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Biomedical subjects

P Jacobsen

Publications and source records attributed to P Jacobsen.

At least 55 records · Page 3Linked to original sources
PubMed1996

Regional variations in neural tube defects and alfa-fetoprotein screening in Denmark 1983-88.

BACKGROUND: An effect of maternal serum alpha-fetoprotein screening on prevalence rates for neural tube defects (NTD's) has been demonstrated in some populations. The present study tests the hypothesis that regional rates in the Danish low risk population reflects screening activities. METHODS: Cross-sectional survey for neural tube defects through the Danish Malformation Register. RESULTS: The prevalence rate for all neural tube defects was 5.8 pr 10(4) births which is lower than in most other populations. Standardized risk ratios for NTD in two regions with a program for alfa-fetoprotein screening were 0.1 (95% c.i. 0.0-0.7) and 0.4 (95% c.i. 0.2-0.9). Relative risk at 0.6 (95% c.i: 0.4-1.1) was found in one county with screening of approximately one third of pregnancies. In most other counties < 5% of pregnant women had been examined and point estimates of relative risks varied from 0.9-1.7. CONCLUSION: There was a good agreement between prevalence of neural tube defects at birth and regional alfa-fetoprotein screening activity. This can be taken as a strong indication of a secondary preventive effect from screening in a population with a priori low risk for NTD's. However, other aspects of screening should also be taken into consideration before general programs are forwarded.

Biomarkers↗
PubMed1996

The acute effect of smoking on systemic haemodynamics, kidney and endothelial functions in insulin-dependent diabetic patients with microalbuminuria.

The acute effect of smoking upon arterial blood pressure, urinary albumin excretion rate, glomerular filtration rate and transcapillary escape rate of albumin were investigated in nine normotensive insulin-dependent diabetic patients with microalbuminuria, who had been smoking for 19 (range 4-30) years. In a prospective, open randomized cross-over design, patients were investigated with and without smoking three cigarettes per hour during a 5.5-h period. A rise in systolic blood pressure and heart rate (Takeda TM2420, median (range)) was observed during the smoking day (10(-11 to 14) mmHg and 8 (-1 to 19) beats min-1), compared to the non-smoking day (1 mmHg (-7 to 13) (p = 0.05) and 0 beats min-1 (-2 to 4) (p < 0.01)). Urinary albumin excretion rate (ELISA), glomerular filtration rate (plasma clearance of 51Cr-EDTA) and transcapillary escape rate of albumin (125I-albumin) remained the same with or without smoking. Our study suggests that heavy smoking induces an abrupt rise in systolic blood pressure and heart rate, while vascular leakage of albumin and glomerular filtration rate remain unaltered in normotensive insulin-dependent diabetic patients with microalbuminuria who had been smoking for several years.

Adult↗
PubMed1995

Unchanged incidence of diabetic nephropathy in IDDM patients.

Recently, a dramatic decline in the cumulative incidence of diabetic nephropathy (< 10% after 25 years of diabetes) has been reported in insulin-dependent diabetes mellitus (IDDM) patients diagnosed before the age of 15 years between 1961 and 1980. In a clinic-based study, we assessed recent trends in the incidence of diabetic nephropathy. All 356 patients in whom IDDM was diagnosed before the age of 41 years between 1965 and 1979, identified in 1984, were followed until 1991 or until death. All patients were Caucasians and resided in Copenhagen. The cumulative incidences (life-table method) of diabetic nephropathy (urinary albumin excretion > or = 300 mg/24 h in two out of three consecutive samples) after 15 years of diabetes and in 1991 were 18 +/- 4 and 35 +/- 5% (cumulative incidence +/- SE; onset of diabetes 1965-1969, n = 113), 20 +/- 4 and 35 +/- 5% (onset of diabetes 1970-1974, n = 130), and 16 +/- 5% (onset of diabetes 1975-1979, n = 113), respectively (NS at 15 years). The prevalence of persistent microalbuminuria (31-299 mg/24 h) at time of follow-up was 24% (95% confidence interval: 16-33) in the group with onset of diabetes in 1965-1969, 28% (20-36) with onset of diabetes in 1970-1974, and 19% (13-28) with onset of diabetes in 1975-1979 (NS). The mean +/- SE HbA1c measured yearly beginning in 1984 was higher in patients with nephropathy (9.4 +/- 0.1%) and persistent microalbuminuria (8.9 +/- 0.1%) than in patients with normoalbuminuria (8.5 +/- 0.1%; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Anticonvulsant, anxiolytic and discriminative effects of the AMPA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX).

