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Biomedical subjects

B Wanscher

Publications and source records attributed to B Wanscher.

At least 19 recordsLinked to original sources

Nitric oxide synthase expression and enzymatic activity in multiple sclerosis.

We used post-mortem magnetic resonance imaging (MRI) guidance to obtain paired biopsies from the brains of four patients with clinical definite multiple sclerosis (MS). Samples were analyzed for the immunoreactivity (IR) of the three nitric oxide (NO) synthase isoforms [inducible, neuronal and endothelial nitric oxide synthase (NOS)], and enzymatic NO synthase activity. MRI guided biopsies documented more active plaques than macroscopic examination, and histological examination revealed further lesions. Inducible NOS (iNOS) was the dominant IR isoform, while reactive astrocytes were the dominant iNOS expressing cells in active lesions. NOS IR expressing cells were widely distributed in plaques, in white and gray matter that appeared normal macroscopically, and on MR. Endothelial NOS (eNOS) was highly expressed in intraparenchymal vascular endothelial cells of MS patients. A control group matched for age and sex showed no such changes. Our data support the hypothesis that NO is a pathogenic factor in MS, and that NOS IR is strongly expressed in brain regions appearing normal by MRI.

Adult↗

Efficacy and safety of short-term itraconazole in tinea pedis: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Treatment of plantar or moccasin-type tinea pedis with conventional oral antifungal agents produces poor response rates. Itraconazole is a synthetic, broad-spectrum, orally active antifungal agent with pronounced antimycotic activity. OBJECTIVE: To confirm the efficacy and safety of short-term treatment with itraconazole for plantar or moccasin-type tinea pedis. METHODS: The study was a double-blind, randomized, placebo-controlled, multicenter trial. Seventy-two patients with tinea pedis (plantar or moccasin-type) were treated with itraconazole (200 mg twice daily) or placebo for 1 week with an 8-week treatment-free follow-up period. RESULTS: Thirty-six patients were randomized to each treatment group. The overall success rate (mycological cure and clinical response) at the end-point of follow-up was significantly higher in the itraconazole group than in the placebo group (53 vs. 3%; p <0. 001). Mycological cure (56 vs. 8%; p <0.001) and clinical response rates (75 vs. 11%; p <0.001) were significantly higher after itraconazole treatment compared with placebo treatment. During treatment, adverse events were recorded in 7 patients in the itraconazole group and 2 patients in the placebo group. Adverse events were noted in 3 patients in the placebo group during follow-up. No serious adverse events were reported in either group. CONCLUSIONS: Short-term treatment with itraconazole was significantly more effective than placebo in tinea pedis. The safety and tolerability profile or itraconazole was comparable with placebo.

Abdominal Pain↗

Intravenous immunoglobulin G reduces MRI activity in relapsing multiple sclerosis.

We wanted to assess whether intravenous immunoglobulin G (IVIG) decreases disease activity on MRI in relapsing MS. Previous trials of IVIG in relapsing-remitting MS demonstrated a reduction of acute relapses, but these studies did not include MRI. We treated 26 patients in a randomized, double-blind, crossover study of IVIG 1 g/kg daily or placebo on 2 consecutive days every month during two 6-month treatment periods. The primary end point was the number of gadolinium-enhancing lesions on monthly serial MRI. Secondary efficacy variables were the occurrence of exacerbations, clinical neurologic ratings, total MS lesion load on T2-weighted MRI, and multimodal evoked potentials. Eighteen patients completed the entire trial; eight patients did not. Twenty-one patients completed the first treatment period and at least two MRI examinations in the second treatment period and were included in the intention-to-treat analysis. On serial MRI, we observed fewer enhancing lesions per patient per scan during IVIG treatment (median, 0.4; range, 0 to 9.3) than during placebo treatment (median, 1.3; range, 0.2 to 25.7; p = 0.03). During IVIG treatment, 15 patients were exacerbation free compared with only 7 on placebo (p = 0.02). The total number of exacerbations in the IVIG period was 11 and in the placebo period, 19 (not significant). None of the remaining secondary efficacy measures were significantly different between the two treatment periods. The number of adverse events, in particular eczema, was significantly higher during IVIG therapy than during placebo treatment. These results suggest that IVIG treatment is beneficial to patients with relapsing MS.

