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Biomedical subjects

H Kostron

Publications and source records attributed to H Kostron.

At least 37 records · Page 2Linked to original sources
PubMed1990

Effect of the calcium entry blocker nimodipine on the metabolism of nucleic acids in rat brain ischemia.

The effect of nimodipine, a 1,4 dihydro-piridine calcium entry blocker (200 micrograms/kg), was investigated in rats after definitive ischemia or 2 min of global ischemia (neck tourniquet method). The brains were freeze-clamped at the desired time intervals and subjected to high pressure liquid chromatography analyses for nucleotides and enzymatic lactate estimation. Although in the definitive ischemia (removal of the brain) no difference was observed in the treated versus the untreated animals, there was a statistically significant difference in both groups after global ischemia followed by reperfusion. Thirty minutes after reflow the brains of the treated animals contained 1,690 +/- 62 nmol ATP/g as compared to 765 +/- 259 nmol ATP/g in the untreated animals (p less than 0.05). The normal controls amounted to 1,932 +/- 77 nmol ATP/g. Also the adenylate energy charge returned to normal in the treated animals (treated animals and controls 0.69 and 0.72, respectively). From these preliminary data we conclude that nimodipine is able to restore mitochondrial function after ischemia and to maintain a high level of energy-rich phosphates. Thus, calcium entry blockers may be effective in preserving and protecting cerebral tissue from irreversible injury after ischemia.

Adenine Nucleotides↗
PubMed1990

Pharmacokinetics of glucosteroids in severe head injury. Experimental studies in rat brain after cold lesion.

The treatment of brain edema after severe head injury remains controversial. We investigated the uptake kinetics and pharmacokinetics of glucocorticoids in rat brain after cold lesion, employing tritium-labeled dexamethasone or tritium-labeled triamcinolone acetonide (TA). The normal brain, as demonstrated on isolated cells, revealed a saturable, time-dependent uptake of dexamethasone (rate of uptake, 5 nm/mg protein/min at 37 degrees C). This clearly defined uptake is replaced by a simple diffusion like uptake after the trauma. The pharmacokinetical studies demonstrated a rapid decline of the TA concentration after a bolus injection in the brain tissue after the trauma. Within 30 min only 11% of the initial concentration could be discovered in the traumatized brain tissue. However, after a discontinuous administration of TA, a steady state was reached in the normal brain after 24 hr (0.26 micrograms TA/g). In the traumatized brain the concentration increased steadily amounting to 0.34 micrograms TA after 24 hr. The continuous infusion of TA resulted in an equal high concentration in normal brain than after the discontinuous administration. The continuous infusion of TA, however, produced the highest concentration of TA in the traumatized brain after 24 hr (0.79 micrograms TA/g) (p less than 0.05 as compared with the discontinuous injection). Our results demonstrate that the widely used discontinuous administration of steroids result in low tissue concentration, which might account partly for the low efficiency of steroids in traumatic brain edema. The continuous administration of the steroid TA increases the concentration in the traumatized tissue and might therefore be beneficial in the treatment of brain edema after severe head injury.

Animals↗
PubMed1989

[Space-occupying, traumatically-induced hemorrhage of the posterior cranial fossa].

A total of 4,408 patients were treated for head injuries from 1980 to 1986 at the University Hospital of Innsbruck in Austria. Nine of them (0.2%) showed a traumatic, space-occupying hematoma in the posterior fossa. Clinical signs are often elusive, but tentorial or foraminal herniation with apnea may suddenly arise. Heightened awareness of these lesions and closely monitoring these patients are both necessary, especially when there is a fracture over the transverse sinus or the foramen magnum. Computed tomography helps to establish the diagnosis and leads to appropriate neurosurgical treatment. The overall mortality of patients with these lesions was 22% in our patients.

Adult↗
PubMed1988

Photodynamic therapy is potentiated by Co60 and intratumoral injection of hematoporphyrin derivative.

Hematoporphyrin derivative injected directly into a subcutaneous rat glioma resulted in a significant greater tumor growth inhibition than hematoporphyrin derivative injected parenterally upon stimulation by light, Co60 or by combination of the above. The photodynamic effect was analyzed in an in vivo and in an in vitro clonogenic assay. The directly injected hematoporphyrin derivative without external activation inhibited tumor growth to 34%. Light and directly injected HPD inhibited tumor growth to 3%, whereas 4, 8 and 16 Gy of Co60 produced a growth inhibition to 11%, 0.05% and 0.00% respectively. This cytotoxic effect of the ionizing radiation is further potentiated by the addition of light, resulting in a growth inhibition to 0.1%, 0.00% and 0.00% respectively for the three corresponding radiation doses. The direct intratumoral injection of HPD minimizes the side effects and increases the effect of the photodynamic therapy as compared to the parenterally administered HPD. This direct injection modality could be of potential value in the treatment of human gliomas or other tumors.

Animals↗
PubMed1988

Acute spinal subdural haematoma.

A 55-year-old female was brought to our out-patient clinic with an initially ascending, acute hemiplegia. The following descending myelography and CT scan disclosed a mass lesion at C6-D4. The acute spinal subarachnoidal haemorrhage found at operation, its genesis, diagnosis, treatment and rehabilitation are discussed.