The anticonvulsant effects of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), phencyclidine (PCP) and diazepam against audiogenic seizures in DBA/2 mice and against seizures induced by methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) in NMRI mice were compared. Motor impairment was assessed in a rotarod apparatus in DBA/2 as well as NMRI mice. At 30 min after i.p. administration, NBQX was as effective as PCP and diazepam in protecting against audiogenic seizures and had a therapeutic ratio slightly higher than diazepam's and 7-fold higher than PCP's. Whereas diazepam was fully effective, NBQX and PCP were both ineffective against seizures induced by DMCM 30 min after i.p. administration. The anticonvulsant potential and motor-impairing effects of NBQX were evaluated further by the i.p. and the i.v. routes at different time points after administration. At all pretreatment intervals, NBQX protected against audiogenic seizures more potently than it produced motor impairment. NBQX administered i.p. protected against DMCM-induced seizures when given 15 min but not 5 min before testing, whereas after i.v. administration NBQX produced anticonvulsant and motor-impairing effects in the same dose range. NBQX only slightly and non-dose-dependently attenuated the discriminative effects of pentylenetetrazole in rats, showing a limited anxiolytic potential. NBQX produced no PCP-like or morphine-like discriminative effects in rats, suggesting lack of PCP or opiate-like subjective effects. These data demonstrate that NBQX has anticonvulsant effects, has limited anxiolytic effects, and does not produce subjective effects of PCP or opiate type.

Acoustic Stimulation↗
PubMed1994

(S)-4-carboxy-3-hydroxyphenylglycine, an antagonist of metabotropic glutamate receptor (mGluR) 1a and an agonist of mGluR2, protects against audiogenic seizures in DBA/2 mice.

The in vivo anticonvulsant effects and in vitro metabotropic glutamate receptor selectivity of (S)-4-carboxy-3-hydroxy-phenylglycine [(S)-4C3HPG] were examined. Intracerebroventricular injection of (S)-4C3HPG dose-dependently antagonized audiogenic-induced clonic and tonic convulsions in DBA/2 mice with ED50 values of 76 and 110-nmol per mouse, respectively. (S)-4C3HPG dose-dependently inhibited the spontaneously evoked epileptic spikes in a cingulate cortex-corpus callosum slice preparation. (S)-4C3HPG displaced the binding of [3H]glutamate in membranes prepared from baby hamster kidney (BHK) cells expressing the metabotropic glutamate receptor mGluR1a with an EC50 of 5 +/- 1 microM. (S)-4C3HPG dose-dependently antagonized glutamate-stimulated phosphoinositide hydrolysis in BHK cells expressing mGluR1a with an IC50 of 15 +/- 3 microM. (S)-4C3HPG was, however, an agonist at mGluR2 with an EC50 of 21 +/- 4 microM for inhibition of forskolin-stimulated cyclic AMP formation in BHK cells expressing the mGluR2. (S)-4C3HPG had no effects at mGluR4a. These data suggest that the anticonvulsant action of (S)-4C3HPG is mediated by combined antagonism of mGluR1a and agonism of mGluR2. These results suggest the importance of mGluR1a and/or mGluR2 in the control of epileptic activity.

Acoustic Stimulation↗
PubMed1994

Isolation of Theileria parva (SAO Hill) and Theileria parva (West Kilimanjaro) and their cross-immunity with Theileria parva (Kasoba).

Two Theileria parva stocks were isolated from control cattle during East Cost fever (ECF) field immunization trials at SAO Hill and West Kilimanjaro in the southern and northern parts of Tanzania respectively. Both parasite stocks caused severe clinical ECF which required antitheilerial treatment for 3 of the 5 experimentally infected cattle. Cattle recovering from infection with the two T. parva stocks did not develop a fever and only 1 of 4 animals developed scanty schizont parasitosis for one day during a challenge with T. parva (Kasoba) from northern Malawi. In contrast, both control cattle developed fever and schizonts, and one required antitheilerial treatment to survive.

Animals↗
PubMed1993

The antiparkinsonian agent budipine is an N-methyl-D-aspartate antagonist.

Budipine (1-t-butyl-4,4-diphenylpiperidine) is a novel antiparkinsonian agent. Its clinical efficacy has been proven in double-blind placebo-controlled trials. The mechanism of action of budipine, however, is unknown. Budipine selectively increased the threshold of N-methyl-D-aspartate (NMDA)-induced seizures in mice. Similar to known specific NMDA antagonist, budipine depressed polysynaptic spinal reflexes in mice, but had no consistent effect on spinal monosynaptic reflexes. In receptor binding experiments, budipine displaced thienylcyclohexylpiperidyl-3,4-[3H]-(n) ([3H]-TCP) from its binding site with an IC50 of 36 microM suggesting that budopine acts as a non-competitive NMDA antagonist with moderate receptor affinity. It is concluded that the newly discovered NMDA antagonistic action of budipine is at least partly responsible for its antiparkinsonian activity. Our findings are additional evidence for the hypothesis that NMDA antagonists may be useful in the treatment of Parkinson's disease (PD).

