Biomedical subjects

K Schmidt

Publications and source records attributed to K Schmidt.

At least 361 records · Page 20Linked to original sources

PubMed1991

Cellular mechanisms of action of therapeutic nitric oxide donors.

A survey of the available literature leads to the conclusion that the most probable mechanism by which nitrovasodilators act, is by nitric oxide (NO) formation. This by itself or by formation of a nitrosothiol (e.g. nitroscocysteine) activates guanylyl cyclase which increases the production of cyclic guanosine monophosphate (cGMP). Endothelium-derived relaxing factor (EDRF), which later turned out to be or to form NO, relaxes smooth muscle by stimulating cGMP formation. The effect of cGMP is mediated by a cGMP-dependent protein kinase and causes a reduction in the intracellular concentration of free Ca2+ ions in the smooth muscle cell. The precise mechanism of this effect is not completely clear but sequestration into sarcoplasmatic reticulum seems to play a major role. In order to identify the nature of the endogenous stimulator of guanylyl cyclase, i.e. to decide whether it is a nitrosothiol or the free radical NO, we compared the effects of NO, nitrosocysteine and nitrosoglutathione on vascular relaxation and increases in cGMP levels in isolated bovine circular strips and on guanylyl cyclase activity in vitro. Induction of tolerance and of cross-tolerance between various NO donors was also investigated. Nitrosodium and nitrosoglutathione augmented cGMP and relaxed vascular smooth muscle slightly more powerfully than NO. The three agents induced slight tolerance after repeated administration without affecting cGMP rises or desensitizing guanylyl cyclase. Pretreatment of coronary strips with nitrosoglutathione caused largely similar cross-tolerance as did NO against nitroglycerin, SIN-1 and sodium nitroprusside. The similarities to NO characterize nitrosocysteine as its most likely precursor, e.g. as EDRF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Importance of the recognition of a warning leak as a sign of a ruptured intracranial aneurysm.

In the Danish Aneurysm Study 1076 patients (pts.) were admitted with an aneurysmal subarachnoid hemorrhage in the 5-year period 1978-83. A warning leak (WL), defined as a sudden episode of headache, vomiting, nuchal pain, dizziness or drowsiness, was identified in 166 pts. (15.4%). In 99 of these the episode was evaluated by a physician but misdiagnosed. A 2-year follow-up examination of the 99 pts. showed that 30 pts. had a normal mental outcome and 43 pts. were dead. If these patients were correctly diagnosed after the WL, when they were in Hunt grade 1-2, the outcome-figures would probably have been significantly better. A theoretical transfer of the outcome-probabilities for pts. in Hunt grade 1-2 to the above mentioned 99 pts. would result in 66 pts. with a normal mental outcome and 25 dead pts. This shows the importance of recognition of a WL episode.

Adolescent↗

PubMed1991

Effect of bromocriptine withdrawal in acromegaly on body composition as assessed by bioelectrical impedance analysis.

To evaluate the effect of bromocriptine withdrawal after dopaminergic long-term treatment (15.0 +/- 6.8 mg/day, mean +/- SD) in 12 acromegalic patients on body composition, bioelectrical impedance was measured before and at the end of two weeks of drug withdrawal. During withdrawal basal hGH and IGF-I increased from 2.5 +/- 1.9 micrograms/l and 2.1 +/- 0.8 kU/l to 9.1 +/- 11.7 micrograms/l and 4.9 +/- 2.2 kU/l, respectively, and the hGH secretion deteriorated significantly both after oral glucose load and in the TRH test, indicating recurrence of active acromegaly. Reactance and resistance decreased by 5 +/- 4 and 23 +/- 19 omega, respectively (p less than 0.01), whereas body weight remained constant (+0.4 +/- 2.1 kg). Bioelectrical impedance analysis indicated evident shifts in body composition, i.e. a significant reduction of body fat (-2.0 +/- 1.7 kg) and a simultaneous increase in both lean body mass (+2.4 +/- 2.2 kg) and total body water (+1.8 +/- 1.6 l). The changes in body composition were related to a combined effect of unsuppressed hypersomatotropism and the lack of bromocriptine actions other than inhibition of hGH secretion (for example stimulation of the renin-angiotensin-aldosterone system by both the recurred hypersomatotropism and the absence of dopaminergic bromocriptine effects). We conclude that bioelectrical impedance analysis is a good additional tool to assess the pathophysiological effects of bromocriptine withdrawal in long-term treated acromegalic patients.

