[Lung computer tomography guided fine-needle biopsies].
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Adult↗
Biomedical subjects
P Nikula
Publications and source records attributed to P Nikula.
Auditing a nationwide vascular registry--the 4-year Finnvasc experience. Finnvasc Study Group.
OBJECTIVE: To assess the validity of a national vascular registry. MATERIALS AND METHODS: 17,465 vascular and endovascular procedures, immediate reoperations excluded, registered in the Finnvasc registry from 26 centres during the years 1991-1994. CHIEF OUTCOME MEASURES: Comparison of the number of registered procedures with hospital records, comparison of initial registrations with a random sample of re-registration and comparison of the 1-year local data input of one major centre to the same data input of the central unit. RESULTS: The rate of missing registrations was 19% ranging from 0-47%. The data of the re-registered forms were in agreement with the original data in 93% of all data points, the range being from 81-100%. There was a difference of 1.5% in the data between the major centre and the central unit. CONCLUSIONS: The Finnvasc registry makes it possible to audit vascular surgery nationally, although a potential limitation is centres with low registration rates.
Finland↗
Stress fractures of the olecranon in javelin throwers.
Between the years 1977 and 1984, four javelin throwers with a stress fracture of the olecranon were seen and treated. In one patient, acute painful dislocation of the fracture occurred during a competitive throw. Two patients had stress fracture of the tip. The fracture treated conservatively healed in 18 months. The patient treated by excision of the tip was able to throw after 2 months. Two patients had slightly oblique, more distally located stress fractures, which were treated with a tension band and 2 Kirschner wires. The fractures healed in 4 months. One of the patients had a refracture 11 months after the primary operation. It was successfully treated with a compression screw and two bone pegs. Because of the high risk of delayed union and nonunion, stress fractures of the olecranon should be treated operatively in javelin throwers.
Adult↗
Effects of bis(guanylhydrazones) on the activity and expression of ornithine decarboxylase.
Derivatives of glyoxal bis(guanylhydrazone) (GBG), such as methylglyoxal bis(guanylhydrazone) and ethylglyoxal bis(guanylhydrazone), are potent inhibitors of S-adenosylmethionine decarboxylase (EC 4.1.1.50), the key enzyme required for the synthesis of spermidine and spermine. These compounds, but not the parent compound, induce a massive accumulation of putrescine, partly by blocking the conversion of putrescine into spermidine, but also by strikingly stimulating ornithine decarboxylase (ODC; EC 4.1.1.17) activity. The mechanism of the stimulation of ODC activity and enhanced accumulation of the enzyme protein apparently involved a distinct stabilization of the enzyme against intracellular degradation. However, although the parent compound GBG also stabilized ODC, it powerfully inhibited the enzyme activity and the accumulation of immunoreactive protein in cultured L1210 leukaemia cells. Kinetic considerations indicated that, in addition to the stabilization, all three compounds, GBG in particular, inhibited the expression of ODC. It is unlikely that the decreased rate of synthesis of ODC was attributable to almost unaltered amounts of mRNA in drug-treated cells, thus supporting the view that especially GBG apparently depressed the expression of ODC at some post-transcriptional level.
Animals↗
Carnitine prevents the early mitochondrial damage induced by methylglyoxal bis(guanylhydrazone) in L1210 leukaemia cells.
We previously found that the anti-cancer drug methylglyoxal bis(guanylhydrazone) (mitoguazone) depresses carnitine-dependent oxidation of long-chain fatty acids in cultured mouse leukaemia cells [Nikula, Alhonen-Hongisto, Seppänen & Jänne (1984) Biochem. Biophys. Res. Commun. 120, 9-14]. We have now investigated whether carnitine also influences the development of the well-known mitochondrial damage produced by the drug in L1210 leukaemia cells. Palmitate oxidation was distinctly inhibited in tumour cells exposed to 5 microM-methylglyoxal bis(guanylhydrazone) for only 7 h. Electron-microscopic examination of the drug-exposed cells revealed that more than half of the mitochondria were severely damaged. Similar exposure of the leukaemia cells to the drug in the presence of carnitine not only abolished the inhibition of fatty acid oxidation but almost completely prevented the drug-induced mitochondrial damage. The protection provided by carnitine appeared to depend on the intracellular concentration of methylglyoxal bis(guanylhydrazone), since the mitochondria-sparing effect disappeared at higher drug concentrations.
Animals↗
S-adenosylmethionine decarboxylase as target of chemotherapy.
