PubMed Health⌕ Search

Biomedical subjects

F S Larsen

Publications and source records attributed to F S Larsen.

At least 55 records · Page 3Linked to original sources
PubMed1997

Oral terbinafine in toenail dermatophytosis. A double-blind, placebo-controlled multicenter study with 12 months' follow-up.

The treatment of onychomycosis has previously often been protracted and unsuccessful. Terbinafine has been shown to be effective in short-term regimens. In this double-blind, placebo-controlled study, 148 patients with toenail dermatophytosis were randomized to treatment with either 250 mg terbinafine daily or placebo for 3 months. An additional treatment was given for 3 months to patients whose infection had not responded. The patients were followed clinically and mycologically through 12 months. After 3 months 82% of the terbinafine-treated group, versus 5% of the placebo group, showed significant improvement, i.e. negative culture and growth of unaffected nail more than 2 mm (p = < 0.0001). After 12 months clinical and mycological cure was seen in 40% of the patients treated with terbinafine for 3 or 6 months, while 67-81% were clinically cured, but with positive microscopy. Side-effects occurred in 13.5% of the terbinafine group, versus 5.4% of the placebo group, and were mild. 250 mg terbinafine daily for 3 months was significantly more effective than placebo. The efficacy did not appear to improve with additional treatment for 3 months.

Administration, Oral↗
PubMed1996

Preservation of cerebral oxidative metabolism in fulminant hepatic failure: an autoregulation study.

Under normal conditions cerebral blood flow (CBF) is regulated to secure oxidative brain metabolism, but in patients with fulminant hepatic failure (FHF), insufficient CBF has been suggested to precede cerebral edema and intracranial hypertension. In order to determine if insufficient CBF and hypoxia are present in patients with FHF we increased the mean arterial pressure and measured cerebral metabolism. In six patients with FHF CBF determined by 133Xenon injection technique, transcranial Doppler mean flow velocity in the middle cerebral artery (Vmean) and cerebral metabolism were determined, before and after an increase in mean arterial pressure by norepinephrine infusion. Mean arterial pressure was measured in a radial artery, and blood samples from the radial artery and internal jugular vein allowed calculation of the cerebral arteriovenous oxygen (AVDO2), -glucose (AVDgl), and -lactate (AVDlac) differences. Cerebral metabolic rates (CMRO2,-gl,-lac) were calculated as AVDO2,-gl,-lac times CBF. Mean arterial pressure was raised from 70 (54-105) to 111 (93-128) mm Hg during intravenous infusion of norepinephrine. CBF increased from 34 (12-55) to 47 (27-81) mL . 100g-1. min-1 (p < 0.05) and Vmean from 53 (42-60) to 67 (61-79) cm.s-1 (p < 0.05), whereas CMRO2 (1.4 (0.9-2.4) mL . 100g-1 . min-1), CMRgl (11 (4.8-20) mumol 100g-1 . min-1), and CMRlac (3.2 (0-8.9) mumol . 100g-1 . min-1) remained unchanged. Our finding indicates that cerebral oxidative metabolism is preserved in patients with FHF. Cerebral autoregulation is absent, however, and neuroprotective critical care is suggested to be guided by internal jugular vein oxygen saturation to secure appropriate cerebral oxygenation.

Adolescent↗
PubMed1996

Dissociated cerebral vasoparalysis in acute liver failure. A hypothesis of gradual cerebral hyperaemia.

BACKGROUND/AIMS: Normally, cerebral blood flow responds to changes in the arterial carbon dioxide tension (PaCO2) but not to changes in mean arterial pressure, commonly referred to as the cerebral CO2-reactivity and autoregulation. In patients with fulminant hepatic failure and in the rat with thioacetamide-induced liver failure, autoregulation is absent, presumably due to cerebral vasoparalysis. Since also CO2-reactivity may then be compromised, it was studied in patients with fulminant hepatic failure and rats with thioacetamide-induced liver failure. METHODS: In ten patients (median age 32 (range 20-48) years)) and in ten age-matched volunteers, cerebral perfusion was elevated by transcranial Doppler assessed mean flow velocity (V(mean)) in the middle cerebral artery during hypo- and hyper-capnia. In six rats with liver failure and in six control rats, cerebral blood flow was measured repeatedly by the intracarotid 133 Xenon injection technique. RESULTS: In the patients and volunteers, PaCO2 was lowered from 33 (23-44) to 28 (23-39) mmHg by hypocapnia and raised to 40 (34-48) mmHg by hypercapnia or 5% CO2 inhalation. During hypocapnia, the CO2-reactivity did not differ significantly between patients and volunteers, 4.0 (1.1-7.4) vs. 3.0 (1.7-5.0)% mmHg(-1), while it was reduced during hypercapnia in the patients, 2.2 (1.8-5.2) vs. 4.6 (3.0-8.0)% mmHg(-1) (p < 0.05). In the rats, PaCO2 was reduced from 39 (37-40) to 30 (29-31) mmHg and then raised to 51 (41-55) mmHg. During hypocapnia, CO2-reactivity was similar in rats with liver failure and in control rats, 2.3 vs 2.7% mmhg(21), respectively. In all rats with liver failure CO2-reactivity was abolished during hypercapnia, while it was 1.5% mmHg(-1) in the control rats (p < 0.01). CONCLUSIONS: The finding that cerebral CO2 reactivity is reduced in hypercapnia, while it is preserved in hypocapnia, suggests that gradual dilation of the cerebral resistance vessels develops in fulminant hepatic failure and connects previous morphological studies with changes in the regulation of cerebral blood flow, i.e. impaired cerebral autoregulation and blunted CO2-reactivity.