Acromegaly↗

PubMed1991

Determination of cytoplasmic calcium concentration in Dryopteris spores: a developmentally non-disruptive technique for loading of the calcium indicator fura-2.

Germination of Dryopteris spores is mediated by the physiologically active, far-red-absorbing form of phytochrome, Pfr, and external Ca2+ is necessary for the transduction of the light signal. Because knowledge about the cytoplasmic calcium ion concentration, [Ca2+]i, is of great importance for understanding the role of calcium during signal transduction, this value was measured using fura-2 in fern spores undergoing the normal developmental progression into germination. Fura-2 was loaded into the spores by electroporation, which does not disrupt the normal process of germination. The intensity of the fluorescence emission of the loaded fura-2 was analysed by a microspectrophotometric assay of single spores, and successful loading could be obtained by the application of ten electrical pulses (field strength 7.5 kV cm-1, half-life (time constant) 230 microseconds). Fura-2 was alternately excited by light of wavelengths 355 and 385 nm through an inverted fluorescence microscope, and the emitted fura-2 fluorescence was collected by a silicon-intensified video camera. The cytoplasmic calcium ion concentration was calculated from the ratio of the camera output obtained for both wavelengths and displayed by a pseudo-color technique. Spores responded to changes of the extracellular Ca2+ concentration, and this observation is considered as evidence that fura-2 is loaded into the cytoplasm. The substitution of a low external [Ca2+] (1 mM ethyleneglycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA)) by 1 mM CaCl2 caused a fast increase of [Ca2+]i from approx. 50 nM to above 500 nM. In contrast, the subsequent substitution of CaCl2 by EGTA decreased [Ca2+]i again below 100 nM within 0.5 h. Furthermore, the application of ionomycin could initiate a change in [Ca2+]i according to the Ca2+ gradient established between the extracellular medium and cytoplasm. In spores sown on a Ca(2+) -free medium, [Ca2+]i, analysed in a buffer containing EGTA, was found to be around 50 nM during the first days of cultivation, independent of the irradiation protocol. However, if spores were grown in darkness on a Ca(2+) -containing medium and analysed in EGTA, [Ca2+]i was significantly higher (> or = 500 nM). In red-light-irradiated spores, [Ca2+]i was found to decrease with increasing time after irradiation, and was determined to be less than 100 nM when analysis was done 44 h after germination was initiated by the light treatment.

Calcium↗

PubMed1991

Biological tolerance of Logiparin, a low molecular weight heparin used in patients undergoing total hip replacement.

Two hundred ten patients scheduled for THR were randomized into two groups. Group A (105 patients) received Logiparin (Novo-Nordisk, Denmark) 50 mg/kg body weight once daily, and group B (105 patients) received placebo once daily. Injections started 2 hr preoperatively and continued for 7 days. Blood samples were collected preoperatively before medication and 3 hr after last injection on the seventh postoperative day. Two hundred three patients completed the study: 103 in group A, 100 in group B. In group A there was a significantly higher increase in ASAT (p = 0.0006) and APH (p = 0.0137) compared with group B. Significantly more patients in group A showed an increase from normal preoperative values to pathological postoperative values in ASAT (p = 0.0012) and APH (p = 0.025) compared with group B. All changes were found to be reversible within 2 weeks of termination of drug treatment. Although no conclusion about the mechanism leading to the increase in ASAT and APH is possible from this data, there is very good suggestive evidence that the liver is influenced by this agent.

Double-Blind Method↗

PubMed1991

Left-ventricular performance, volumes, and catecholamine responses during anaesthesia induction--monitoring by combined radionuclide cardiography and right heart catheterization.