Amino Acids↗
PubMed1993

Mixed solvent exposure and hearing impairment: an epidemiological study of 3284 men. The Copenhagen male study.

Animal experiments and human studies have indicated an effect on auditory functions from exposure to organic solvents. In this study the relationship between self-assessed hearing problems and occupational exposure to solvents was investigated in a cross-sectional design with 3284 participating men aged 53-74 years. Exposure to solvents for five years or more resulted in an adjusted relative risk (RR) for hearing impairment of 1.4 (95 per cent CI: 1.1-1.9) in men without occupational exposure to noise. Factors adjusted for were age, noise traumas, chronic middle ear infection and family history of hearing impairment. The prevalence of hearing impairment in men not exposed to organic solvents was 24 per cent and the attributable risk from solvent exposure was 9.6 per cent. Exposure for less than five years had no effect on hearing capacity. Occupational exposure to noise for five years or more had an effect twice that of solvents, RR: 1.9 (95 per cent CI: 1.7-2.1). In men exposed to both solvents and noise the effect of the latter dominated and no additional effect from solvents was found. A subsample of 51 men was examined with pure tone audiometry and 20 of 21 men who reported abnormal hearing also fulfilled an audiometric criterion for hearing impairment. In conclusion a damaging effect on hearing ability from long-term solvent exposure was found in the present study. The relative effect was moderate but with a high background frequency of hearing problems in the unexposed sample the absolute effect, ie attributable risk, was considerable and of both clinical and preventive importance.

Aged↗
PubMed1992

Inhibition of cisplatin-induced emesis in ferrets by the non-NMDA receptor antagonists NBQX and CNQX.

The excitatory amino acid (EAA) receptor antagonists, 2,3-dihydroxy-6-nitro-7-sulphamoylbenzo(f)quinoxaline (NBQX) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), which preferentially block non-N-methyl-D-aspartate (non-NMDA) subtypes of EAA receptors, effectively inhibit cisplatin-induced emesis in ferrets. A high dose of cisplatin (10 mg/kg i.v.) was used which induced emesis in all saline-treated control ferrets. At 10 mg/kg i.v., NBQX totally prevented cisplatin-induced emesis in 5 of 6 ferrets and CNQX totally prevented emesis in 3 of 5 ferrets. By comparison, each of the 5-HT3 inhibitors, zacopride and ondansetron, at 1.0 mg/kg i.v. (a dose considered in the high therapeutic range for controlling emesis by these compounds), totally prevented emesis in 2 of 5 ferrets. It is concluded that non-NMDA antagonists effectively inhibit cisplatin-induced emesis. They are potential antiemetic compounds, alone or in combination with 5-HT3 antagonists or other more conventional drugs of choice.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1992

Relief of experimental spasticity and anxiolytic/anticonvulsant actions of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline.

Spasticity is characterized by pathological overactivity in spinal stretch reflex circuits and may be associated with disturbances in excitatory amino acid-mediated transmission in the cord. A genetically determined syndrome of spasticity in the rat permits the quantitative evaluation of the antispastic effects of drugs by recording activity in the electromyogram (EMG) from a hind limb extensor muscle. In genetically spastic rats, systemic administration of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F) quinoxaline (NBQX), normalized pathologically increased EMG activity, whereas the AMPA agonist, alpha-amino-3-hydroxy-5-tertbutyl-4-isoxazolepropionate (ATPA), exacerbated the EMG measures of spasticity. The reflex mechanisms in the spinal cord can be studied in mice using EMG recordings from the tibial muscle (Hoffmann reflex) or from the plantar foot muscle (flexor reflex) after electrical stimulation of the tibial nerve. Systemic and i.t. administration of NBQX blocked Hoffmann reflexes in mice, leaving flexor reflexes unchanged. ATPA enhanced Hoffmann, and had no effect on flexor reflexes. The effects of NBQX on spinal reflexes were seen in doses which do not affect locomotor activity, but show anxiolytic and some antiepileptic activity in rodents. These data suggest that the design of novel muscle relaxant drugs acting at the AMPA subtype of glutamate receptors may be feasible.

