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Biomedical subjects

C Frank

Publications and source records attributed to C Frank.

At least 163 records · Page 9Linked to original sources

Plasma and tumor tissue pharmacology of high-dose intravenous leucovorin calcium in combination with fluorouracil in patients with advanced colorectal carcinoma.

Plasma pharmacokinetics of high-dose (500 mg/m2) leucovorin calcium (dl-5-formyltetrahydrofolic acid [dl-CF]) and fluorouracil (FUra) have been evaluated in patients with advanced colorectal cancer treated with the combination of FUra and dl-CF by two different intravenous (IV) schedules: (A) In patients with no prior chemotherapy, dl-CF was administered by a two-hour IV infusion and FUra by rapid IV injection one hour after the start of the dl-CF infusion and (B) in previously treated patients, dl-CF and FUra were administered by five-day continuous IV infusion (CI). Following the two-hour infusion of dl-CF, mean peak plasma concentration and elimination half-life of I-5-formyltetrahydrofolic acid (I-CF) were 24 +/- 6 mumol/L and 0.8 +/- 0.1 hour, respectively. CI of dl-CF over five days yielded a mean steady-state plasma level of I-CF of only 1.2 +/- 0.5 mumol/L. Peak and steady-state plasma concentrations of the metabolite 5-methyl tetrahydrofolic acid were comparable in the two schedules (17 +/- 8 mumol/L for the two-hour infusion and 12 +/- 5 mumol/L for the CI). Areas under the concentration v time curve (AUC) of total reduced folates were significantly greater under conditions of CI: 89.0 v 16.7 mmol/L/min for the two-hour infusion. In tumor tissue, 5,10-methylenetetrahydrofolate increased eight-fold two to four hours following the two-hour infusion and two-fold during the CI of dl-CF and FUra. Inhibition of thymidylate synthase (dTMP-S) by the two-hour and CI infusion schedules were 66% v 39%, respectively. The observed differences in the intracellular dTMP-S folate cofactor pools and the degree of inhibition of dTMP-S achieved in patients treated by two different schedules may be due to differences in the biochemical properties and/or to differences in the modulation of FUra metabolism by folate of tumor tissues obtained from newly diagnosed and previously treated patients.

Antineoplastic Combined Chemotherapy Protocols↗

Lateral substitution for chronic isolated anterior cruciate ligament deficiency.

Thirty-five patients who had been surgically treated for major symptomatic isolated chronic anterior cruciate ligament deficiency by lateral extra-articular reconstruction alone were reviewed at an average of five years after operation. Seventy-seven per cent of patients reviewed were improved subjectively, and 83% of patients who were examined had objective evidence of only minor instability or none at follow-up. However, only a few patients had "normal" knees and many continued to have minor symptoms of instability with some restriction of activity. Most of the unsatisfactory results were in patients with significant chondral pathology at the time of reconstruction. While an extra-articular pivot-shift repair did not correct all the symptoms and signs completely, most patients were improved subjectively and objectively, and there were few complications.

Adolescent↗

Biochemical heterogeneity within the maturing rabbit medial collateral ligament.

The purpose in this investigation was to determine the biochemical composition of the normal rabbit medial collateral ligament (MCL) along its length during growth and maturation. Water content and hexosamine concentration as an index of glycosaminoglycan content and collagen concentration were quantified and results compared statistically for anatomically identified MCL segments at various ages. These data demonstrate differences in all parameters at different locations along the ligament and at different ages. Biochemical differences were noted between midsubstance and periinsertional areas. There were subtle differences between the two insertion sites of this ligament at all ages. These results indicate that the rabbit MCL is not homogeneous biochemically along its length and that its matrix composition changes with growth and maturation.

Aging↗

Effects of ketamine and (+)cyclazocine on 4-aminopyridine and "magnesium free" epileptogenic activity in hippocampal slices of rats.

The effects of ketamine and (+)cyclazocine on three in vitro models of epilepsy: the "Mg2+ free", the 4-aminopyridine (4-AP) and, for comparison, the penicillin model were studied. These data indicate that the two compounds had an inhibitory effect in hippocampal slices of rats, bathed in "Mg2+ free" solution at a concentration that did not influence the basal field potential. They also had an inhibitory effect on the penicillin model, but at concentrations ten times greater than those effective against "Mg2+ free" model. On the other hand, (+)cyclazocine was equally active against epileptogenic activity produced by 4-AP and "Mg2+ free" solution, while ketamine failed to produce an effect on epileptiform activity induced by 4-AP.