Anticoagulants↗
PubMed1988

The calcium entry blocker nimodipine improves the quality of life of patients operated on for cerebral aneurysms. A 5-year follow-up analysis.

Between 1981 and 1985 at our clinic 204 consecutive patients underwent surgical repair of cerebral aneurysms after spontaneous subarachnoid hemorrhage. Of these 113 were treated with Nimodipine, a predominantly cerebrovaskular-active substance. The preoperative condition according to Hunt and Hess (9), the locations of the aneurysms, and the ages of the two groups of patients were directly comparable. The incidence of postoperative cerebral vasospasm was however higher in the Nimodipine group (49%) than in the control group (33%). Retrospectively we analyzed the progress of the patients as to their neurological, intellectual, and social function for up to five years after the operation. Mortality and morbidity in the Nimodipine group amounted to 10% and 7% respectively, in the group without Nimodipine 20% and 17% respectively (p less than 0.001). Of the Nimodipine patients, 72% showed excellent neurological outcome, with 73% intellectually, and 72% completely resocialized, as compared to 53% in the control group with an excellent neurological outcome, 39% intellectually intact (p less than 0.0001, and 52% completely resocialized (p less than 0.01). These results suggest that Nimodipine not only increases cerebral blood flow, but also protects brain tissue from ischemic damage.

Activities of Daily Living↗
PubMed1988

Photodynamic therapy of malignant brain tumours: a phase I/II trial.

Twenty patients bearing malignant brain tumours (18 glioblastoma multiforme, one malignant meningioma, one melanoma metastasis) were treated 25 times with photodynamic therapy (PDT)--the combination of Hematoporophyrin derivative and light at 630 nm (40-120 J/cm2). Sixteen times the PDT was followed immediately by a single dose radiation of 4 Gy of fast electrons. Conventional radiotherapy following PDT was performed in eight patients. The median survival of three patients with multiple recurrences of glioblastoma grade IV and various chemo- and radiotherapy was 5 months. Four out of 10 patients with one recurrence and prior treatment died with a median survival of 5 months, six are still living up to 12 months. Six patients with a primary glioblastoma are surviving now up to 22 months. Phototoxicity to the skin, the only side effect of PDT, was noted in five cases, but did not pose any threat to the patients. The treatment did not affect the quality of life of the patients. Our preliminary results with the photodynamic treatment of malignant gliomas indicate that PDT might be a valuable addition to our armament in the treatment of such tumours.

Adult↗
PubMed1987

[Photodynamic therapy of malignant brain tumors].

The combination of haematoporphyrin derivative (HPD) and visible light at 630 nm, termed as photodynamic treatment (PDT), provides a new tool in tumour therapy, causing selective tumour destruction initiated by photochemical reactions. Up to now 13 patients with malignant brain tumours (12 glioblastoma multiforme, 1 leiomyosarcoma) were treated with 40-80 J/cm2 light following parenteral or direct injection of HPD (5 mg/i.a. or 1 mg/ccm tumour volume). In 5 patients the PDT was followed by subsequent radiotherapy with 4 Gy. The patients with recurrent tumour showed a median survival time of 5 months, whereas the 6 patients with primary manifestations have survived so far for periods of up to 9 months. However, the follow up period is too short to allow final conclusions to be reached on the effect of PDT in the treatment of malignant brain tumours.

Adult↗
PubMed1987

[Therapy of malignant brain tumors].

The operative removal of the tumour mass as early and completely as possible is the most important step in the treatment of malignant brain tumours, whereby the quality of life must be maintained as a prerequisite. The operation is followed by radiotherapy at a dosage of 60 Gy which again is followed by chemotherapy with CCNU and Oncovin. New strategies in chemotherapy, radiotherapy, hyperthermia and photochemotherapy will be evaluated over the coming years. The therapy of malignant brain tumours represents a universal challenge, and despite the only small increase in life span by 6-9 months, this must be considered a partial progress in the combat against brain tumours.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

The interaction of hematoporphyrin derivative, light, and ionizing radiation in a rat glioma model.

The effects of hematoporphyrin derivative, light, and cobalt 60 (60Co) irradiation were studied in a rat glioma model using an in vivo and an in vitro clonogenic assay. There was no effect on tumor growth by visible light or by a single dose of 60Co irradiation at 4 Gy or 8 Gy, whereas 16 Gy inhibited tumor growth to 40% versus the control. Hematoporphyrin derivative alone slightly stimulated growth (P less than 0.1). Light in the presence of 10 mg hematoporphyrin derivative/kg inhibited tumor growth to 32%. 60Co irradiation in the presence of hematoporphyrin derivative produced a significant tumor growth inhibition (P less than 0.02). This growth inhibition was directly related to the concentration of hematoporphyrin derivative. The addition of 60Co to light in the presence of hematoporphyrin derivative produced a greater growth inhibition than light or 60Co irradiation alone. This effect was most pronounced when light was applied 30 minutes before 60Co irradiation. Our experiments in a subcutaneous rat glioma model suggest a radiosensitizing effect of hematoporphyrin derivative. Furthermore, the photodynamic inactivation is enhanced by the addition of 60Co irradiation. These findings may be of importance in planning new treatment modalities in malignant brain tumors.