Acute Disease↗
PubMed1996

Validation of transcranial near-infrared spectroscopy for evaluation of cerebral blood flow autoregulation.

The aim of the study was to evaluate a new noninvasive transcranial near-infrared spectroscopy (TNIRS) technique for determination of the lower limit of cerebral blood flow (CBF) autoregulation by comparing this technique with the standard cerebral arteriovenous oxygen saturation difference (AVDo2) method. In eight healthy volunteers, mean arterial blood pressure was increased by infusion of angiotensin and decreased by the combination of lower-body negative pressure and labetalol. For each 5-mm Hg change in mean arterial pressure, blood was sampled from the bulb of the internal jugular vein and a radial artery, and simultaneously, the oxygen saturation of hemoglobin in the brain was measured with an INVOS 3100 Cerebral Oximeter (Somanetics). The lower limit of autoregulation was then calculated by a computer using (a) AVDo2 and (b) the difference between arterial oxygen saturation and the saturation determined with the cerebral oximeter (ACDo2). The median lower limit of autoregulation determined by the two methods was 73 and 78.5 mm Hg, respectively (p > 0.05). A statistically significant correlation between relative CBF (percentage of baseline) determined with the two methods was found below the lower limit of autoregulation (1/AVDo2 = 12 + 0.8 x 1/ACDo2; r = 0.55; p < 0.001). For all the 98 pairs of saturations registered, the correlation was 0.37 (p < 0.001), the mean difference was 16%, and the limits of agreement were -2.2 and 33.8%. We conclude that the cerebral oximeter might be useful in evaluation of the lower limit of cerebral autoregulation. This method, however, is of no value for estimation of levels of global cerebral oxygen saturation.

Adult↗
PubMed1996

Cerebral blood flow, oxygen metabolism and transcranial Doppler sonography during high-volume plasmapheresis in fulminant hepatic failure.

OBJECTIVE: The effect of high-volume plasmapheresis on hepatic encephalopathy, cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) was investigated in patients with fulminant hepatic failure (FHF). METHODS: Twelve consecutive patients (8 women, 4 men, median age 34 years (range 19-51), were studied before and after high-volume plasmapheresis with 10-16 litres fresh frozen plasma, while PaCO2 and body temperature were maintained at 30 (23-34) mmHg and 37.6 degrees C (36.6-38.4), respectively. Blood samples from the internal jugular vein and a radial artery allowed calculation of the cerebral arteriovenous oxygen difference (AVDO2) and oxygen extraction (AVDO2 divided by arterial oxygen content). CBF was determined by a xenon-133 clearance method in eight patients and CMRO2 calculated as AVDO2 times CBF. Cerebral perfusion pressure (CPP) was determined as the difference between mean arterial and subdural pressures in eight patients. RESULTS: High-volume plasmapheresis was initiated 22 (6-168) h after the development of hepatic encephalopathy and 11 patients had grade 4 encephalopathy. Following high-volume plasmapheresis the grade of encephalopathy improved in four patients. The CBF increased from a median of 31 (16-86) to 45 (18-97) ml/100 g/min and as oxygen extraction remained unchanged (32 (9-41) vs. 29 (7-39)%), CMRO2 increased from 1.24 (0.96-1.82) to 1.86 (1.00-2.07) ml/100 g/min (P < 0.05). The CPP increased from 62 (19-76) to 92 (50-105) mmHg (P < 0.01), whereas the intracranial pressure remained unchanged (19 (3-45) vs. 11 (5-33) mmHg). No statistical difference was found between the relative changes in the above parameters in survivors compared to non-survivors. CONCLUSION: Although the clinical status did not improve in all patients, both CBF and CMRO2 increased after high-volume plasmapheresis. The alleviation of brain oxygen metabolism by high-volume plasmapheresis may reflect partial removal of neuroinhibitory plasma factors.

