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Biomedical subjects

L H Schmidt

Publications and source records attributed to L H Schmidt.

At least 19 recordsLinked to original sources

[Are our blood donors in danger of iron deficiency?].

In blood donors the question arises for eventual endangering by iron deficiency. The results of this work show that ferritin determinations for blood donors will indicate a latent, in some cases a manifest iron deficiency. The examination of testing components such as PVC, MCH, Fe i. S., transferrin and transferrin saturation produced no special advantages concerning sensitivity and specificity, in terms of ferritin determination. It is indispensable, however, to know the ferritin value because the control of the Hb value prior to blood donation will usually characterize the blood donor's situation in a sufficient manner. For control purposes it is possible to use capillary or venous blood. It is only in general, but particularly in special clinical situations that you have to be aware of the blood donor's condition concerning his/her Fe-metabolism.

Blood Donors↗

[Iron resorption and the effects of iron supplementation in blood donors].

Topical values for some haematological factors such as Hb and Ery as well as transferrin and ferritin were determined in 7 female blood donors and 8 male blood donors during the years of their work as blood donors. Subsequently, an iron resorption test was carried out which unexpectedly resulted in low rates of resorption ranging from 5.6% in men to 3.7% in women. After supplementing with vitaferro for 3 months the ferritin values which initially lay around the lower limiting value of 20 or 10 mg/l in men or women had doubled.

Blood Donors↗

[Expectations between the clinic and the clinical laboratory].

A considerable part of the paraclinical diagnostics and therapy control takes place in the clinical laboratory. The readiness for achievements of the clinical laboratory also depends on the responsible acquaintance with the demands of the laboratory and the observance of certain rules. The increasing number of possible test components and their peculiarities render possible their appropriate interpretation, also taking into consideration possible factors which have influence on the representance. A reasonable cooperation between laboratory and clinic is suitable to optimize and to realize the mutual expectations.

Clinical Laboratory Techniques↗

Fibrin monomer complexes (SFMC) after substitution of antithrombin III (AT III) in consumption coagulopathy.

The report refers to substitution therapy of 33 patients who suffered consumption coagulopathy. Various blood coagulation and fibrinolytic variables were measured. After successful AT III donation to patients suffering DIC, soluble fibrin monomer complexes (SFMC) disappeared within 0.5-12 hours. If AT III decreases SFMC proves positive again. In addition to analysis of AT III we recommend to analyse SFMC to detect thrombin induced consumption reaction (DIC). Furthermore we found the fibrin split product D-dimer was a particularly sensitive indicator of DIC in case of hyperfibrinolysis (D-dimer was analysed in six patients). The reactions of fibronectin and SFMC proved inversely proportional.

Adolescent↗

Attenuation of the virulence of the M strain of Plasmodium cynomolgi during prolonged multiplication in splenectomized rhesus monkeys.

The primary data in this report showed that prolonged multiplication of the M strain of Plasmodium cynomolgi in splenectomized rhesus monkeys led frequently to emergence of parasites whose virulence for monkeys with intact spleens was markedly attenuated while that for splenectomized monkeys was unimpaired. Expressions of attenuation regularly included reductions in the height of the peak parasitemia and in some instances failure to induce infection with inocula 1,000-fold those infective for splenectomized monkeys. Attenuation of virulence, once established, was maintained through as many as 17 serial passages in intact monkeys and more than 100 such transfers in splenectomized monkeys. Not only asexual blood stages, but also sexual stages (gametocytes) carried the attenuated characteristic, as indicated by its ready passage through mosquitoes. Studies in monkeys with sporozoite-induced infections showed that the persisting exoerythrocytic stages did not participate in the attenuation phenomenon; for when erythrocytic parasites of reduced virulence were cleared from the blood by either immune processes or chemotherapy, they were replaced upon relapse with parasites of unimpaired virulence. A major effort to determine whether splenectomized monkeys carried plasma or erythrocyte factors responsible for displays of attenuated virulence was nonproductive. An intact spleen was the essential element in these displays, for they disappeared immediately upon removal of this organ. The attenuation phenomenon probably reflects selection of spontaneously occurring mutants with limited capacity to escape normal splenic clearance mechanisms and unimpaired or even enhanced capacity to multiply in splenectomized monkeys.

Animals↗

Compatibility of relapse patterns of Plasmodium cynomolgi infections in rhesus monkeys with continuous cyclical development and hypnozoite concepts of relapse.