Sequential radionuclide imaging and continuous recording of arterial and right heart pressures were carried out during anaesthesia with midazolam 0.2 mg kg-1, pancuronium 0.15 mg kg-1 and fentanyl 10 micrograms kg-1 in eight patients with normal cardiopulmonary status scheduled for craniotomy. The aim was to examine how a stress-free anaesthetic induction tailored to protect against the hypertension and tachycardia provoked by laryngoscopy and intubation influenced left-ventricular performance, left-ventricular loading conditions and plasma catecholamine concentrations. During the 20-min study period no significant changes were observed in heart rate, left-ventricular ejection fraction, ratio of peak systolic pressure to left-ventricular end-systolic volume, pulmonary capillary wedge pressure, left-ventricular end-systolic volume, cardiac output, dopamine and noradrenaline concentrations. Except for a minor increase in mean arterial pressure after laryngoscopy and intubation, mean arterial pressure decreased 24%, left-ventricular end-diastolic volume decreased 15%, and left-ventricular stroke volume decreased 21%. Central venous pressure increased by 75% but there was no parallel increase in pulmonary wedge pressure, which in turn did not reflect the alterations in ventricular end-diastolic volume. Plasma adrenaline concentrations decreased significantly (66%). The chosen induction regimen preserved global left-ventricular pump function during laryngoscopy and intubation without any activation of the sympathetic nervous system. Central venous and pulmonary wedge pressures were unreliable in the assessment of ventricular preload during induction of general anaesthesia.

Adult↗

PubMed1991

Bradykinin-induced Ca(2+)-influx into cultured aortic endothelial cells is not regulated by inositol 1,4,5-trisphosphate or inositol 1,3,4,5-tetrakisphosphate.

Since inositol 1,4,5-trisphosphate (1,4,5-IP3) and inositol 1,3,4,5-tetrakisphosphate (1,3,4,5-IP4) have been described to modulate Ca(2+)-channels, we investigated the possible participation of 1,4,5-IP3 and/or 1,3,4,5-IP4 in the bradykinin-induced Ca(2+)-influx into cultured porcine aortic endothelial cells. In our experiments bradykinin induced a quick release of Ca2+ from intracellular stores and a longlasting Ca(2+)-influx, which remained constant for at least 15 minutes. In contrast to its effect on [Ca2+]i, bradykinin only transiently elevated 1,4,5-IP3 and 1,3,4,5-IP4 levels. Ten minutes after addition of bradykinin, both 1,4,5-IP3 and 1,3,4,5-IP4 levels returned to basal values, whereas Ca(2+)-influx was still unaltered. Furthermore, preincubation of endothelial cell with phorbol-12-myristate-13-acetate (PMA) abolished the stimulatory effect of bradykinin on the formation of 1,4,5-IP3 and 1,3,4,5-IP4, but did not affect the longlasting Ca(2+)-influx. These data provide evidence that in endothelial cells inositolphosphates are not involved in the regulation of bradykinin-induced longlasting Ca(2+)-influx.

Animals↗

PubMed1991

Cutaneous lesions of histoplasmosis with transepidermal elimination in a patient with acquired immunodeficiency syndrome.

Histoplasma capsulatum is a dimorphic pathogenic fungus that produces a variety of self-limiting disease syndromes in healthy persons, but commonly disseminates in immunocompromised hosts. Although histoplasmosis has been recently described in patients with acquired immunodeficiency syndrome, it is an uncommon finding, occurring in fewer than 0.5 percent of patients with acquired immunodeficiency syndrome. We are reporting a second case of disseminated histoplasmosis presenting as keratotic papules with transepidermal elimination of Histoplasma capsulatum. Our case demonstrates the importance of including histoplasmosis in the differential diagnosis of keratotic papules occurring in patients with acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Validation of physiologic predictors of successful telescopic spectacle use in low vision.

