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Biomedical subjects

J Lundgren

Publications and source records attributed to J Lundgren.

At least 19 recordsLinked to original sources
PubMed1992

Frontal cortex lesion prior to hyperglycemic ischemia: no decrease in ensuing substantia nigra pars reticulata damage or fatal post-ischemic seizures.

Preischemic hyperglycemia worsens brain damage after ischemia, and characteristically leads to post-ischemic seizures and a pan-necrotic lesion in substantia nigra pars reticulata (SNPR). The excitatory input to SNPR could contribute to the damage observed. By performing a unilateral frontal cortex lesion 6-19 days prior to the ischemia, we wanted to explore whether a decrease in excitatory input to the ipsilateral SNPR ameliorate the seizures or alter the light microscopical damage in SNPR. Our results demonstrate that unilateral frontal cortex lesion did not alter the development of fatal post-ischemic seizures after 10 min of ischemia in hyperglycemic subjects. Thus, 7/8 animals developed seizures and died within 20 h of recovery. This study also failed to show any difference between the left and right side in post-ischemic SNPR damage after 15 h of recovery in animals with preischemic unilateral frontal cortex lesion. Furthermore, no side difference was observed in any other brain region evaluated. The results thus suggest that the pan-necrotic lesion in SNPR after hyperglycemic ischemia is not caused by excessive excitatory input from frontal cortex. A decrease in the GABA-ergic inhibitory input from caudoputamen to SNPR may be a more important mechanism for the ensuing excitotoxic post-ischemic SNPR damage, and for seizure development.

Amino Acids↗
PubMed1992

Effects of dimethylthiourea on ischemic brain damage in hyperglycemic rats.

Hyperglycemia is known to worsen the outcome of transient global or forebrain ischemia. The aggravating effect is believed to be mediated by the additional formation of lactate- and of H+. Recent evidence suggests that reactive oxygen species contribute to the damage after brain ischemia. Since acidosis accelerates free radical damage in vitro, we decided to explore if ischemic damage in hyperglycemic subjects is ameliorated by dimethylthiourea (DMTU), an established free radical scavenger. In one series of hyperglycemic rats, we studied whether preischemic administration of DMTU alters the clinical outcome, notably the incidence and frequency of seizures. In two different series, the effect of DMTU on tissue damage was assessed by light microscopy after 15 h of recovery. Longer periods could not be studied since seizures developed. In the first of these series the animals were anesthetized with isoflurane, and in the second with halothane. The latter anesthesia largely suppressed the "early" postischemic seizures, i.e. those occurring after 1-4 h. Dimethylthiourea treatment altered the clinical outcome after ischemia. Thus, the "late" postischemic seizures appeared milder and occurred significantly later than in untreated animals. The fatal outcome was also delayed since treated animals died after 35.5 +/- 8.2 h (mean +/- SD) of recirculation, as compared to 19.8 +/- 3.6 h of recirculation in control animals. However, all DMTU-treated (and control) animals died. In the first morphological series (isoflurane anesthesia) the histopathological analysis was complicated by the occurrence of prefixation seizures; such seizures were recognized in 4/16 animals. When these 4 animals were excluded from the analysis (2 treated and 2 control animals), DMTU pretreatment did not ameliorate the damage, except in the substantia nigra pars reticulata (P < 0.05). In the second series, comprising animals anesthetized with halothane, only one animal out of 16 had "early" seizures, and none showed "late" seizures before death. Among these animals DMTU treatment significantly ameliorated damage to caudoputamen and cingulate cortex (P < 0.01). We conclude that treatment with the free radical scavenger DMTU partly ameliorates ischemic brain damage associated with excessive acidosis, and marginally delays the development of post-ischemic seizures. However, the effects were moderate and could, at least in part, have been caused by nonspecific effects of DMTU. Furthermore, all DMTU-treated animals died. The results thus give little support to the notion that the aggravating effects of acidosis is due to enhancement of free radical production.

Animals↗
PubMed1992

Ischemic brain damage is not ameliorated by 1,3-butanediol in hyperglycemic rats.