Animals↗
PubMed1991

Protection against post-ischemic behavioral pathology by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) in the gerbil.

The neuroprotective effects of NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline) were assessed on hippocampal CA1 neuronal loss and locomotor hyperactivity following transient bilateral carotid artery occlusion (BCAO) in the gerbil. NBQX, a selective blocker of the AMPA glutamate receptor subtype, was injected 1 h after 5 or 10 min BCAO, or sham surgery. Both 5 and 10 min ischemia produced equivalent hyperactivity 3 days post ischemia and CA1 neuronal loss on Day 4, while activity was unchanged in the sham-operated group. NBQX protected from both hippocampal damage and post-ischemic hyperactivity. These results demonstrate that NBQX can protect from behavioral pathology induced by global cerebral ischemia.

Animals↗
PubMed1990

[Clinical environmental medicine. An examination of a case load from a 2-year project].

In a two year experimental project, 38 persons were referred to clinical examination at a clinic for occupational medicine. Admission was based upon suspicion of health damage caused by environmental factors outside the occupational setting. Twentyseven persons were suspected of indoor exposure with unspecified dust as the dominating factor. In the general environment, suspected exposure from polluted soil was the main reason for admission of 11 patients. In 22 cases, a causal relation between complaints and exposure to environmental factors was considered likely and recommendations to eliminate exposure or to effectuate further investigations of exposure were made. It is concluded that there is a need for an arrangement whereby patients can be examined by doctors experienced in assessing relations between exposure from environmental factors and disease. Since only few patients are expected, the examinations can be carried out in clinics for occupational medicine within existing resources.

Adolescent↗
PubMed1990

2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline: a neuroprotectant for cerebral ischemia.

2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) is an analog of the quinoxalinedione antagonists to the non-N-methyl-D-aspartate (non-NMDA) glutamate receptor. NBQX is a potent and selective inhibitor of binding to the quisqualate subtype of the glutamate receptor, with no activity at the NMDA and glycine sites. NBQX protects against global ischemia, even when administered 2 hours after an ischemic challenge.

Animals↗
PubMed1990

Chronic segmental spinal muscular atrophy of upper extremities in identical twins.

We present the 1st report of chronic segmental spinal muscular atrophy confined to the upper extremities in identical male twins. This occurrence in identical twins, together with reports of siblings and parent-child pairs of a disorder phenotypically similar to the more common sporadic form in the literature, suggests a genetic etiology in some cases.

Aged↗
PubMed1990

[High-dose inhaled beta-2 sympathomimetics in severe bronchial asthma].

We made the observations that in patients with severe bronchial asthma, the inhalative dose of beta-2 sympathomimetics that was required for optimal bronchial dilation revealed a large inter-individual scatter. In 21 patients, the inhalation of a maximum of 10 metered doses of salbutamol at intervals of five minutes each, led to a mean (SD) increase in the FEV 1.0 from 1.3 (0.6) 1 to 1.8 (0.7) 1. The maximum increase in the FEV 1.0 was achieved in 10 patients following the inhalation of 1 to 3 metered doses, and in 11 patients after 4 to 10 such doses. The individual requirement for inhaleable beta-2 agonists should therefore be taken into account when planning treatment.

Administration, Inhalation↗
PubMed1989

The flexural strength of repaired glass-ionomer cements.

The flexural strength of three glass-ionomer-type cements was measured by means of a four-point bend test. Specimens were tested at one hour and seven days after being mixed. The maleic copolymer materials showed similar strengths at one hour and seven days, while the water-based polyacrylic acid material showed a reduction in strength over the seven-day period. For assessment of the capacity of fresh glass ionomer to bond with old material, further half-length specimens of all materials were prepared and additions made at one hour and seven days. These specimens were tested at one hour and seven days after the addition. There was a considerable reduction in the strength of all specimens where additions had been made. The degree of reduction varied with the type of material. All fractures on the addition specimens occurred at the junction between the two sections.

Dental Bonding↗
PubMed1988

Quinoxalinediones: potent competitive non-NMDA glutamate receptor antagonists.

The N-methyl-D-aspartate (NMDA)-subtype of glutamate receptors has been well described as a result of the early appearance of NMDA antagonists, but no potent antagonist for the "non-NMDA" glutamate receptors has been available. Quinoxalinediones have now been found to be potent and competitive antagonists at non-NMDA glutamate receptors. These compounds will be useful in the determination of the structure-activity relations of quisqualate and kainate receptors and the role of such receptors in synaptic transmission in the mammalian brain.

6-Cyano-7-nitroquinoxaline-2,3-dione↗