A group of 32 patients with low vision who were considered clinically appropriate candidates for visual rehabilitation with telescopic spectacles were prospectively studied before the first attempted use of these visual aids. Laboratory measurements were made of: (1) rotational head stability in pitch and yaw during quiet standing; (2) sensitivity of visual acuity with telescopic spectacles to imposed yaw head motion; and (3) ocular stabilization reflexes during passive, whole-body rotation in the horizontal plane. Predicted likelihood of successful use of telescopic spectacles was prospectively computed for each patient using the measurement of head stability in the pitch axis and the sensitivity of visual acuity with telescopic spectacles to head motion using a previously described statistical method. Patients were then given telescopic spectacles, and functional success was evaluated in the field at least 6 weeks later by independent masked observers. Although corrected visual acuities did not differ in the 24 patients in whom rehabilitation was successful or in the 8 patients in whom it was not, successful patients had statistically significantly less (P less than 0.05) angular head instability in pitch and yaw, as well as less impairment of visual acuity with telescopic spectacles during head motion. This finding was confirmed in a more clinically homogeneous subgroup of 16 patients who had low vision due to maculopathy. Gains of the 0.1 Hz horizontal vestibulo-ocular reflex (VOR) and visual-vestibulo-ocular reflex (VVOR) with 4X telescopic spectacles did not differ between patients in whom rehabilitation was successful and those in whom it was not.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

Serum osteocalcin levels in rheumatoid arthritis: a marker for accelerated bone turnover in late onset rheumatoid arthritis.

Levels of serum osteocalcin (OC) are increased in diseases with high bone turnover. We determined OC levels in (1) 15 patients with definite rheumatoid arthritis (RA) in early stages according to Steinbrocker's functional class FC I-II, (2) 40 patients at advanced stages (FC III-IV) and (3) 17 patients with late RA (onset at age of 65 or more). Sixty-two healthy volunteers, divided into 3 subgroups corresponding to the patients, and 19 patients with primary fibromyalgia syndrome (FMS) served as controls. All patients were included in a short term as well as a longitudinal study over one year. Mean OC levels were significantly elevated in patients with late onset RA compared with healthy controls (p = 0.037), while the OC values in early RA FC I-II and advanced RA FC III-IV did not differ significantly from the corresponding control group and the patients with FMS. The late RA group showed a positive correlation between OC and the erythrocyte sedimentation rate (ESR) (r = 0.641, p = 0.007) with a significant decrease of OC (p less than 0.01) as well as ESR (p = 0.047) over one year. We conclude increased OC levels correlate with disease activity in older patients with active RA, suggesting impaired bone turnover. This finding supports the picture of heterogeneity in RA with more late onset patients displaying "high bone turnover."

Adult↗

PubMed1991

[Vitamins, minerals and trace elements in elderly people].

In western industrial countries the proportion of elderly people is 15 to 20% of the total population with an increasing tendency. This fact is in contrast to a remarkable gap of knowledge on the process of ageing per se, nutritional influences, and particularly interrelationships with specific disease states such as multimorbidity of elderly people. It is obvious that the elderly people do require health care and social support to a much greater extent than other groups of a society. Also, multidisciplinary approaches are required in order to successfully perform research projects in this complex area. Finally, the economical significance of this particular problem of preventive medicine is tremendous. Micronutrients such as vitamins, minerals, and trace elements do play an important role in maintaining the metabolic homeostasis in elderly people as well as in the prevention of many age-associated diseases.

Aged↗

PubMed1990

[Long-term treatment of acromegaly with the somatostatin analog octreotide (Sandostatin). On the predictive significance of acute tests].