Animals↗
PubMed1986

Uptake kinetics and receptor binding of glucocorticosteroids in head injury: an experimental study in a rat brain oedema model.

The uptake of dexamethasone (DM), as well as the glucocorticoid receptors binding sites (GCR) were studied in normal rat brain and in the rat brain after cold lesion of the right hemisphere. DM was taken up at a rate of 5.05 nmol/mg prot./min. by isolated cells of normal brain. This uptake was concentration (saturation at 10(-4) DM) and time dependent (linear up to 10 min), but was not temperature dependent. Isolated cells derived from the cold lesioned brain demonstrated a process, which is unsaturable (diffusion like) and not time nor temperature dependent. The brains of adrenalectomized rats were assayed for the GCR. There was no marked difference in the GCR content of the cortex, white matter and brain stem. Within 6 h after the cold lesion the GCR concentration in the lesioned hemisphere increased significantly (p less than 0.05). This increase was followed by a slow-levelling-off within 2 days, to reach the control values again in 7 days. At the trauma site itself, the GCR were decreased (p less than 0.10), whereas the GCR were markedly increased in the remaining homolateral hemisphere (p less than 0.001). These results favour the use of steroids in the treatment of brain oedema following severe head injury despite the controversial results of various clinical trials.

Adrenalectomy↗
PubMed1986

Distribution, retention, and phototoxicity of hematoporphyrin derivative in a rat glioma. Intraneoplastic versus intraperitoneal injection.

The distribution, retention, and phototoxicity of the sensitizer hematoporphyrin derivative (HPD) were studied following intraperitoneal and direct intraneoplastic injections of the agent into subcutaneous or intracerebral gliosarcomas in rats. Forty-eight hours after intraperitoneal injection, the ratio of tritiated (3H) HPD in subcutaneous tumor: adjacent normal skin was about 1.4:1 and the ratio in tumor: normal brain was 3:1. In contrast, direct injection of 3H-HPD into subcutaneous tumors resulted in tumor: adjacent normal skin concentration ratios of approximately 44:1 and tumor: normal brain ratios of about 61:1. For rats bearing intracerebral gliosarcomas, intraperitoneal administration of 3H-HPD resulted in approximately 1.3-fold sensitization in tumor tissue relative to adjacent edematous brain. In contrast, after direct injection into intracerebral tumors, the tumor: adjacent edematous brain and tumor: skin 3H-HPD ratios were 3:1 and 32:1, respectively. In all cases, 3H-HPD was found in every portion of the tumor, even at a distance from the injection site. For the 3H-HPD doses used in this study, after direct injection both subcutaneous and intracerebral tumor tissue contained about three to four times more 3H-HPD than tumors in rats receiving intraperitoneal 3H-HPD. Both in vitro and in vivo clonogenic assays demonstrated that the photodynamic inactivation of the tumors was significantly greater after direct injection than after intraperitoneal injection.

Animals↗
PubMed1986

Diphenylhydantoin induced granulocytopenia following a seizure prophylaxis after a depressed skull fracture.

The article deals with a rare case of granulocytopenia following a seizure prophylaxis after a severe head injury. Although fatal complications like the one described occur extremely seldom, we want to emphasize the necessity of regular controls during the critical time period between the 10th and the 67th day of diphenylhydantoin treatment. The blood level should not exceed 10-20 micrograms/ml to prevent any toxic reaction to the myelopoetic system. If this treatment cannot be provided, we suggest to administer Clonazepam or Convulex.

Aged↗
PubMed1985

Treatment of cerebral vasospasm following severe head injury with the calcium influx blocker nimodipine.

8 patients suffering from severe head injury (Glasgow Coma Scale score of 3-5) were treated with the calcium influx blocker nimodipine (2-3 mg/h) for a traumatic cerebral vasospasm. In every case the spasm involved the frontal region of the circle of Willis with the first two segments of the anterior and middle cerebral artery. Control angiograms, recorded in 6 patients, revealed a dilated or normalized lumen of the vessels that the first angiography had revealed to be spastic. The intracranial and the mean arterial pressure were not altered by nimodipine during simultaneous neurosurgical intensive care therapy (dexamethasone, mannitol, relaxation, and controlled respiration for 2-3 days). Monitoring of the somato-sensory evoked potentials (SEP) showed a distinct improvement of the cortical response within 7 days. One patient died of sepsis 8 days after the accident and one remained in a vegetative state. The remaining patients reached Glasgow Coma Scale scores of 13.0 +/- 1.1. within 8.6 +/- 2.2 days, the initial scores having been 4.1 +/- 0.8. One year after their accident all the patients were once again fully able to work. The survival quality was therefore better than that reported in the literature for patients in similar conditions. We conclude from these preliminary results that calcium influx blockers can be used successfully in the therapy of traumatic vasospasm and of severe head injuries. A study involving a larger number of patients is currently in progress.

Adolescent↗