BACKGROUND AND PURPOSE: Treatment with the ketone body precursor 1,3-butanediol has been suggested to ameliorate hypoxic/ischemic brain damage. Butanediol could provide an alternative energy substrate for the brain, thereby decreasing the amount of glycolytically produced lactate. Hyperglycemia aggravates brain damage after brain ischemia and causes fatal postischemic seizures, probably by increasing the production of lactate and decreasing the pH. We studied whether butanediol treatment altered the adverse consequences following ischemia complicated by hyperglycemia. METHODS: Hyperglycemic adult male rats were given 25 or 50 mmol.kg-1 body wt butanediol intravenously 30 minutes before 10 minutes of transient forebrain ischemia. Morphological evaluation was performed following perfusion-fixation after 15 hours of recovery. Blood concentrations of beta-hydroxybutyrate, acetoacetate, glucose, and lactate and brain tissue concentrations of energy metabolites were measured before and after ischemia. RESULTS: Blood levels of ketone bodies increased in the butanediol-treated rats. Ischemia decreased the blood levels of acetoacetate but increased the levels of beta-hydroxybutyrate by a similar amount, resulting in unchanged high levels of total ketone bodies in the animals that received butanediol. Brain tissue levels of glucose, energy metabolites, and lactate showed no difference between butanediol- and saline-treated rats. Furthermore, compared with saline-treated animals butanediol-treated rats showed no decrease in brain damage and no attenuation in the development of postischemic seizures. CONCLUSIONS: The ketone body precursor 1,3-butanediol offers no protective effect in transient forebrain ischemia complicated by hyperglycemia.

Animals↗
PubMed1991

Influence of moderate hypothermia on ischemic brain damage incurred under hyperglycemic conditions.

Preischemic hyperglycemia aggravates brain damage following transient ischemia, and adds some special features to the damage incurred, notably a high frequency of postischemic seizures, cellular edema, and affectation of additional brain structures, such as the substanta nigra pars reticulata (SNPR). We raised the question whether mild intra-ischemic hypothermia (32-33 degrees C), known to reduce selective neuronal vulnerability in normoglycemic subjects, also ameliorates the characteristic damage observed in hyperglycemic animals. To that end, two series of experiments were performed. In the first, normo- and hypothermic animals were subjected to 10 min of ischemia during hyperglycemic conditions (plasma glucose 20-25 mmol.l-1), and allowed either 15 h or 1 week of recovery. In the second, both normo- and hyperglycemic animals were subjected to 15 min of ischemia (at normal or reduced temperature) and surviving animals were studied after 1 week of recovery. All normothermic, hyperglycemic animals developed postischemic seizures and died within the first 24 h. Mild hypothermia afforded substantial protection. Thus, 6/7 hypothermic animals subjected to 10 min of ischemia survived 1 week of recovery and none developed post-ischemic seizures. Of the hypothermic animals subjected to 15 min of ischemia 6/11 survived for 1 week, only one of which developed seizures. Protection by hypothermia was also shown by the histopathological analysis. Experiments with 10 min of ischemia and 15 h of recovery showed the expected damage in normothermic, hyperglycemic subjects. Hypothermia markedly reduced damage in all vulnerable structures, including the cingulate cortex and SNPR. The protection was most pronounced in the caudoputamen, where no affected neurons were seen in the hypothermic subjects. The experiments with 15 min of ischemia confirmed previous findings that mild hypothermia protects normoglycemic animals against the insult. The results also showed that hypothermia prevented most of the exaggeration of damage caused by hyperglycemia. However, under hypothermic conditions hyperglycemia still augmented damage in the cingulate cortex, medial and lateral venteroposterior thalamic nuclei, and SNPR, structures specifically damaged under hyperglycemic, normothermic conditions. This suggests that hypothermia has less of a protective effect on mechanisms causing such damage than on neuronal damage in the classic selectively vulnerable regions, particularly the caudoputamen.

Animals↗
PubMed1991

Neurogenic sarcoma of the sinonasal tract.

Five cases of a rare malignant sinonasal tumour of neurofibromatous nature are described. The term neurogenic sarcoma (or malignant peripheral nerve sheath tumour) is advocated instead of malignant schwannoma. The clinicopathological features of this tumour are described, and the different diagnosis are discussed. The necessity of using immunohistochemistry in the diagnosis of sinonasal tumours of fibromatous nature is emphasized. The clinical management consists of radical surgery and adjuvant radiotherapy. Clinically there seems to be a high-grade and a low-grade type of sinonasal neurogenic sarcoma, however, this could not be distinguished histologically in the present series.

Adult↗
PubMed1991

Acidosis-induced ischemic brain damage: are free radicals involved?