Adolescent↗

A double-blind, cross-over trial of intravenous immunoglobulin G in multiple sclerosis: preliminary results.

We enrolled 25 patients with relapsing-remitting or relapsing progressive multiple sclerosis (MS) in a randomized placebo-controlled double-blind study of intravenous immunoglobulin G (IVIG). IVIG 1 g/kg daily for 2 days was administered every 4 weeks for 24 weeks. Seventeen patients completed the whole trial, whereas eight patients discontinued the trial; four during IVIG treatment and four on placebo. Of the 17 patients who completed the trial, 11 had no exacerbations during IVIG treatment compared with only six on placebo (P=O.05). The total number of exacerbations in the IVIG period was 11 and in the placebo period 15 (NS), and the number of severe exacerbations requiring treatment with intravenous methylprednisolone was four during treatment with IVIG and six on placebo (NS). The results suggest that IVIG treatment may be of benefit for prevention of exacerbations in patients with relapsing MS.

Adult↗

Plasma exchange combined with azathioprine in multiple sclerosis using serial gadolinium-enhanced MRI to monitor disease activity: a randomized single-masked cross-over pilot study.

We enrolled 11 patients with secondary progressive MS in a randomized single-masked cross-over study of plasma exchange (PE) in combination with azathioprine 2 mg/kg. PE was performed once a week for 4 weeks and thereafter every second week for 20 weeks (14 treatments). Eight patients completed the whole trial, and three patients discontinued the trial, two during the run-in period of azathioprine treatment and one at the introduction of PE. The primary efficacy variables were the number of gadolinium-enhancing lesions and the occurrence of new enhancing lesions on serial MRI performed every 3 weeks during the PE and the control period. Secondary efficacy variables were the total MS lesion load on T2-weighted MRI, multimodal evoked potentials, and clinical neurologic ratings. No significant differences were found regarding the number of enhancing lesions or occurrence of new enhancing lesions in the two periods. Although the total MS lesion load on MRI was significantly lower (p < 0.02) and central motor conduction times decreased significantly (p < 0.05) during PE, this small study did not provide sufficient evidence for a significant beneficial effect of PE or encourage a subsequent large randomized parallel group study.

Adult↗

[Magnetic resonance imaging of disseminated sclerosis].

Multiple sclerosis is a chronic demyelinating disease. Paraclinical examinations may contribute to the diagnosis of multiple sclerosis. Magnetic resonance imaging (MRI) has a very high sensitivity concerning multiple sclerosis, and has made it possible to visualize multiple sclerosis plaques in vivo, to follow each plaque over the course of time and in this way to obtain information about the pathogenesis. MRI has shown that the size of plaques may vary considerably, and that plaques are dynamic structures with the ability to change in size over few weeks. By using MRI and the contrast agent Gadolinium-DTPA, it is possible to distinguish a newly developed plaque from an older one. Therefore, MRI has become an important examination in therapeutic trials. Just now, MRI with Gadolinium-DTPA is being used to evaluate the efficacy of plasmapheresis and immunoglobulin treatment in a joint study between Rigshospitalet and Hvidovre Hospital.

Contrast Media↗

[New therapeutic possibilities for disseminated sclerosis?].

Multiple sclerosis is a demyelinating disease of unknown origin. Immunological processes are thought to be of pathophysiological importance. Immunosuppressive treatment has been tried with various drugs in order to influence the immunological process. Steroid hormones are able to reduce the duration of an acute attack, but have no influence on the long-term progression. Cyclophosphamide can reduce disease activity a little, but has severe side effects. Azathioprine may reduce the frequency of acute attacks and disease progression a little. Cyclosporine A in the treatment of multiple sclerosis is only effective in doses so high that the side effects are unacceptable. Plasmapheresis in combination with immunosuppressive treatment is shown to stabilize the disease in some experiments. Intravenous polyclonal immunoglobulin has shown promising results in the treatment of other immunologically based diseases, and is a potentially beneficial treatment in multiple sclerosis. At Rigshospitalet, ongoing clinical trials will evaluate the efficacy of plasmapheresis and polyclonal immunoglobulin.

