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H C Klein

Publications and source records attributed to H C Klein.

17 recordsLinked to original sources

[18F]FHPG positron emission tomography for detection of herpes simplex virus (HSV) in experimental HSV encephalitis.

Herpes simplex virus type 1 (HSV-1) is one of the most common causes of sporadic encephalitis. The initial clinical course of HSV encephalitis (HSE) is highly variable, and the infection may be rapidly fatal. For effective treatment with antiviral medication, an early diagnosis of HSE is crucial. Subtle brain infections with HSV may be causally related to neuropsychiatric disorders such as Alzheimer's dementia. We investigated the feasibility of a noninvasive positron emission tomography (PET) imaging technique using [(18)F]FHPG as a tracer for the detection of HSE. For this purpose, rats received HSV-1 (infected group) or phosphate-buffered saline (control group) by intranasal application, and dynamic PET scans were acquired. In addition, the distribution of tracer accumulation in specific brain areas was studied with phosphor storage imaging. The PET images revealed that the overall brain uptake of [(18)F]FHPG was significantly higher for the infected group than for control animals. Phosphor storage images showed an enhanced accumulation of [(18)F]FHPG in regions known to be affected after intranasal infection with HSV. High-performance liquid chromatography metabolite analysis showed phosphorylated metabolites of [(18)F]FHPG in infected brains, proving that the increased [(18)F]FHPG uptake in infected brains was due to HSV thymidine kinase-mediated trapping. Freeze lesion experiments showed that damage to the blood-brain barrier could in principle induce elevated [(18)F]FHPG uptake, but this nonspecific tracer uptake could easily be discriminated from HSE-derived uptake by differences in the tracer kinetics. Our results show that [(18)F]FHPG PET is a promising tool for the detection of HSV encephalitis.

Animals↗

Plasma cholecystokinin in obese patients before and after jejunoileal bypass with 3:1 or 1:3 jejunoileal ratio--no role in the increased risk of gallstone formation.

BACKGROUND AND AIM: Jejunoileal bypass surgery for obesity increases the risk of gallstone formation, and, contrary to expectations, the incidence is greater in patients with a long as compared to a short ileum left in continuity. Impaired gallbladder motility due to reduced cholecystokinin (CCK) stimulation could be an explanation. The aim of this study was to investigate the CCK levels in such patients. SETTING: The randomized trial of bypass surgery named The Danish Obesity Project. DESIGN AND METHODS: We compared plasma levels of CCK in obese patients at three, nine or 15 months after jejunoileal bypass surgery with either a 1:3 jejunoileal ratio (n = 14) or a 3:1 ratio (n = 15), and in unoperated obese patients (n = 7). Plasma CCK levels were determined during fasting and during 150 min following ingestion of a liquid test meal. RESULTS: There were no significant changes over time following surgery. Basal CCK levels were significantly increased after surgery, and significantly higher in those with a 3:1 than in those with a 1:3 jejunoileal ratio. The postprandial AUC (mean +/- SEM) was 935 +/- 71 pM x min in the 3:1 ratio group and 891 +/- 100 pM x min in the 1:3 ratio group. This difference was not significant, but both bypass groups were significantly higher than the unoperated group (515 +/- 79 pM x min). The integrated increase in plasma CCK above basal level showed a similar pattern, but the difference between the unoperated and the bypass groups was insignificant. CONCLUSION: Postoperative changes in plasma CCK levels neither explain the increased risk of gallstone formation after bypass surgery nor the higher incidence with a long compared to a short ileum left in continuity in the bypass.

Cholecystokinin↗

Prediction of specific damage or infarction from the measurement of tissue impedance following repetitive brain ischaemia in the rat.

The development of irreversible brain damage during repetitive periods of hypoxia and normoxia was studied in anaesthetized rats with unilateral occlusion of the carotid artery (modified Levine model). Rats were exposed to 10 min hypoxia and normoxia until severe damage developed. As indices of damage, whole striatal tissue impedance (reflecting cellular water uptake), sodium/potassium contents (due to exchange with blood). Evans Blue staining (blood-brain barrier [BBB] integrity) and silver staining (increased in irreversibly damaged neurons) were used. A substantial decrease in blood pressure was observed during the hypoxic periods possibly producing severe ischaemia. Irreversibly increased impedance, massive changes in silver staining, accumulation of whole tissue Na and loss of K occurred only after a minimum of two periods of hypoxia, but there was no disruption of the BBB. Microscopic examination of tissue sections revealed that cell death was selective with reversible impedance changes, but became massive and non-specific after irreversible increase of the impedance. The development of brain infarcts could, however, not be predicted from measurements of physiological parameters in the blood. We suggest that the development of cerebral infarction during repetitive periods of hypoxia may serve as a model for the development of brain damage in a variety of clinical conditions. Furthermore, the present model allows the screening of potential therapeutic measuring of the prevention and treatment of both infarction and selective cell death.