Substantial evidence exists that reactive oxygen species participate in the pathogenesis of brain damage following both sustained and transient cerebral ischemia, adversely affecting the vascular endothelium and contributing to the formation of edema. One likely triggering event for free radical damage is delocalization of protein-bound iron. The binding capacity for some iron-binding proteins is highly pH sensitive and, consequently, the release of iron is enhanced by acidosis. In this study, we explored whether enhanced acidosis during ischemia triggers the production of reactive oxygen species. To that end, enhanced acidosis was produced by inducing ischemia in hyperglycemic rats, with normoglycemic ones serving as controls. Production of H2O2, estimated from the decrease in catalase activity after 3-amino-1,2,4-triazole (AT) administration, was measured in the cerebral cortex, caudoputamen, hippocampus, and substantia nigra (SN) after 15 min of ischemia followed by 5, 15, and 45 min of recovery, respectively (in substantia nigra after 45 min of recovery only). Free iron in cerebrospinal fluid (CSF) was measured after ischemia and 45 min of recovery. Levels of total glutathione (GSH + GSSH) in cortex and hippocampus, and levels of alpha-tocopherol in cortex, were also measured after 15 min of ischemia followed by 5, 15, and 45 min of recovery. The results confirm previous findings that brief ischemia in normoglycemic animals does not measurably increase H2O2 production in AT-injected animals. Ischemia under hyperglycemic conditions likewise failed to induce increased H2O2 production. No difference in free iron in CSF was observed between animals subjected to ischemia under hyper- and normoglycemic conditions. The moderate decrease in total glutathione or alpha-tocopherol levels did not differ between normo- and hyperglycemic animals in any brain region or at any recovery time. Thus, the results failed to give positive evidence for free radical damage following brief periods of ischemia complicated by excessive acidosis. However, it is possible that free radical production is localized to a small subcellular compartment within the tissue, thereby escaping detection. Also, the results do not exclude the possibility that free radicals are pathogenetically important after ischemia of longer duration.

Acidosis↗
PubMed1990

Preischemic hyperglycemia and postischemic alteration of rat brain pyruvate dehydrogenase activity.

Transient cerebral ischemia in normoglycemic animals is followed by a decrease in glucose utilization, reflecting a postischemic cerebral metabolic depression and a reduction in the activity of the pyruvate dehydrogenase complex (PDHC). Preischemic hyperglycemia, which aggravates ischemic brain damage and invariably causes seizure, is known to further reduce cerebral metabolic rate. To investigate whether these effects are accompanied by changes in PDHC activity, the postischemic cerebral cortical activity of this enzyme was investigated in rats with preischemic hyperglycemia (plasma glucose 20-25 mM). The results were compared with those obtained in normoglycemic animals (plasma glucose 5-10 mM). The activated portion of PDHC and total PDHC activity were measured in neocortical samples as the rate of decarboxylation of [14C]pyruvate in crude brain mitochondrial homogenates after 5 min, 15 min, 1 h, 6 h, and 18 h of recirculation following 15 min of incomplete cerebral ischemia. In normoglycemic animals the fraction of activated PDHC, which rises abruptly during ischemia, was reduced to 19-25% during recirculation compared with 30% in sham-operated controls. In hyperglycemic rats the fraction of activated PDHC was higher during the first 15 min of recirculation. However, after 1 and 6 h of recirculation, the fraction was reduced to values similar to those measured in normoglycemic animals. Fifteen of 26 rats experienced early (1-4 h post ischemia) seizures in the recovery period. The PDHC activity appeared unchanged prior to these early postischemic seizures. We conclude that the accentuated depression of postischemic metabolic rate observed in hyperglycemic animals is not coupled to a corresponding postischemic depression of PDHC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Ischemia in normoglycemic and hyperglycemic rats: plasma energy substrates and hormones.

