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Biomedical subjects

J K Christensen

Publications and source records attributed to J K Christensen.

At least 19 recordsLinked to original sources
PubMed2001

[Ogilvie syndrome].

Ogilvie's syndrome is a rare condition with progressive dilatation of the proximal colon without mechanical obstruction. Untreated it can lead to coecal perforation, peritonitis and death. It develops in patients with medical or surgical complications, but can be idiopathic. Caesarean section is the most common preceding surgical procedure. An imbalance between the parasympathetic and the sympathetic innervation of the intestine is thought to be the cause. Trauma to the retroperitoneum, infections, bleeding and electrolyte disturbances, hormonal changes and medicamina are predisposing factors. The syndrome can result in perforation of the coecum as early as the third or fourth day. Therefore a diagnostic abdominal X-ray should not be delayed by the intermittent presence of flatus and stool which is characteristic for this pseudo-obstructive condition. Medical treatment with neostigmine may be successful, coloscopic decompression of the colon is effective as is placing a tube in or close to coecum. If laparotomy is necessary, coecostomy has lower mortality than ileo-coecal resection.

Colon↗
PubMed2001

Identification of amino acid residues in GluR1 responsible for ligand binding and desensitization.

Although GluR1(o) and GluR3(o) are homologous at the amino acid level, GluR3(o) desensitizes approximately threefold faster than GluR1(o). By creating chimeras of GluR1(o) and GluR3(o) and point amino acid exchanges in their S2 regions, two residues were identified to be critical for GluR1(o) desensitization: Y716 and the R/G RNA-edited site, R757. With creation of the double-point mutant (Y716F, R757G)GluR1(o), complete exchange of the desensitization rate of GluR1(o) to that of GluR3(o) was obtained. In addition, both the potency and affinity of the subtype-selective agonist bromohomoibotenic acid were exchanged by the Y716F mutation. A model is proposed of the AMPA receptor binding site whereby a hydrogen-bonding matrix of water molecules plays an important role in determining both ligand affinity and receptor desensitization properties. Residues Y716 in GluR1 and F728 in GluR3 differentially interact with this matrix to affect the binding affinity of some ligands, providing the possibility of developing subtype-selective compounds.

Amino Acid Substitution↗
PubMed2000

Agonist discrimination between AMPA receptor subtypes.

The lack of subtype-selective compounds for AMPA receptors (AMPA-R) led us to search for compounds with such selectivity. Homoibotenic acid analogues were investigated at recombinant GluR1o, GluR2o(R), GluR3o and GluR1o + 3o receptors expressed in Sf9 insect cells and affinities determined in [3H]AMPA radioligand binding experiments. (S)-4-bromohomoibotenic acid (BrHIBO) exhibited a 126-fold selectivity for GluR1o compared to GluR3o. Xenopus laevis oocytes were used to express functional homomeric and heteromeric recombinant AMPA-R and to determine BrHIBO potency (EC50) at these channels. (R,S)-BrHIBO exhibited a 37-fold selectivity range amongst the AMPA-R. It is hoped that BrHIBO can be used as a lead structure for the development of other subtype-selective compounds.

Animals↗
PubMed2000

Prevalence and prognostic significance of infection with TT virus in patients infected with human immunodeficiency virus.

No clear association between human disease and TT virus (TTV) has been documented. A possible pathogenic role of TTV was investigated in patients infected with human immunodeficiency virus (HIV). TTV serum concentrations were estimated in 185 HIV-infected patients by dilution polymerase chain reaction. Of these, 149 (76%) were TTV-positive, compared with 18 (7%) of 252 Danish blood donors (P<. 001). Of the HIV-infected patients who were TTV-positive, 72 (51%) had high TTV viremia (>/=5 times the highest concentration observed among blood donors, i.e., >/=3.5x105 TTV/mL of serum). High TTV viremia was associated with decreased survival (P<.001; relative hazard [RH], 2.0). There was a correlation between lower CD4+ T cell counts and higher TTV titers (P<.01). In a Cox regression model, CD4+ T cell count (P<.001), age (P<.001), HIV viral load (P<.001), beta2 microglobulin (P<.02), and high TTV viremia (P<.01; RH, 1.9) were independent predictors of survival. TTV is suspected to be an opportunistic pathogen with an independent influence on HIV progression.