2-Amino-5-phosphonovalerate↗

Modulatory action of purinergic drugs on high potassium-induced epileptiform bursting in rat hippocampal slices.

Increase of the potassium concentration up to 8 mM in the superfused solution of rat hippocampal slices leads to the development of an epileptiform bursting. The derivative agonist L-phenyl isopropyl adenosine (L-PIA) (0.05-0.5 microM) is able to block the potassium induced epileptiform activity. The adenosine antagonist caffeine (100 microM) reverts the antiepileptic effect of L-PIA. Our data show a modulatory action of the purinergic transmission in a model of experimental in vitro epilepsy, and point out about a control of endogenous adenosine in the development of focal epileptiform activity. The relationships between the purinergic influence on the release of neurotransmitters, and the convulsant-anticonvulsant effects of the drugs are discussed.

Animals↗

Detection of low copy human papilloma virus DNA and mRNA in routine paraffin sections of cervix by non-isotopic in situ hybridisation.

In analysing human papilloma virus (HPV) infection of the cervix in formalin fixed paraffin sections by non-isotopic in situ hybridisation two main problems were found: detachment of sections from the glass during hybridisation and probe detection; inadequate sensitivity and inability to assess sensitivity of the in situ procedure. The first problem was investigated by assessing the efficiency of various tissue adhesives individually and in combination. The second problem was addressed by optimising conditions for DNA unmasking, hybridisation, and biotinylated probe detection. Sensitivity of the final in situ procedure developed was assessed by using the detection of pHY2.1 repeats as a built-in control. Extrapolation of data showed that less than 10 copies of HPV DNA can be visualised by these procedures. HPV nucleic acid, mainly in the form of DNA, was detected not only in koilocytic nuclei but also in suprabasal cells in condylomas and CIN lesions. HPV mRNA was also visualised in the cytoplasm (and probably also nuclei) of the same cell types. These non-isotopic in situ procedures give results comparable to those obtained with radiolabelled probes, but they are less time consuming and provide better morphological resolution.

Cervix Uteri↗

[Microbiology of ground water and drinking water].

Groundwater has been considered a safe source for drinking water protected against surface contamination. However, a number of reports about chemical and microbiological contamination have disproved this assumption. Besides hygienical monitoring, little is known about the microbiology of ground- and drinking water. The purpose of this paper is to give a review about the main fields of investigation concerning microbial activity in ground- and drinking-water-action. The hygienical relevant topics are: survival and transport of microorganisms, microbiological degradation of organic pollutants, turn-over of nitrogen compounds, oxidation and reduction of iron and manganese and development of methods for microbiological water examination.

Fresh Water↗

Accurate interpretation of the Lachman test.

In a consecutive series of patients with knee complaints, tibial rotation consistently affected the interpretation of the Lachman test (passive anterior tibial translation in slight knee flexion). To perform the Lachman test correctly, the anterior tibial force must be applied posteromedially on the proximal tibia. This is best achieved by having the leg under examination on the same side of the bed as the examiner, and with slight external tibial rotation. Reaching across the bed to examine either leg can create either false positive or false negative Lachman results due to inadvertent tibial rotation (internal tibial rotation decreases translation) and inaccurate comparisons of the injured and normal legs. The importance of tibial rotation must be recognized if the Lachman test is to be used reliably and with maximum sensitivity.

False Negative Reactions↗

[Forensic psychiatry problems in depression].

Forensic complications involving criminal or civil law are generally rare in depressive disorders, but are of varied nature and of great consequence to the person concerned. Suicide, which is the problem of greatest practical importance may have far-reaching consequences with regard to legal insurance, apart from the medical responsibility or liability. From the point of view of civil law, moreover, the effects of depression on thought and action, as well as on free will with respect to legal capacity, testifiability, marriageability, actionability and potential considerations of interdiction ought to be examined. Last, but not least, consequences of a socio-legal nature may ensue. The spectrum of possible crimes by depressed subjects essentially comprises disease-characteristic offences, amongst which the desperate deed of extended suicide is foremost, as well as other criminal acts with a less direct connection to the depressive syndrome. Additional factors such as alcohol and medication may further complicate the relationship and also the assessment of culpability. In the forensic judgment of depressed subjects diagnostic classification is not alone decisive, but depends to a greater extent on the nature and severity of the psychopathological state and its influence on motivational aspects.