This report encompasses the results of two studies on the relapse patterns of infections with the B strain of Plasmodium cynomolgi treated repetitively with chloroquine. One study of sizeable dimensions dealt primarily with relapses that occurred within 120 days of onset of patency in infections induced with inocula of 10(5) to 7 X 10(6) sporozoites. The second study, of more limited dimensions, dealt with relapses that occurred over a 689-day period after inoculation with 5 X 10(0) to 5 X 10(6) sporozoites. Both studies showed that with few exceptions relapses occurred at relatively regularly spaced intervals. The second study showed that frequency of relapse was related directly to the size of the sporozoite inoculum and inversely to the age of the infection; also that an inoculum larger than the minimum infective dose was required for relapse. Attempted correlation of these observations with the new and generally accepted hypnozoite concept of relapse uncovered two areas of serious incompatibility and numerous defects in the experimental base of this conceptualization. With limited provisos, the relapse patterns of infections with P. cynomolgi are fully compatible with the older cyclical development concept. The results of this study argue for caution in discarding this concept and for continuation of efforts to determine the genesis of the extended post-primary attack latent period that characterizes infections with the majority of strains of P. vivax.

Animals↗

Activities of the tetrahydrofuran derivative, BA-41,799, against Plasmodium cynomolgi infections in rhesus monkeys.

BA-41,799, a tetrahydrofuran derivative that at one time attracted considerable interest as an antimalarial agent because of a combination of structural novelty with activities against infections with Plasmodium berghei and Plasmodium berghei yoelii in mice, has been evaluated for its capacities to effect prophylaxis and radical cure in rhesus monkeys challenged or already infected with sporozoites of the drug-susceptible Ro strain or the pyrimethamine-resistant Ro/PM strain of Plasmodium cynomolgi, and for its capacity to effect suppressive cure of infections with trophozoites of these strains. At doses up to the maximum tolerated, BA-41,799 had only marginal activity against infections with the Ro strain and none against the Ro/PM strain. On the basis of past experiences, the above results suggest that BA-41,799 would have little to offer for prophylaxis, radical cure, or suppression of human infections with Plasmodium vivax.

Animals↗

Enhancement of the curative activity of primaquine by concomitant administration of mirincamycin.

Mirincamycin, a lincomycin derivative with unequivocal but limited activity against the pre-erythrocytic and persisting exoerythrocytic stages of Plasmodium cynomolgi, has been evaluated for capacity to enhance the radical curative potential of the conventional primaquine-chloroquine combination. Established infections with sporozoites of the above plasmodium in rhesus monkeys served this evaluation. The results showed that the dose of primaquine required for cure of 50% of active infections was reduced by one-half to two-thirds by coadministration with 2.5 mg of mirincamycin per kg, 1/16 the 50% curative dose of this lincomycin derivative when used in a mono-drug regimen. The dimensions of the enhancement of the curative activity of primaquine were inversely related to the size of the sporozoite inoculum. The smallest dose of mirincamycin productive of enhancement was 2.5 mg/kg; whether doses larger than 2.5 mg/kg would have been more effective was not determined. There is much to be done before it is known whether a mirincamycin-primaquine combination is useful for suppressive cure or radical cure of the human malarias. Irrespective of that result, the current study serves to focus attention on a somewhat novel approach to the development of more effective and better-tolerated regimens for radical cure, an alternative to the empirical chemical synthesis and screening approach that has dominated searches heretofore.

Animals↗

Antimalarial activities and subacute toxicity of RC-12, a 4-amino-substituted pyrocatechol.

RC-12 [1,2-dimethoxy-4-(bis-diethylaminoethyl)-amino-5-bromobenzene] was evaluated for prophylactic, radical curative, and suppressive activities against infections with Plasmodium cynomolgi and subacute toxicity in rhesus monkeys. Applied as a prophylactic agent, RC-12, administered in doses of 6.25 to 25.0 mg/kg daily throughout the incubation period, provided near-complete to complete protection against 10(5) to 10(6) times the minimum infective dose of sporozoites. Applied as a suppressive agent, daily doses of 100.0 mg of RC-12 per kg did not eradicate blood schizonts regularly; hence, the need for concomitant administration of a blood schizonticide, such as chloroquine, in assessments of radical curative activity. In such appraisals, daily doses of 6.25 to 25.0 mg of RC-12 per kg for 14 days, in combination with 2.5 mg of chloroquine per kg daily for 7 days, effected cure of 69 and 93% of established infections, respectively. The curative activity of RC-12 was related to the total dose and could be achieved with a regimen as brief as 4 days. With respect to outward expressions of toxicity, daily doses of 50.0 mg/kg or lower for 15 to 225 days evoked no reactions. Doses of 100.0 or 200.0 mg/kg, scheduled for 15 days, evoked convulsions and depression and were, respectively, lethal to 4 of 17 and 7 of 7 recipients. Doses of 25.0 mg/kg or lower evoked no discrete reactions. Doses of 50.0 mg/kg and higher evoked hepatomegaly, vacuolation of hepatocytes, and elevations of glutamic oxalacetic and glutamic pyruvic transferase activities in serum, reactions related in intensity to dose but not duration of dosage.