Animals↗

Rat striatal cation shifts reflecting hypoxic-ischemic damage can be predicted by on-line impedance measurements.

We investigated the earliest time at which irreversible damage takes place after hypoxia-ischemia in the Levine preparation of rats. In 60 rats anesthetized with chloral hydrate and maintained at one of three body temperatures, we unilaterally ligated the left common carotid artery and placed electrodes in the striatum to measure impedance (reflecting the extracellular space) during hypoxia, recovery, and/or cardiac arrest. We measured blood gases and pH at regular intervals during hypoxia in 47 rats and assessed blood-brain barrier function with Evans blue and tissue damage using Na+:K+ ratios. Shortly after hypoxia, impedance normalized in 24 rats without brain damage (normal Na+:K+ ratios, 4 hours of recovery). Sustained elevation of striatal impedance during recovery in six rats was related to an elevated Na+:K+ ratio and a disrupted blood-brain barrier. Damage was not obviously related to blood gases, pH, or the net reduction of the extracellular space during hypoxia. Hypothermia in 17 rats prevented impedance changes, and no striatal damage was found. Thus, irreversible brain damage very likely occurs during or very shortly after hypoxia. Persistent reduction of the extracellular space indicates tissue damage and can be used to monitor potential in vivo therapeutic measures.

Animals↗

Increases in striatal and hippocampal impedance and extracellular levels of amino acids by cardiac arrest in freely moving rats.

The time course of changes in the tissue impedance and the levels of extracellular transmitter and non-transmitter amino acids was studied in the striatum and hippocampus of the unanesthetized rat after cardiac arrest. Electrodes were implanted for the continuous measurement of tissue impedance so that a measure of the volume of extracellular space was provided. Alternatively, bilateral dialysis probes were used for monitoring levels of extracellular amino acids in subsequent 30-s samples using an automated precolumn derivatization technique for reversed-phase HPLC analysis and fluorimetric detection. The impedance started to rise approximately 1.2 min following cardiac arrest, increased rapidly during the first 5 min, and increased almost linearly thereafter. After 15 min, a decrease of approximately 50% in the extracellular space was calculated. The impedance rose more steeply in the striatum than in the hippocampus. The extracellular levels of taurine, which increased greater than 300% within 5 min after cardiac arrest, most closely resembled the time course of the change in impedance. Glutamate and aspartate levels did not increase until 5 min after circulatory arrest, and at 15 min they had risen to a level of 465 and 265% for the striatum and 298 and 140% for the hippocampus of the resting release, respectively. The release of gamma-aminobutyric acid (GABA) was multiphasic and did not resemble that of any of the other--putative--transmitter amino acids. Fifteen minutes after cardiac arrest, the levels of GABA were 617 and 774% of the resting release in the striatum and hippocampus, respectively. Glycine and alanine efflux substantially increased (232 and 151% in striatum and 141 and 154% in hippocampus, respectively) 15 min postmortem, whereas the glutamine level was slightly increased and levels of asparagine, histidine, threonine, ethanolamine, serine, arginine, and tyrosine were inconsistently higher in the two brain regions. At this time, the extracellular levels of glutamate, GABA, and aspartate were only slightly lower, as expected from the tissue levels and from levels of the other amino acids, an observation indicating that all the amino acids may diffuse through postmortem brain tissue to a nearly similar extent.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗

Prospective study of malabsorption induced risk of gall stone formation in relation to fall in plasma cholesterol.

The relationship between cholesterol in plasma and risk of gall stone formation was investigated in 210 obese patients who underwent jejunoileal bypass surgery and were free of gall stone disease at the time. Among 185, successfully reexamined on average 19 months after surgery, 26 (14%) developed gall stones. The fall in plasma cholesterol after surgery exhibited a U-shaped relation to risk of gall stone formation with a minimum risk around the average fall (2.6 mmol/l). This was confirmed by multivariate logistic regression analysis (p less than 0.01) taking into account other possible determinants. The relation was not significantly dependent on weight loss or ratio between jejunum and ileum left in function. The study suggests that malabsorption induced fall in plasma cholesterol is related to risk of gall stone formation by two oppositely working mechanisms, one enhancing and one reducing the risk.