AIDS-Related Opportunistic Infections↗
PubMed1995

Prolonged intrathecal chemotherapy replacing cranial irradiation in high-risk acute lymphatic leukaemia: long-term follow up with cerebral computed tomography scans and endocrinological studies.

UNLABELLED: Cranial irradiation in children with acute lymphatic leukaemia (ALL) decreases the risk of CNS relapse but is associated with serious long-term side-effects. We present the long-term outcome of 21 children with high-risk ALL who received prolonged intrathecal chemotherapy instead of the recommended cranial irradiation. Intrathecal triple therapy (methotrexate, hydrocortisone, and cytarabine) was administered every 2nd month throughout the maintenance phase. The average number of courses of intrathecal methotrexate was 8.7 and of triple 9.0. The 5-year event-free survival was 79%. No CNS relapses occurred. CT scan was performed at diagnosis, at cessation of therapy, and 3 years thereafter. No density abnormalities, pathological contrast enhancement, ventricular dilatation, or calcifications were found. One child showed cortical atrophy both at diagnosis and at cessation of therapy. There was a slight decrease in height SDS with time but no change in weight SDS. Delayed bone age was found in 5 children. No abnormalities of growth hormone, thyroid, adrenal, or gonadal function were observed. CONCLUSION: The study indicates that extended intrathecal chemotherapy in children with high-risk ALL may provide an effective protection from CNS relapses and is associated with a low risk of long-term side-effects.

Adolescent↗
PubMed1994

[Surgical treatment of dumping by the Lygidakis' method].

Dumping is a common adverse effect of gastrectomy and severe dumping is one of the most intractable conditions in gastroenterology. When medical treatment and diet are insufficient, different operative techniques have been tried, all with an unsatisfactory rate of success. The Lygidakis technique for operative treatment of postgastrectomy-dumping is presented, and results from operations on four patients presented. The results obtained are promising, and Lygidakis operation may be considered as an important alternative to wellknown operative techniques when medical treatment or diet is without effect on severe dumping.

Adult↗
PubMed1992

[Stress fractures].

The authors present stress fracture (fatigue fracture). Theories about the cause, the underlying mechanism, etiology, pathology, localisation, diagnoses and treatment are discussed, and two case histories are mentioned. Suitable precautions are recommended for runners. The authors would like to emphasize the importance of further investigations including technetium scintigraphic, in cases where stress fracture is suspected.

Adult↗
PubMed1992

Radiographic contrast media and release of neutrophil specific proteins in vitro and after intravenous injection.

The neutrophil granulocytes contain granules in which different proteins are present. When activated the neutrophils degranulate and thereby release some of these proteins to the surroundings. Some of these proteins are specific for this type of cell, e.g., lactoferrin and elastase. To investigate the influence of contrast media (CM) on this release, blood was incubated with diatrizoate, ioxaglate, iohexol, iodixanol, hyperosmolar saline, and hyperosmolar mannitol at different concentrations, and the amount of the neutrophil specific proteins lactoferrin and elastase were measured. Decreasing protein concentrations were observed for increased medium concentrations, suggesting that the degranulation process of the neutrophils was inhibited by the CM. The protein concentrations were lowest after incubation with the two ionic media diatrizoate and ioxaglate. Significantly decreased values of plasma lactoferrin were observed one min after i.v. injection of iohexol or ioxaglate in 82 patients undergoing urography. There was no significant difference between the two CM.

Contrast Media↗
PubMed1991

Dose-effect relationship of disulfiram in human volunteers. I: Clinical studies.

The aim of this study was to investigate the relation between Antabus dosage and the disulfiram-alcohol reaction (DAR) after ethanol challenge. Fifty-two healthy volunteers, 29 men and 23 women, aged 20-61 years, were treated with increasing doses of Antabuse (1, 100, 200, 300 mg) for 14 days each. At the end of each 14 days the volunteers were challenged with 0.15 g ethanol/kg body weight. Blood pressure, pulse rate, respiration rate, and symptoms such as flushing, heat sensation, nausea, vomiting, palpitations, breathlessness, and headache were monitored for the next 50 min. The volunteers left the study when they had experienced a valid DAR. A valid DAR, which was principally defined on the basis of the patients' feeling of discomfort, but for safety reasons also on the basis of unacceptable circulatory changes, was reached in 21 out of 52 volunteers after 100 mg Antabuse, in 27 after 200 mg, and in 4 after 300 mg. Most of them left the study after flushing and circulatory changes, but did not feel ill enough to be convinced that they should abstain from drinking. Ten volunteers with weak subjective symptoms, but with a valid DAR, were therefore rechallenged after the next increased dose and experienced a somewhat stronger reaction. We conclude that a daily dose of 200 mg Antabuse brings about a substantial reaction in volunteers in the presence of alcohol. The possible need for a 300 mg dose of Antabuse to prevent a patient from drinking was discussed.