Animals↗

Activities of respository preparations of cycloguanil pamoate and 4,4'-diacetyldiaminodiphenylsulfone, alone and in combination, against infections with Plasmodium cynomolgi in rhesus monkeys.

The studies summarized in this report were concerned with the capacities of repository preparations of cycloguanil pamoate (CGT-P) to protect rhesus monkeys against infections with drug-susceptible and pyrimethamine-resistant strains of Plasmodium cynomolgi. Administered intramuscularly as a suspension in an oleaginous vehicle, CGT-P (i) provided long-term protection against single and repetitive challenges of rhesus monkeys with sporozoites of the drug-susceptible B and Ro strains, (ii) effected prompt clearance of parasitemia in established infections, and (iii) delayed relapse. Protection was equated to absence of parasites on thick blood films, negative results when blood was transferred to susceptible recipients, and inability to activate infection by splenectomy. Eventual loss of protection was not related to emergence of parasites resistant to cycloguanil (CGT). Although protection varied from monkey to monkey, its mean duration was related directly to size of CGT-P dose and size of particles in the suspension. Urinary excretion studies indicated that protection persisted as long as the daily output of CGT did not fall below that attained with the parenterally administered hydrochloride salt at a dose equivalent to 0.015 mg of CGT per kg. Studies on infections with the resistant Ro/PM strain showed that the activity of CGT-P was compromised severely by resistance to pyrimethamine. Attempts to minimize this liability by concomitant administration of 4,4'-diacetyldiaminodiphenylsulfone met with limited success. These results suggest that even the best of the repository preparations of CGT-P, with or without 4,4'-diacetyldiaminodiphenylsulfone, would be useful only in areas where Plasmodium falciparum and Plasmodium vivax are fully susceptible to chlorguanide and pyrimethamine.

Acedapsone↗

Relationships between chemical structures of 8-aminoquinolines and their capacities for radical cure of infections with Plasmodium cynomolgi in rhesus monkeys.

Evaluation of 200 8-aminoquinolines for the capacities to effect radical cure of infections with sporozoites of Plasmodium cynomolgi in rhesus monkeys led to identification of 34 derivatives with activity equal or superior to that of primaquine and to characterization of substituents on the quinoline nucleus and side chain that favored or prejudiced curative activity. Of the 34 derivatives, 19 were as active as primaquine, 9 were twice as active, and 6 were four times as active. With respect to nuclear substituents, all were methoxy substituted at position 6; 24 had one and 10 had two additional substituents. The additions with most favorable impact on activity included methyl substituents at positions 4 and 2 and alkoxy, fluoro, and a group of 3- or 4-substituted phenoxy substituents at position 5. With respect to 8-amino substituents, 14 of the 15 derivatives more active than primaquine, and 13 of the 19 as active as primaquine, carried a branched alkyl chain, four to five carbons in length, between the 8- and terminal amino groups. Proximity of branching to the 8-amino group could be an important determinant of curative activity; however, the effect of such branching was not predictable. All 15 derivatives more active than primaquine and a substantial fraction of those comparable to primaquine in activity have sufficient structural novelty to merit evaluation for tolerability and radical curative activity in humans, with reasonable prospects that one or more would be better tolerated than primaquine and superior to this drug for cure of Plasmodium vivax infections.

Aminoquinolines↗

Appraisals of compounds of diverse chemical classes for capacities to cure infections with sporozoites of Plasmodium cynomolgi.

Compounds (265) of widely diverse structures were appraised for radical curative activity in rhesus monkeys infected with sporozoites of the B strain of Plasmodium cynomolgi, using an evaluation system that provided a preliminary assessment with from 0.1-1.0 g of compound and tests against one to five active infections. None of 32 compounds in a miscellaneous structure category, none of seven agents of antibiotic origin, none of 12 1,5-naphthyridines, and none of seven 7-aminoquinolines exhibited curative activity at the largest test doses. There was a suggestion that one of 12 newly synthesized pyrocatechols was curative. Two of 20 6-aminoquinolines effected cure at or near maximum tolerated doses. In contrast, 90 of 174 newly synthesized 8-aminoquinolines effected cure; 18 of the 90 being as active as primaquine, eight twice as active, and six four times as active. There were major disagreements between the above results and those recorded by others in mice inoculated with sporozoites of P. berghei yoelii or P. yoelii nigeriensis. These discrepancies were of serious dimensions in evaluations of the 8-aminoquinolines. This, plus previous near flawless performances of P. cynomolgi in identifying agents that would cure naturally acquired P. vivax infections, led to the suggestion that the abbreviated simian model employed in these studies be used hereafter in primary screening of new agents for radical curative activity.

Aminoquinolines↗