Twelve acromegalic patients were treated (mean +/- SD) 26 +/- 15 months with daily doses of 440 +/- 330 micrograms of the somatostatin analogue octreotide acetate (SMS 201-995, Sandostatin). The levels of somatomedin-C (Sm-C) decreased by 63% from 8.1 +/- 7.7 U/ml to 3.0 +/- 1.3 U/ml. Before starting therapy a long oral glucose tolerance test (oGTT) and a TRH test were performed both without and after s.c. injection of 100 micrograms octreotide. Under long-term treatment with octreotide four of twelve patients reached normal Sm-C-values. The GH levels of all of these patients were continuously suppressed to less than 2 ng/dl in an oGTT after a test dose of 100 micrograms octreotide s.c. till the end of the test (5 1/2 hours after octreotide injection). The other eight patients had a relief of acromegalic symptoms and five had a decrease of their Sm-C-levels, but none of them reached normal Sm-C-values. None of these patients had a continuous suppression of GH after a test dose of octreotide in an oGTT. Hyperprolactinemia (n = 4) was observed only in those patients with an insufficient response to octreotide. The GH-response to TRH showed neither without nor after injection of octreotide a correlation with the results of long-term treatment. Thus it is concluded that GH-suppression in a long oGTT after administration of a test dose of 100 micrograms octreotide acetate s.c. allows to identify those acromegalic patients who will benefit from long-term treatment with the somatostatin analogue octreotide acetate.

Acromegaly↗

PubMed1990

Activation of soluble guanylate cyclase by nitrovasodilators is inhibited by oxidized low-density lipoprotein.

In the presence of oxidized low-density lipoprotein the stimulatory effects of nitric oxide, sodium nitroprusside and S-nitrosoglutathione on soluble guanylate cyclase partially purified from bovine platelets were diminished in a concentration-dependent manner with IC50 values around 100 micrograms total cholesterol/ml. This inhibitory effect was potentiated about 10-fold when the enzyme was pre-incubated with the lipoprotein for 10 minutes at 37 degrees C which indicates a direct interaction of the lipoprotein with the guanylate cyclase. As oxidized low-density lipoprotein is present in the wall of atherosclerotic arteries, we suggest that the impaired response of atherosclerotic blood vessels to vasodilators may be due to a diminished activation of smooth muscle guanylate cyclase.

Animals↗

PubMed1990

Pyridoxine-unresponsive homocystinuria with an unusual clinical course.

Progressive premature atherosclerosis and associated thromboembolic complications are the main causes of morbidity and mortality in patients with homocystinuria. However, thrombosis is rarely the predominant or presenting manifestation leading to the diagnosis of homocystinuria. We report on an otherwise asymptomatic teenage boy of normal intelligence who had a superior sagittal sinus thrombosis documented by CT and MRI scans. He presented with pneumothoraces, papilledema, and transient right hemiparesis. He subsequently developed empyema and necrotizing pneumonia as well as deep venous thromboses. The diagnosis of pyridoxine-unresponsive homocystinuria was made on the basis of clinical chemistry analyses, enzyme assay, and clinical trial. He has remained symptom-free under treatment with betaine and methionine restriction. We suggest that there exists a subset of patients with pyridoxine-unresponsive homocystinuria who are at risk for thromboembolism, but who may remain undiagnosed because of an otherwise mild clinical course.

Adolescent↗

PubMed1990

Lipid transfer proteins.

Translocations of various lipid species between membranes have been extensively studied. The transport of water-insoluble lipids is thought to require the participation of lipid transfer proteins (LTP). Several LTP, differing in their physiochemical properties and substrate specificities, have been purified to homogeneity from blood plasma, eucaryotic and procaryotic cells. Depending on their site of activity, they can be classified as extracellular and intracellular LTP. Extracellular LTP are found in the blood plasma and intracellular LTP, which were originally characterized as phospholipid exchange proteins, are ubiquitous in nature. Despite the enormous knowledge about their physicochemical properties and their function in vitro their physiological role has not been clearly demonstrated. However, their ubiquitous occurrence indicates an important role in cellular events. This review gives an overview of this interesting category of proteins, which are able to catalyze inter-membrane transfer and exchange of lipids.

Animals↗

PubMed1990

Homosexual and bisexual men's coping with the AIDS epidemic: qualitative interviews with 10 non-HIV-tested homosexual and bisexual men.