Adult↗

Teach us so we may see.

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Education, Medical, Undergraduate↗

Serum levels of T4, T3, reverse T3, 3,3'-diiodothyronine and 3',5'-diiodothyronine in obesity, before and after jejuno-ileal bypass.

Serum T4, 3,5,3'triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3, rT3), 3,3'-diiodothyronine (3,3'-T2), 3',5'-diiodothyronine (3',5'-T2) and thyrotrophin (TSH) levels were studied in nineteen obese patients before and 6, 12, and 18, months after a jejuno-ileal bypass. Before surgery, the obese patients had increased serum T3 levels compared with a group of lean, matched controls (median: 1.94 nmol/l v. 1.44 nmol/l, P less than 0.01). Serum T3 decreased to normal (1.64 nmol/l) 18 months after surgery. A slight decrease was also observed in serum 3,3'-T2 levels, whereas progressive reductions in serum concentrations of rT3 and 3',5'T2 occurred. Eighteen months postoperatively the serum levels of rT3 and 3',5'-T2 had decreased from 0.676 nmol/l to 0.430 nmol/l (P less than 0.02) and 55.2 pmol/l to 40.0 pmol/l (P less than 0.01), respectively, and the values at 18 months were also reduced compared with the control group [0.722 nmol rT3/1 (P less than 0.01), 51.4 pmol 3',5'-T2/1 (P less than 0.01)]. concomitant with the decrease in serum level of the iodothyronines, serum TSH concentrations increased from 0 Micro U/ml to 0.9 microu/ml (P less than 0.01).

Adult↗

Correlation between exocrine pancreatic secretion and serum concentration of human pancreatic polypeptide in chronic pancreatitis.

Concentrations of human pancreatic polypeptide (HPP) in serum were measured in the fasting state and after a meal in 19 control subjects and 24 patients with chronic pancreatitis (CP). The severity of CP was characterized on the basis of the duodenal lipase concentration after a test meal (Lundh test). Basal and postprandial HPP concentrations were significantly (p less than 0.01) decreased in severe and moderate chronic pancreatitis and in diabetes secondary to pancreatitis. There was only a weak correlation (r = 0.44; p less than 0.05) between exocrine secretion and delta HPP in CP. Fifty-eight percent of patients with CP had serum concentrations of HPP within the normal range, limiting the value of serum HPP measurement in the diagnosis of CP.

Adult↗

Risk of gallstone formation after jejunoileal bypass increases more with a 1:3 than with a 3:1 jejunoileal ratio.

The rate of gallstone formation after jejunoileal bypass and the influence on the rate of the jejunoileal ratio of the functioning segment were assessed in 265 obese patients without stones in the gallbladder. After on the average 20.1 months of observation 231 patients were adequately examined for gallstones, which had developed in 2 (4%) out of 46 unoperated patients, in 9 (9%) out of 100 with a 3:1 jejunoileal ratio, and in 17 (20%) out of 85 with a 1:3 jejunoileal ratio of the functioning segment of the bypass. This result suggests that the association of ileal dysfunction and gallstone formation depends on the length of the functioning jejunum, which, according to previous studies, may reduce bile lithogenicity by stimulating bile salt synthesis.

Adult↗

Plasma enteroglucagon after jejunoileal bypass with 3:1 or 1:3 jejunoileal ratio.

Enteroglucagon concentration in peripheral blood was determined before and after a test meal in 24 morbidly obese patients. Eighteen had jejunoileal bypass, 6 with a 3:1 and 12 with a 1:3 jejunoileal ratio of the functioning segment, and 6 were unoperated. All three groups exhibited an increment of enteroglucagon concentration after the meal. Both the fasting values and the postprandial integrated increments were higher in operated patients than in unoperated patients and higher after 1:3 bypass than after 3:1 bypass. The findings agree with the hypothesis that enteroglucagon secretion is stimulated by exposure of the lower bowel to upper-bowel content, and that the effect of enteroglucagon is, as seen after bypass operation, stimulation of growth and reduction of motility of the intestine.

Adult↗

Routine telescopic laryngoscopy.

Routine laryngoscopy can be performed easily and quickly utilizing a right-angle telescope with a specially designed holder. In 1,000 consecutive laryngoscopies done on patients without laryngeal symptoms, abnormalities were found in 173 patients (17.3 percent). Among the abnormalities was an asymptomatic carcinoma which, thanks to early detection, was successfully treated by radiation.

Aged↗