Antineoplastic Agents↗

Increased somatostatin and enkephalin-like immunoreactivity in the rat hippocampus following hippocampal kindling.

As neuropeptides may play a role in the electrical kindling model of epileptogenesis, hippocampal somatostatin, Met-enkephalin and cholecystokinin were studied by immunocytochemistry in rats 24 h following full hippocampal kindling (three stage 5 seizures). As control animals we used sham-kindled rats, unoperated rats and rats subjected to a single electroshock-induced seizure. In addition, the distribution of septohippocampal, cholinergic fibers and hippocampal mossy fibers were studied by histochemistry. The important finding was that after kindling there was, as compared to unoperated control, (1) a marked increase of somatostatin immunoreactivity in cell bodies in the dentate hilus and their presumed projections area in the outer parts of the dentate molecular layer, and (2) a marked increase of Met-enkephalin immunoreactivity in hippocampal mossy fiber terminals. We found no evidence of aberrant sprouting of mossy fiber collaterals in the fascia dentata.

Acetylcholinesterase↗

Grafts of fetal locus coeruleus neurons in rat amygdala-piriform cortex suppress seizure development in hippocampal kindling.

Hippocampal kindling was investigated in rats with a 6-hydroxydopamine-induced lesion of the forebrain catecholamine system after implantation of neural tissue from the fetal locus coeruleus region either bilaterally into the amygdala-piriform cortex (i.e., distant to the kindling site) or unilaterally into the hippocampus (close to the kindling site). Lesioned animals with either sham grafts or control grafts consisting of fetal striatal tissue showed a kindling rate much faster than that of normal controls. In contrast, in rats with bilateral locus coeruleus grafts in the amygdala-piriform cortex (implanted at three sites) the development of seizures was similar to that of controls and significantly slower than that in lesioned animals with sham grafts. All these animals had bilateral surviving grafts with a mean of 125 noradrenergic cells per implantation site. In the animals with locus coeruleus grafts in the stimulated hippocampus the kindling rate did not differ from that in the lesioned animals with control grafts. Most of these animals had large surviving grafts and showed a dense noradrenergic reinnervation of the implanted hippocampus. The present findings indicate that grafting of fetal pontine tissue (rich in noradrenergic neurons) to a site distant to the stimulation focus, but important for the generalization and spread of seizures, can retard the development of seizures in hippocampal kindling. Together with the data of our previous report this study also indicates that noradrenergic reinnervation of both hippocampi is important for the seizure-suppressant action in hippocampal kindling of locus coeruleus grafts implanted in the hippocampus.

Amygdala↗

Effects of adrenalectomy on urea synthesis in rats.

The effect of depletion of glucocorticoids on the dynamics of hepatic amino-N conversion was examined 2 and 7 days after adrenalectomy in a total of 22 rats substituted by adrenaline. The capacity of urea synthesis was studied by infusion of alanine under steady state conditions with arterial concentrations of alanine between 7.3 and 11.6 mmol/l. The animals were nephrectomized and the capacity was calculated as accumulation of urea in total body water corrected for intestinal hydrolysis. Adrenalectomy reduced the capacity of urea synthesis to 55% of the capacity for control rats and reduced the alanine metabolic rate to 60%. In control rats the urea synthesis exceeded the alanine infusion by indicating an extrahepatic tissue release of amino acids. This difference disappeared after adrenalectomy. The body weight and food intake did not change during the study period. Thus lack of glucocorticoids influences the in vivo nitrogen economy both by decreasing the liver function as to conversion of amino-nitrogen and by decreasing release of tissue amino-nitrogen.

Adrenalectomy↗

Cromones in atopic dermatitis.