Although ornithine decarboxylase under most conditions is the rate-controlling enzyme of polyamine biosynthesis and thus the most logical target for chemical intervention, the inhibition of the enzyme triggers a series of compensatory reactions all aimed to circumvent the inhibition. These include secondary induction of adenosylmethionine decarboxylase, enhanced accumulation of extracellular polyamines and an overproduction of ornithine decarboxylase resulting from enhanced expression and gene amplification. Thus chemotherapy based on an intervention of polyamine formation has also to be directed to reactions other than the decarboxylation of ornithine. Adenosylmethionine decarboxylase is the second natural target for chemotherapy. Virtually all effective inhibitors of this enzyme are members of the family of bis(guanylhydrazones). Small modifications, such as increased hydrophobicity at the glyoxal portion of the parent compound glyoxal bis(guanylhydrazone), greatly enhance the inhibition of adenosylmethionine decarboxylase and diminish the undesirable inhibition of diamine oxidase. However, although ethylglyoxal and propylglyoxal bis(guanylhydrazone) appear to utilize the putative polyamine carrier for their cellular entry, their cellular accumulation, in contrast to that of glyoxal and methylglyoxal bis(guanylhydrazone), is not stimulated by putrescine and spermidine deprivation produced by inhibitors of ornithine decarboxylase. It is obvious that the cellular accumulation of each of the bis(guanylhydrazones) is determined by their different efflux rates: GBG and MGBG are effectively retained whereas EGBG is rapidly excreted by the tumor cells. GBG and MGBG, but possibly not EGBG, behave as mitochondrial poisons and rapidly produce extensive morphological damage of the mitochondria. The bis(guanylhydrazones) likewise inhibit carnitine-dependent mitochondrial oxidation of long-chain fatty acids, competitively in respect to carnitine. It is possible that this inhibition has something to do with the mitochondrial damage, as carnitine protects tumor cells from the early mitochondrial damage produced by MGBG. Carnitine also protects experimental animals from MGBG-induced acute toxicity and death.
Adenosylmethionine Decarboxylase↗
Stress fracture of the fifth metatarsal in athletes.
Between 1975 and 1984 11 athletes with stress fractures of the fifth metatarsal were treated. There were 6 diaphyseal fractures, all of them in runners, and 5 transverse fractures of the base (Jones' fractures). The diaphyseal fractures healed with rest in 3-4 weeks. One patient with Jones' fracture was treated conservatively with a non-weight-bearing toe-to-knee plaster with good results. Four patients with delayed unions were treated operatively, three with a tension band and two Kirschnerwires, one with drilling and a single, thick Kirschner-wire. The fractures treated operatively progressed to bony union in about 3 months. The tendency of the Jones' fracture to delayed union and non-union in active athletes makes special requirements to the initial therapy of stress fractures. Best results have been obtained with a toe-to-knee cast with non-weight-bearing for 6-7 weeks. In delayed unions we recommend a tension band fixation with two Kirschner-wires. Non-unions should be treated with curettage and bone-grafting.
Adult↗
Inhibition of long-chain fatty acid oxidation by methylglyoxal bis(guanylhydrazone).
Methylglyoxal bis(guanylhydrazone) (MGBG), an inhibitor of spermidine and spermine biosynthesis and clinically used anti-cancer drug, powerfully inhibited carnitine-dependent fatty acid oxidation in heart muscle homogenates. Equipotent inhibition was also produced by spermine whereas spermidine and putrescine were less effective. MGBG appeared to act as a competitive inhibitor in respect to carnitine. Even though MGBG and spermine equally effectively depressed palmitate oxidation in muscle homogenates in vitro, a striking difference existed between the compounds as regards their effects on fatty acid oxidation in cultured tumor cells. Micromolar concentrations of MGBG distinctly impaired palmitate utilization also in cultured L 1210 leukemia cells, whereas similar concentrations of spermine markedly enhanced the oxidation of the fatty acid. The inhibitory effect of MGBG in cultured tumor cells was, at least partly, reversed upon addition of exogenous carnitine. The finding indicating that MGBG impairs fatty acid utilization may be an explanation for the known hypoglycemic effect produced by the drug in most animal species as well as for some of the side-effects associated with its clinical use, most notably severe myalgia.
Animals↗
Transfer of intestine-derived diamines into tumour cells during treatment of Ehrlich-ascites--carcinoma-bearing mice with polyamine anti-metabolites.
Treatment of Ehrlich-ascites-carcinoma-bearing mice with methylglyoxal bis(guanylhydrazone) alone or in combination with 2-difluoromethylornithine greatly enhanced the transfer of intragastrically administered radioactive putrescine and cadaverine into the carcinoma cells. Difluoromethylornithine alone did not have any effect on the accumulation of intestine-derived diamines in the tumour cells. The frequently reported restoration of difluoromethylornithine-induced polyamine depletion on administration of methylglyoxal bis(guanylhydrazone) is in all likelihood attributable to a profound inhibition of intestinal diamine oxidase (EC 1.4.3.6), resulting in an enhanced entry of intestinal (bacterial) diamines into general circulation and finally into tumour cells.
Animals↗