This paper describes how the threat of HIV infection is appraised and coped with by homosexual and bisexual men. Very little is known about men who do not want to be HIV tested, thus non-HIV-tested homosexual and bisexual men have been interviewed in depth about themes concerning their lives during the AIDS epidemic. Men with sexual risk behaviour appeared to be very reluctant to participate, and therefore six men with safe sexual behaviour and four men with unsafe sexual behaviour were interviewed. The results showed that all the men were well informed about AIDS and preventive measures. Reasons for not wanting a test were fear of psychological distress caused by a possible positive test and the fact that no treatment is available. The men who had adopted safe sex appraised their sex lives to have suffered a minor loss but found that sexuality played a subordinate role compared to trust and friendship. The men with risk behaviour considered sexuality to play an important role in their lives. They found condoms a barrier to intimacy and used defensive strategies to manage stress. Most of them were able to exchange social support with their network but had difficulties in setting their own limits. All four men had experienced undertreated traumatic events in their past. The results indicate that knowledge of AIDS and satisfactory social support do not necessarily result in safe sexual behaviour. The role of undertreated traumatic events forming barriers against adopting safe sexual practices should be further studied. Proposals are put forward for future health education programmes.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Effect of sodium fluoride on cytosolic free Ca2(+)-concentrations and cGMP-levels in endothelial cells.

Sodium fluoride was used to investigate a possible involvement of G-proteins in the regulation of endothelial calcium channels. Incubation of cultured porcine aortic endothelial cells with sodium fluoride produced a dose-dependent increase in intracellular free calcium (EC50 approximately 5 mM). The effect strictly depended on the presence of extracellular CaCl2, indicating an enhanced influx of extracellular Ca2+ rather than a release of Ca2+ from intracellular stores. The Al3+ chelator deferoxamine abolished the stimulatory effect of sodium fluoride but did not interfere with the stimulatory effect of bradykinin. These data confirm the current hypothesis that the complex AlF-4 and not the fluoride anion activates G-proteins and exclude a direct inhibitory effect of deferoxamine on Ca2(+)-uptake. In contrast to isoproterenol and 5'-N-ethylcarboxamido-adenosine (NECA), which elevated endothelial cAMP-levels without affecting intracellular Ca2(+)-concentrations, sodium fluoride was not able to increase endothelial cAMP. This indicates that the effect of sodium fluoride on endothelial Ca2(+)-levels is not due to stimulation of a Gs-protein. Similar to its effect on cytoplasmic Ca2+, sodium fluoride also increased endothelial cGMP-levels which has recently been suggested to serve as biochemical marker for the formation of endothelium derived relaxing factor (EDRF). Thus, similar to the activation of receptor operated calcium channels, direct stimulation of a G-protein by sodium fluoride results in an increase of cytoplasmic Ca2+ and the formation of EDRF.

Animals↗

PubMed1990

In vivo inhibition of tumor growth of B16 melanoma by recombinant interleukin 1 beta. II. Mechanism of inhibition: the role of polymorphonuclear leukocytes.

Recombinant human interleukin 1 beta (IL 1 beta) inhibits growth of B16 melanoma in syngeneic C57BL/6 mice in a dose-dependent manner when given intratumorally, intradermally, or intramuscularly over a period of 5 to 7 days. Inhibition of tumor growth was rapid and measurable within 3 days after the initial injection and occurred regardless of the route of injection. However, only intratumoral (ITU) injections of IL 1 beta resulted in greater than 90% inhibition in tumor growth. This enhanced inhibition of tumor growth was not dependent on T or NK cells since inhibition of tumor growth occurred in nude and Beige mice. Also, a profound lymphopenia occurred in mice receiving IL 1 beta. Inhibition of tumor growth did correlate with an increase in the number of polymorphonuclear leukocytes (PMN's) in the circulation. However, only ITU injections of IL 1 beta increased the number of PMN's within the tumors. IM injections of IL 1 beta, while increasing the number of PMN's in the circulation, did not increase the influx of PMN's into the tumors. Furthermore, the transfer of PMN's directly into B16 tumors caused a 49% reduction in tumor growth without the presence of IL 1 beta. These results suggest that in vivo, PMN's may effectively control the growth of tumors and that IL 1 beta may increase this effectiveness by increasing the number of PMN's in the circulation and by locally stimulating the production of chemotactic factors for PMN's within the tumor.

Animals↗