Adult↗
PubMed1996

Atopic dermatitis may be linked to whether a child is first- or second-born and/or the age of the mother.

Five hundred and thirty families with at least 1 child who had been referred to a dermatologist with atopic dermatitis were interviewed in an effort to determine whether factors such as the age of the mother when a child is born and/or birth rank can contribute to the development of atopic dermatitis. The families interviewed had a total of 1,084 children, or an average of 2 children per family. Sixty per cent of the children with atopic dermatitis were under 5 years of age. Ninety-one per cent of them had developed the disease before the age of 3; those most severely affected had developed the disease during the first year of life. In families with 2 children, but only 1 child with atopic dermatitis, the odds ratio for the second child to develop atopic dermatitis was 1.379 (0.025 < p < 0.05). The average maternal age was 24.8 to 25.2 years when giving birth to the first child and 28 years when giving birth to the second child, irrespective of the status of the child. Thus, atopic dermatitis can be related to birth rank or to the age of the mother.

Adult↗
PubMed1995

[Paracetamol poisoning at a department of hepatology].

In this retrospective study we evaluated the frequency of complications in 108 patients with acetaminophen poisoning admitted to the Department of Hepatology, Rigshospitalet, Copenhagen from 1.10.1990-30.9.1993. Twenty-five patients (23%) developed hepatic encephalopathy grade II-IV, with a survival rate of 44%. In patients who developed grade IV encephalopathy the median time from intoxication to INR > 3.7 was 60 hours. At a median of only five hours later grade II encephalopathy was present, and grade IV at a median of a further 20 hours later. Ninety-three patients were re-evaluated according to the nomogram indicated by Prescott (6). If the initial position was in the "very severe" area the risk of developing encephalopathy was 34% (20-51%), if not the risk was 6% (1-16%). Serum creatinine above 200 microM at admission indicated a risk of hepatic encephalopathy of 64% (35-87%). INR > 1.54 was associated with a 35% risk of hepatic encephalopathy. Patients in the "very severe" area should be referred to a unit where liver transplantation is possible, even if other factors known to indicate poor prognosis are not present.

Acetaminophen↗
PubMed1995

[Poisonings due to analgesics during a period of 14 years in Denmark--a registry study of the period 1979-1992].

The study describes consumption of and poisoning by analgesic drugs in Denmark during the period 1979-1992. During this period, fatal poisonings from analgesics almost doubled to 200 deaths per year (40% of all drug related deaths in Denmark). The annual consumption of opioids increased at the beginning of the period, but during 1985-1992 it was relatively constant at 20 million defined daily doses (DDD) and associated with 600 hospital admissions and 150-170 deaths due to poisoning per year. Within the opioid group dextropropoxyphene consumption and poisonings decreased following a National Board of Health initiative in 1985-1987. As for the weak analgesics, consisting mainly of paracetamol or salicylates, the total consumption increased gradually and reached 145 million DDD in 1992, corresponding to 160 tablets per inhabitant per year. This consumption was associated with approximately 750 hospital admissions and 40 deaths due to poisoning. As judged from the mortality per dose the weak analgesics are 20-30 times safer than the opioids.

Analgesics↗
PubMed1995

[Fulminant liver failure before and after introduction of liver transplantation at Rikshospitalet].

The impact of liver transplantation on the survival in fulminant hepatic failure was evaluated in a retrospective study including 87 patients admitted to Rigshospitalet over a three and a half year period before and a three and a half year period after the Danish liver transplantation programme was started. The number of admissions increased by 178% in the second period. Fifty-two percent of the patients had acetaminophen induced liver failure, which over the last seven years has become the most common cause of severe acute liver disease in Denmark. In about half of the patients high volume plasmapheresis was used as liver-assist either alone or in combination with liver transplantation. Three patients in grade 4 hepatic coma (one with Hepatitis B, two with acetaminophen intoxication) were withdrawn from the waiting list for emergency liver transplantation after high volume plasmapheresis due to recovery. In patients with an estimated survival chance of less than 5-10% liver transplantation was performed with a survival rate of 60%. The survival rate for the non-liver transplanted patients was 49% in the same period compared to 30% in the three and a half year period before liver transplantation started.

Acetaminophen↗
PubMed1995

Isolation by anion-exchange of immunologically and enzymatically active human islet glutamic acid decarboxylase 65 overexpressed in Sf9 insect cells.