Adult↗
PubMed1991

Dose-effect relationship of disulfiram in human volunteers. II: A study of the relation between the disulfiram-alcohol reaction and plasma concentrations of acetaldehyde, diethyldithiocarbamic acid methyl ester, and erythrocyte aldehyde dehydrogenase activity.

The study was designed to elucidate the basic pharmacological and biochemical effects of the disulfiram dose (Antabus) provoking disulfiram-alcohol reaction (DAR) in 52 human volunteers after ethanol challenge. Disulfiram was given daily in increasing doses (1, 100, 200, and 300 mg) in successive 14 day periods, with ethanol challenge at the end of each period, until a DAR was achieved. Irrespective of dose (except the 1 mg dose), the DAR was always accompanied by almost complete inactivation (about 97%) of aldehyde dehydrogenase (ALDH) activity in erythrocytes, plasma concentrations of diethyldithiocarbamic acid methyl ester (Me-DDC) in the range of 8-472 nmol/l and accumulated plasma concentrations of acetaldehyde in the range of 7-197 mumol/l. In four of the volunteers, the cardiovascular effects of the DAR were recorded as a decrease in diastolic blood pressure (14-47 mmHg) and an increase in pulse rate (9-40 beats/min.), accompanied by a two- to fourfold increase in the plasma concentrations of adrenaline and noradrenaline. The enzyme kinetics of ALDH in erythrocytes were regularly analysed in eight volunteers during DSF intake. In addition to the expected decrease in oxidizing capacity, the Km values were also impaired, which suggests that the inhibitor is implicated in an active site directed reaction.

Acetaldehyde↗
PubMed1988

Severity of illness and outcome of treatment in alcoholic patients in the intensive care unit.

To study whether critically ill alcoholics were more sick and had a worse outcome than other patients treated in the intensive care unit, data were collected during the initial 24 h on 216 consecutive patients admitted to an intensive care unit. Twentysix patients (12%) met the criteria for alcohol abuse. The patients' chronic health 6 months prior to admission and the extent of physiological derangement (Acute Physiology Score and Chronic Health Evaluation (APACHE] were recorded just as the type and amount of treatment (Therapeutic Intervention Scoring System (TISS]. Alcoholics were found to be significantly more sick and had a higher mortality (50% compared to 26%) than other critically ill patients. However, when analyzing the TISS points, no difference was found between the two groups. All survivors were, every third month up to 1 year after admission, asked to fill in a questionnaire indicating their level of activity. No differences were found between the two groups 1 year after admission, but the alcoholics had lost more time due to death. It is concluded that studies with larger number of patients will reveal whether alcoholics constitute a special category of patients with a different prognosis than other ICU patients.

Alcoholism↗
PubMed1987

Suriclone and diazepam in the treatment of neurotic anxiety. A double-blind cross-over trial.

Suriclone is a new anxiolytic drug belonging to the family of cyclopyrrolones. Although chemically entirely different from the benzodiazepines, it acts as a benzodiazepine agonist with very high affinity for the benzodiazepine receptors. In the present cross-over study, 33 out-patients with a diagnosis of neurotic anxiety were treated with suriclone (mean dose 2 mg/day) and diazepam (25 mg/day) in two 6-week periods. Both drugs had a significant anxiolytic effect, but diazepam appeared to have a better effect within the first 2 weeks of treatment, while no significant difference was seen after treatment, while no significant difference was seen after treatment for 6 weeks. Suriclone and diazepam had a different side effect profile: suriclone produced mainly dizziness, while diazepam caused sedation. This may reflect the fact that suriclone and benzodiazepines bind to distinct sites or different allosteric conformations of the benzodiazepine receptors.

Adult↗