Three new cromones have been studied that are supposed to be better absorbed and to have a wider spectrum of anti-allergic activity than disodium cromoglycate. Pretreatment with i.d. injection of 10 microgram FPL 52758 significantly reduced the weal and flare reaction induced by specific antigen in 11 patients with atopic dermatitis. The weal and flare reaction was not reduced in the same patients when 1.5 mg of FPL 52758 was applied topically under occlusion for a 24-h period prior to challenge with antigen. The itch and slight pain caused by antigen injection was not experienced in the FPL 52758 pretreated areas. Preliminary clinical results were obtained with the cromone FPL 52757, but due to possible hepatotoxicity this trial was not completed. Another similar cromone without hepatotoxicity was used in a double blind within-patient study. Nine patients with mild to moderate atopic dermatitis were treated with FPL 57787 (5%) ointment and matching placebo ointment. No significant improvement was observed after 4 weeks of treatment with the cromone containing ointment.

Chromones↗

Prevalence of skin diseases in old age.

The prevalence of skin disorders was studied in an elderly population comprising 584 individuals. The mean age was 80 years (range 55-106). The prevalence of pityriasis of the scalp and asteatosis was high, 44.3% and 28.9%, respectively. Psoriasis vulgaris was found in 2.9%, vitiligo in 1.2%, and contact dermatitis in 3.8% of the group.

Aged↗

Oral zinc therapy in geriatric patients with selected skin manifestations and a low plasma zinc level.

A geriatric population comprising 585 inhabitants of an institution for the aged was studied. Twenty-six persons with a mean age of 82 years were selected because of skin manifestations suggestive of chronic zinc deficiency. In 10 of the patients a subnormal plasma zinc level was found. This hypozincaemic group underwent a 4 week trial with zinc sulphate tablets, 0.6 g daily. The therapy failed to alleviate the skin condition in any of the patients, thus indicating that the changes were not caused by zinc deficiency. In the hypozincaemic group, plasma albumin was subnormal in all patients and significantly lower than in the normozincaemic subjects. The correlation between plasma zinc and plasma albumin levels in all 34 patients studied was highly significant (rs = 0.69, p less than 0.001). As plasma albumin tends to fall to subnormal concentrations with age, this explains why plasma zinc may be low in the elderly without indicating a state of zinc deficiency. After 2 and 4 weeks' zinc therapy, the mean plasma zinc concentration of the hypozincaemic group rose significantly from 9.5 to 17.6 and 23.4 mumol/1. This increase is higher than the rise observed in younger patients receiving an identical zinc sulphate dosage.

Aged↗

Oral injury caused by fellatio.

A 34-year-old Caucasian woman is presented with a circular hemorrhagic lesion located on the soft palate and caused by fellatio. The lesion consisted of erythema, petechiae, dilated blood vessels and vesicles. It healed in a few days. No evidence of the major clinical alternatives such as thrombocytopenia, venereal disease, candida infection or pathomimia were found. Injuries due to fellatio must be considered as an etiological factor to hemorrhagic changes of the oral mucosa, and with a positive history, patients can be spared from other investigations.

Adult↗

[Diagnosis and therapy of the zinc deficiency syndrome during total parenteral feeding. Review with report of a case].

A 47-year-old man with ulcerative colitis developed severe zinc deficiency during longterm intravenous feeding. Early symptoms included seborrhoeic lesions in the face and scalp. Later on his general condition deteriorated, and erythema and bullae erupted in the fingers, together with an erosive area with a marked border in the perianeal and scrotal regions. The symptomatology was suggestive of zinc depletion syndrome, a recently recognised acrodermatitis-enteropathica-like disorder in patients receiving longterm total intravenous feeding. A significantly lowered serum zinc level and a prompt beneficial response to intravenous zinc therapy (20 mg Zn2+ daily for one week) substantiate the provisional clinical diagnosis. As zinc depletion is caused by a zinc free parenteral alimentation this serious complication should be avoided by adding zinc to the infusions. Serum zinc determinations should be carried out as a control of the prophylactic zinc supply. Possibly, zinc plays a role in the symptomatology of various disorders with skin and bowel symptoms.

Acrodermatitis↗