The enzyme L-glutamic acid decarboxylase is a major autoantigen of the beta cell. Autoantibodies against this enzyme are observed before the onset of insulin-dependent diabetes mellitus (IDDM) in man and may be of predictive value. There is evidence that this enzyme is involved in the development of autoimmune diabetes in animals. In order to facilitate the investigation of the role of L-glutamine acid decarboxylase in IDDM, we expressed the 65 kDa isoform of human islet L-glutamic acid decarboxylase in insect cells using a baculovirus-based vector. The material was expressed at high levels (up to 50 mg/l of cells). Partially purified metabolically labelled L-glutamic acid decarboxylase bound to immunoglobulins in the sera from 20 of 49 subjects with newly-diagnosed IDDM. The enzyme was isolated in high yields (up to 26 mg/l cell culture) with fully maintained enzymatic activity by either ion-exchange chromatography or immunoaffinity chromatography. Purified L-glutamic acid decarboxylase inhibited the binding of radioactive L-glutamic acid decarboxylase, prepared by in vitro translation of mRNA, to immunoglobulins in the sera of subjects with IDDM. Recombinant human islet L-glutamic acid decarboxylase, isolated from Sf9 cells, is a suitable material for the large scale investigation of the utility of this enzyme in the prediction and prevention of autoimmune diabetes.

Adolescent↗
PubMed1995

Functional loss of cerebral blood flow autoregulation in patients with fulminant hepatic failure.

In management of patients with fulminant hepatic failure, it is recommended that mean arterial pressure should be raised if cerebral perfusion pressure is lower than 50 mmHg, but the influence of such therapy on cerebral blood flow is unknown. We examined cerebral blood flow autoregulation in seven consecutive patients with fulminant hepatic failure during treatment of imminent insufficient cerebral perfusion pressure. Cerebral perfusion was evaluated by transcranial Doppler assessed mean flow velocity in the middle cerebral artery and by the arterio-venous difference for oxygen. Intracranial pressure was recorded by a subdural transducer and cerebral perfusion pressure calculated as the difference between mean arterial pressure and intracranial pressure. After 20 (range 10 to 43) min, mean arterial pressure was raised from 74 (43-80) to 94 (76-114) mmHg by i.v. noradrenaline, cerebral perfusion pressure increased from 49 (26-75) to 82 (50-108) mmHg (p < 0.01) as the intracranial pressure remained unchanged at 26 (3-35) mmHg. The mean flow veolocity increased from 68 (30-134) to 108 (48-168) cm s-1 and the arterio-venous difference for oxygen by 46 (10-82)% (p < 0.05). Both mean flow velocity (r = 0.63) and arterio-venous difference for oxygen (r = 0.71) were correlated to mean arterial pressure (p < 0.001), and a lower blood pressure limit of autoregulation could not be identified in any of the patients. These data suggest that the cerebral blood flow is not autoregulated in patients with fulminant hepatic failure and therefore cerebral blood flow should be "clamped" within the normal physiologic range by manipulation of arterial blood pressure in order to avoid cerebral hypoxia and/or hypertensive induced cerebral oedema.

Acute Disease↗
PubMed1995

Comparison of sandwich enzyme-linked immunoadsorbent assay and radioimmunoassay for determination of exogenous glucagon-like peptide-1(7-36)amide in plasma.

A sensitive sandwich enzyme-linked immunoadsorbent assay (ELISA) for determination of exogenous glucagon-like peptide-1(7-36)amide (GLP-1(7-36)amide) in plasma samples from pharmacokinetic studies is described. The assay employs an N-terminally directed antibody and a C-terminally directed antibody. The ELISA has a working range from 10 to 500 pmol l-1, and can be applied to plasma samples from humans, dogs, pigs, minipigs, cats, rabbits, and rats. The assay was compared to a validated radioimmunoassay (RIA), employing an antibody directed against the mid-region of GLP-1. After s.c. administration of GLP-1(7-36)amide, the plasma immunoreactivity of GLP-1 (P-GLP-1-IR) measured by ELISA was markedly lower than P-GLP-1-IR measured by RIA. After HPLC fractionation of plasma samples with subsequent RIA and ELISA analyses of the fractions, this difference was shown to be due to cross reaction with biologically inactive fragments of GLP-1(7-36)amide in the RIA but not in the ELISA.

Amino Acid Sequence↗
PubMed1995

Effect of labetalol on cerebral blood flow, oxygen metabolism and autoregulation in healthy humans.