Automobile Driving↗

[Psychological changes in multiple sclerosis].

In dealing with our multiple sclerosis (MS) patients concomitant and consecutive symptoms of a psychical nature also deserve appropriate consideration in addition to the variety of somatic symptoms. In the following synopsis, numerous and in part divergent findings - observations, hospital statistics as well as psychodiagnostic test results - concerning the psychopathology of MS are presented. A multiplicity of mental changes, depending upon the variability of the disease process and its course, can be noticed. Over the past century euphoria was long regarded as the psychopathological trait of MS. Along with transitions in patient populations in the meantime hardly more euphoric than depressive moods are registered. Euphoric mood aberrations are to be regarded as substrate dependent disturbances, which deteriorate parallel to disease duration and severity. Intellectual dysfunctions as well as topical brain symptoms (so-called "instrumental disabilities"), obsessive laughing and crying also reflect the basic organic process. Concerning other symptoms such as depression or dysphoria, emotional lability or lack of drive, at its extreme apathy, one cannot definitely determine to what extent - in view of a multidimensional approach - these are to be regarded as mental correlates of the disease process, or as individual reactions to the disease along with considerable social consequences. Psychoses, rarely occurring in MS, can be classified either as organic, or, in seldom cases, as a fortuitous coincidence of MS and endogenous psychosis.

Affective Symptoms↗

Normal ligament properties and ligament healing.

There is still a long way to go to achieve the goals of ligament replacement through modification of normal, intrinsic ligament healing processes. We are learning about the biology of ligamentous tissues, including the problem of regeneration, and that in itself is an all-important first step toward seeking solutions.

Biomechanical Phenomena↗

[Microbiological studies of groundwater polluted with hydrocarbons. 2. Determination of bacterial in vitro activity].

The injected water and the groundwater withdrawn by the E-wells contained bacteria with higher 'in vitro'-total activity (30-50%) than the groundwater taken from the middle part of the flushing area. The determination of single-activities resulted in a similar distribution of bacterial communities. Denitrifying and nitrate-reducing bacteria were present in the polluted groundwater (10-100% of isolates). After transforming these values in CFU/ml they correspond to the MPN/ml of both groups. Furthermore bacteria were found, which could use hydrocarbons as their only carbon source under aerobic and anaerobic conditions; there were different percentage of hydrocarbon-degrading bacteria in the groundwater of the three sampling points. Totally 2-70% of all isolates were aerobe hydrocarbon-degrading bacteria, 1-12% nitrate-reducing and 1-13% denitrifying hydrocarbon-metabolizing bacteria.

Aerobiosis↗

Tendons and ligaments: a morphological and biochemical comparison.

The purpose of this study was to compare selected rabbit tendons and ligaments morphologically and biochemically. Five representative structures from each of six age- and sex-matched rabbits were compared. Biochemical analyses included total collagen, reducible collagen cross-links, quantitative collagen typing, DNA, and glycosaminoglycans. Histological and chemical differences were demonstrated between the tendons and the ligaments. Smaller differences were also found between the individual ligaments (collateral and cruciate) and between the two tendons (patellar and Achilles) that were examined. These findings suggest that ligaments are more metabolically active than tendons, having more plump cellular nuclei, higher DNA content, larger amounts of reducible cross-links, and the presence of more type III collagen, as compared with tendons. They also contain slightly less total collagen than tendons and more glycosaminoglycans. We conclude that the tendons and ligaments studied have unique histological and biochemical characteristics, despite their gross similarities. Relatively increased metabolic activity in ligaments, implied by our findings, may be species specific, age related (transient), or may truly represent a structural expression of functional need for more rapid adaptation. Further investigation of other similarities or differences between particular ligaments (or tendons) is indicated, and attention is directed toward the importance of such variables in development of models for tendon and ligament studies.

Animals↗