a significant decrease in left ventricular weight and the number of smooth muscle cell layers in the vascular media, media thickness and the media:lumen ratio in mesenteric arteries. In contrast, antihypertensive treatment with the Ca2+ antagonist verapamil (100 mg/kg per day) and the subantihypertensive dose of zabicipril (0.01 mg/kg per day) did not affect the development of cardiac and vascular hypertrophy. We found a significant increase in the length and surface density of myocardial capillaries after treatment with zabicipril at 1 mg/kg per day, indicating that the capillary density had improved and therefore that the oxygen supply of the heart was improved. Similar findings were observed with the low dose of zabicipril in SHR, although these rats had high blood pressure and cardiac and vascular hypertrophy. CONCLUSIONS: Treatment of adult SHR for 16 weeks with zabicipril at 1 mg/kg per day completely normalized their blood pressure levels. This effect was accompanied by a regression of left ventricular but not of vascular hypertrophy. Treatment with an antihypertensive dose of verapamil or with a subantihypertensive dose of zabicipril had no effect on cardiac and vascular hypertrophy.

Angiotensin-Converting Enzyme Inhibitors↗

Survival of feline mycoplasmas in urine.

The effects of length of incubation and urine osmolality on the survival of feline mycoplasmas and ureaplasmas and representative gram-positive and gram-negative bacteria in synthetic urine which approximated the osmolality of normal cat urine were investigated. Both Escherichia coli and Staphylococcus aureus withstood the effects of increasing osmotic pressure. In the most concentrated urine, significant decreases (P less than 0.001) in CFU were observed for E. coli at exposure times of 30 min and longer. S. aureus was not affected by longer exposure or increased osmotic strength. Both Mycoplasma felis and Mycoplasma gateae were affected adversely by longer exposure times and high osmotic strength (P less than 0.001). A Ureaplasma sp. was not adversely affected except at very high (greater than or equal to 2,980 mosM) osmotic strengths or after prolonged incubation (120 min) at relatively high (1,976 mosM) osmotic strengths (P less than 0.001). The failure of both M. felis and M. gateae to survive under osmotic conditions present in normal feline urine suggests that it is unlikely that these mycoplasmas are involved in urinary disorders in cats.

Animals↗

Allogeneic bone marrow transplantation for Langerhans' cell histiocytosis.

A group of proliferative diseases of the epidermal Langerhans' cells are commonly referred to as Langerhans' cell histiocytosis (LCH). A small number of the patients with this disease face an unfavorable disease course despite chemotherapy and radiation therapy. In LCH patients with a poor prognosis, allogeneic bone marrow transplantation (BMT) could be the appropriate treatment with proven antiproliferative effects and may be able to repopulate the recipient with stem cell-derived Langerhans' cells from the donor or correct the presumed underlying immunodeficiency. An LCH was diagnosed in a 15-year-old boy with multiple osteolytic lesions, anemia, and diabetes insipidus centralis. Repeated flare-ups of the disease had necessitated several courses of conventional chemotherapy including cyclophosphamide (CY), prednisolone (P), 6-mercaptopurine (6-MP), vincristine (VCR), and additional local irradiation without stable remission. Three years after first being diagnosed with LCH the patient underwent high-dose chemotherapy-radiation therapy followed by allogeneic BMT from his human lymphocyte antigen (HLA)-identical brother. Currently, he is alive and well and has been disease-free for more than 41 months after BMT.

Adolescent↗

Identification of a novel oligosaccharide backbone structure with a galactose residue monosubstituted at C-6 in human foetal gastrointestinal mucins.

An oligosaccharide purified from a major penta- to hexa-saccharide fraction of human meconium glycoproteins has been shown by m.s. and n.m.r. analysis to have a novel backbone structure containing an internal galactose residue monosubstituted at C-6 by N-acetylglucosamine: (Formula: see text). This oligosaccharide may represent a biosynthetic product of a previously unrecognized N-acetylglucosaminyltransferase catalysing formation of a linear GlcNAc beta 1-6Gal sequence.

Carbohydrate Conformation↗

Recombinant human granulocyte-macrophage colony stimulating factor (rh GM-CSF) after bone marrow transplantation.

Bone marrow transplantation improves the chances of survival in a variety of hematological malignancies. However, infectious complications during the post-transplant phase contribute significantly to morbidity and mortality. To reduce the duration of granulocytopenia, which is approximately 20 days after BMT, in this study patients with ALL, relapsed or high-grade NHL, relapsed or refractory HD, or Neuroblastoma stage III/IV, were given rh GM-CSF to assess the effects on hematological and immunological reconstitution after conditioning therapy and BMT. The results of 9 patients are presented. After autologous BMT and subsequent rh GM-CSF therapy, a peripheral blood neutrophil count of 500/microliters was reached within 8-12 days, i.e., between 7 and 10 days earlier than would have been expected without rh GM-CSF. Furthermore, it appeared that rh GM-CSF was useful in case of insufficient bone marrow regeneration post autologous transplant. The influence of rh GM-CSF after allogeneic BMT is not yet clear. Further studies will be necessary to evaluate the potential of this promising new drug after BMT.

Adult↗