We have studied the effects of labetalol on cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO2) in eight healthy volunteers. CBF was measured by single photon emission computerized tomography before and during infusion of labetalol. CMRO2 was calculated as CBF x cerebral arteriovenous oxygen content difference (CaO2-CvO2). CBF autoregulation was tested during infusion of labetalol by changing arterial pressure and estimating relative changes in global CBF from changes in (CaO2-CvO2). CBF before and during infusion of labetalol was 67 and 65 ml/100 g min-1, respectively (P > 0.05). CMRO2 was 2.9 and 2.8 ml/100 g min-1, respectively (P > 0.05). CBF autoregulation was preserved in all subjects. The lower limit of CBF autoregulation was 88 mm Hg (94% of baseline mean arterial pressure). We conclude that labetalol did not influence global or regional CBF, or CMRO2, and CBF autoregulation was preserved.

Adult↗
PubMed1995

Cerebral perfusion during human liver transplantation.

During transplantation of the liver cerebral perfusion was monitored by transcranial Doppler determined middle cerebral artery mean flow velocity (Vmean) and pulsatility index (PI) in six fulminant hepatic failure patients and 11 patients with chronic liver disease. In both groups of patients Vmean, PI and central haemodynamic variables were recorded during (1) the last preanhepatic hour; (2) the anhepatic phase; (3) the first 15 min of reperfusion; and (4) for the following 45 min of reperfusion. No significant differences were detected between the two groups of patients with respect to changes of variables with time. The Vmean (40 +/- 13 cm s-1 [mean +/- SD]), thoracic electrical impedance (TI) (30 +/- 7 Ohm), heart rate (97 +/- 19 beats min-1), mean arterial pressure (84 +/- 9 mmHg) and arterial carbon dioxide tension (PaCO2, 4.5 +/- 0.4 kPa) remained stable in the anhepatic phase, while cardiac output (CO, 7.6 +/- 2.7 to 5.4 +/- 1.41 min-1), stroke volume (SV, 79 +/- 26 to 56 +/- 15 ml) and PI (1.2 +/- 0.3 to 0.9 +/- 0.2) decreased (P < 0.05). During reperfusion, CO (9.9 +/- 4.01 min-1), SV (105 +/- 40 ml), PaCO2 (5.5 +/- 0.6 kPa), Vmean (57 +/- 17 cm s-1) and PI (1.2 +/- 0.2) became elevated. Taken together, during the anhepatic phase of the liver transplantation a maintained central blood volume as indicated by the constant TI served for a stable blood pressure and in turn cerebral perfusion, whereas revascularization of the graft increased cerebral perfusion concomitant with an elevated carbon dioxide tension.

Adult↗
PubMed1995

Impaired activity and gene expression of hexokinase II in muscle from non-insulin-dependent diabetes mellitus patients.

After entering the muscle cell, glucose is immediately and irreversibly phosphorylated to glucose-6-phosphate by hexokinases (HK) I and II. Previous studies in rodents have shown that HKII may be the dominant HK in skeletal muscle. Reduced insulin-stimulated glucose uptake and reduced glucose-6-phosphate concentrations in muscle have been found in non-insulin-dependent diabetes mellitus (NIDDM) patients when examined during a hyperglycemic hyperinsulinemic clamp. These findings [correction of finding] are consistent with a defect in glucose transport and/or phosphorylation. In the present study comprising 29 NIDDM patients and 25 matched controls, we tested the hypothesis that HKII activity and gene expression are impaired in vastus lateralis muscle of NIDDM patients when examined in the fasting state. HKII activity in a supernatant of muscle extract accounted for 28 +/- 5% in NIDDM patients and 40 +/- 5% in controls (P = 0.08) of total muscle HK activity when measured at a glucose media of 0.11 mmol/liter and 31 +/- 4 and 47 +/- 7% (P = 0.02) when measured at 0.11 mmol/liter of glucose. HKII mRNA, HKII immunoreactive protein level, and HKII activity were significantly decreased in NIDDM patients (P < 0.0001, P = 0.03, and P = 0.02, respectively) together with significantly decreased glycogen synthase mRNA level and total glycogen synthase activity (P = 0.02 and P = 0.02, respectively). In the entire study population HKII activity estimated at 0.11 and 11.0 mM glucose was inversely correlated with fasting plasma glucose concentrations (r = -0.45, P = 0.004; r = -0.54, P < 0.0001, respectively) and fasting plasma nonesterified fatty acid concentrations (r = -0.46, P = 0.003; r = -0.37, P = 0.02, respectively). In conclusion, NIDDM patients are characterized by a reduced activity and a reduced gene expression of HKII in muscle which may be secondary to the metabolic peturbations. HKII contributes with about one-third of total HK activity in a supernatant of human vastus lateralis muscle.

Adult↗