Seizures are a documented complication to cerebral ischemia. After 10 min of forebrain ischemia in rats, preischemic hyperglycemia invariably leads to severe, most often fatal epileptic attacks. This outcome is related to the exaggerated lactic acidosis, which has been suggested as a possible contributor to severe membrane changes and widespread edema. To find out if circulating hormones or plasma energy substrates modulate this additive damage caused by the hyperglycemia, plasma concentrations of of corticosterone, epinephrine, norepinephrine, dopamine, glucagon, insulin, glucose, free fatty acids (FFA), 3-hydroxybutyrate, and acetoacetate were measured before and in the early recirculation period after 15 min of forebrain ischemia in the rat. Plasma corticosterone levels did not differ between the normo- and hyperglycemic groups. Although not significantly different from control, the catecholamine levels showed a tendency to be higher in the hyperglycemic groups. Therefore, because catecholamines have been reported to have a protective effect during ischemia the present result cannot explain why hyperglycemia aggravates the ischemic damage. Insulin levels seemed to increase during ischemia but not significantly. Levels quickly returned to normal after 30 min of recirculation. FFA concentrations were reduced after the induction of ischemia and appeared lower in all hyperglycemic groups. The level of one of the ketone bodies, 3-hydroxybutyrate, showed a significant decrease in hyperglycemic ischemia in all groups compared with normoglycemic ischemia. The same tendency was seen for acetoacetate. Results are compatible with a protective role of ketone bodies in ischemia. It is concluded that among the hormones and substrates studied only the ketone body concentrations qualify as a modulator of the exaggerated brain damage after ischemia in hyperglycemic subjects.

Animals↗
PubMed1989

Clear cell odontogenic carcinoma: report of three cases with pulmonary and lymph node metastases.

Three cases of a newly described rare odontogenic tumor are reported. One patient died with pulmonary metastases, one had an associated odontogenic cyst and one exhibited regional lymph node metastasis. The cases lend support to the odontogenic origin and metastatic capability of the clear cell odontogenic tumor. The authors recommend aggressive therapy and believe that the tumor should be considered a clear cell odontogenic carcinoma.

Aged↗
PubMed1987

Malignant tumours in patients with non-invasive squamous cell lesions of the vocal cords.

The concept of 'field cancerization' is applicable throughout the upper aerodigestive tract, oesophagus and lung. The material for this study consisted of 232 patients with hyperplasia, keratosis with or without dysplasia, and carcinoma in situ of the vocal cords. The overall risk for these patients with non-invasive squamous cell lesions of the vocal cords to have or to develop an independent, primary malignant tumour was 12.9% (30/232). Carcinomas of the head and neck, lung or oesophagus were diagnosed in 8.2% (19/232) of the patients. Patients with hyperplasia, keratosis, dysplasia and carcinoma in situ of the vocal cords should be carefully followed-up, not only as progression to invasive carcinoma may occur many years after the initial diagnosis, but also as there is a high incidence of independent primary tumours, especially of the multicentric type.

Carcinoma in Situ↗
PubMed1987

Aminolaevulinate dehydratase porphyria in infancy. A clinical and biochemical study.

Homozygous deficiency of aminolaevulinate dehydratase (porphobilinogen synthase, EC 4.2.1.24) was diagnosed in a small child. The clinical presentation was unique since severe symptoms were already present in the neonatal period. The patient, a boy, now three-years old, had recurrent attacks of pain, vomiting, hyponatraemia and symptoms of polyneuropathy engaging motor functions including respiration. The clinical course of the disease from birth on is related, as are the results of various attempts at therapy. The patient excreted large amounts of 5-aminolaevulinic acid and coproporphyrin and minor amounts of porphobilinogen in the urine. Faecal excretion of coproporphyrin and harderoporphyrin was increased as was erythrocyte porphyrin concentration. Diagnosis was established by the finding that erythrocyte aminolaevulinate dehydratase activity was less than 5 per cent of normal in the patient and between 26 and 51 per cent of normal in both the parents, the grandfathers and a sibling. The activity of the enzyme could not be restored by the addition of dithiothreitol (10(-3) mol/l) alone, or in combination with zinc or manganese in varying concentrations. The enzyme Km did not differ between affected and nonaffected members of the family.

Aminolevulinic Acid↗
PubMed1987

The effects of endorphins on mucous glycoprotein secretion from feline airways in vitro.

The effect of opioid peptide hormones on respiratory glycoprotein secretion was investigated in a cat tracheal organ culture system. Dynorphin A (dyn, 10(-5) M), alpha-endorphin (alpha E, 10(-5) M) and morphine sulfate (MS, 10(-4) M) stimulated mucous glycoprotein (MGP) release from airways, whereas all other endorphins tested failed to have such an effect. Dyn did so in a dose dependent manner (10(-5)-10(-7) M) with a peak effect after a one hour incubation. Two sets of data suggest that dyn is acting through the previously described endorphin-kappa receptor: The active binding site of dyn is at the carboxyl end of the peptide; dyn fragment 1-13 stimulated MGP secretion while dyn fragment 1-8 did not. Naloxone in equimolar concentration totally inhibited the dyn response. We, therefore, conclude that the endorphins dyn and alpha E stimulate MGP release and that dyn is probably acting by stimulating kappa receptors.

Animals↗
PubMed1987

Enzymatic defect in a child with hereditary hepatic porphyria due to homozygous delta-aminolevulinic acid dehydratase deficiency: immunochemical studies.

Immunochemical studies of the enzyme defect in the first reported child with acute hepatic porphyria due to homozygous delta-aminolevulinic acid dehydratase deficiency are described. This enzyme activity was markedly decreased (approximately 2% of the normal control level) in the proband, a 3-year-old boy, and intermediately decreased (23% to 57%) in both parents, in both grandfathers, and in a sister, but it was normal in two siblings and in both grandmothers. In contrast to the profound decrease in delta-aminolevulinic acid dehydratase activity, the immunoreactive enzyme protein in the child's erythrocytes was decreased to only 28% of the normal control level, suggesting the presence of positive cross-reactive material. In other family members with abnormally decreased delta-aminolevulinic acid dehydratase activity, and in the proband immediately after transfusion of normal RBCs, the positive cross-reactive material was not detectable. The immunochemical and enzyme activity data support the idea that delta-aminolevulinic acid dehydratase deficiency in this porphyric child is associated with the production of a catalytically abnormal enzyme protein.

Blood Proteins↗
PubMed1986

Hypertetraploid cells in vocal cord epithelia.

DNA measurements yield information about the nature of cells and may provide diagnostic and prognostic information. Static cytofluorometry was performed on smears removed at microlaryngoscopy from 107 vocal cord lesions (96 patients). All stem cell lines were diploid except 3; 2 carcinomas and 1 severe dysplasia were polyploid. The mean proliferative activity (percentage of nuclei greater than diploid peak) was 2.1% for the group of epithelia with hyperplasia and mild dysplasia, 3.1% for those with moderate dysplasia, 4.0% for severe dysplasia, and 6.8% for carcinomas. Hypertetraploid cell nuclei (HT cells) were not found in epithelia with hyperplasia and mild dysplasia. Seven out of 15 patients with epithelia showing moderate dysplasia had HT cells; 5 of these patients developed a carcinoma. One of 8 without HT cells developed a severe dysplasia. Nine patients with severe dysplasia had HT cells; 4 had recurrences and 4 developed carcinoma within 4 years. In 14 patients without HT cells, 3 had recurrences and 1 developed a carcinoma 6 years later. HT cells were found in 15 patients with T1 & T2 carcinomas; residual carcinoma was present in 2 after radiotherapy and 4 had recurrences within 11 months. Fourteen patients with T1 & T2 carcinoma did not have any HT cells; one had residual carcinoma after radiotherapy and 3 had recurrences between 18 months and 4 years. DNA measurements and, especially, the demonstration of epithelia with HT cells prove to be of prognostic importance.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma↗
PubMed1986

Multiple primary malignancies in patients treated for laryngeal carcinoma.

Multiple primary malignancies were found in 32 of 295 consecutive patients (10.8%) treated for carcinoma of the larynx. Synchronously developing second primary lesions were found in four patients while metachronously presenting lesions were diagnosed in 28. Second and third primary tumors were most commonly found in the larynx (11 patients, all with extralaryngeal index lesions) and lung (11 patients). The results of this retrospective study confirm the high incidence of multicentric neoplasia in the upper aero-digestive tract, lungs and esophagus. The rationale for including broncho-esophagoscopy in the evaluation of patients with laryngeal index tumors is discussed.

Adult↗
PubMed1979

Toluidine blue. An aid in the microlaryngoscopic diagnosis of glottic lesions?

The value of toluidine blue staining in vivo in the diagnosis of glottic lesions was examined by comparing the results obtained in a series with the histological findings. This material included 272 biopsy specimens from the vocal cords (202 microlaryngoscopic examinations). In 148 of these, the changes were classified as "malignant" (moderate and severe dysplasia and carcinoma) and in 124 as "benign." The sensitivity of the staining test in detection of malignant lesions was 91%. Among 13 false-negative results (9% of the malignant group), there was keratosis in 11. The overall specificity of the staining tests was 52%. The false-positive lesions displayed "benign" pathological alterations, such as inflammation and ulceration. False-positive findings were more common after radiotherapy. A correct diagnosis of malignancy on the basis of positive staining was more frequent the greater the intensity of staining.

Aged↗