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Biomedical subjects

P Holm

Publications and source records attributed to P Holm.

At least 19 recordsLinked to original sources

Elevated uptake of low density lipoproteins by human lung cancer tissue in vivo.

In order to explore new treatment modalities for cancer, it is important to identify qualitative or quantitative differences in metabolic processes between normal and malignant cells. Previous in vitro and in vivo studies have shown that acute myelogenous leukemia cells have elevated receptor-mediated uptake of low density lipoproteins (LDL), compared to normal WBC. High receptor-mediated uptake of LDL by certain cancer cells in tissue culture and experimental tumors in animals in vivo has also been demonstrated. The present study was undertaken to compare the in vivo assimilation of LDL by human lung cancer tissue with that by surrounding lung tissue. Ten patients with newly diagnosed lung tumors, scheduled for surgery, received an i.v. injection of [14C]sucrose-labeled LDL. Following cellular uptake and degradation of the LDL particle, the radiolabeled sucrose moiety remains trapped in the lysosomal compartment, making this labeling technique useful for in vivo studies of tissue uptake of LDL. Radioactivity was determined in plasma and in tissue biopsies obtained at surgery 1-3 days after injection. The uptake of radioactivity in lung cancer tissue was elevated (1.5-3.0-fold), compared to surrounding tissue, in 7 of 9 patients with primary lung cancer. The most rapid preoperative disappearance of radioactivity from plasma was found in 2 patients with large tumors exhibiting high LDL uptake, relative to normal lung tissue. These findings support the hypothesis that the selectivity of cytotoxic agents can be enhanced also in nonhematological malignancies by administering the drugs incorporated in LDL particles.

Adult

Moclobemide and placebo in mild major depression: a double-blind randomized trial.

Sixty-eight patients participated in this double-blind randomized study with moclobemide versus placebo (35 allocated to moclobemide; 33 to placebo). In terms of mean HAMD total scores, improvement tended to be more pronounced in the moclobemide group at treatment end-point. Efficacy was judged to be 'very good' or 'good' in 50% of moclobemide-treated patients and in 27% of placebo-treated patients: in completers only, the difference was more marked (69% versus 33%; P less than 0.05 Mann-Whitney test). Tolerability was judged to be 'very good' or 'good' in 77% of moclobemide-treated patients and in 94% of placebo-treated patients. Adverse events were observed in 31% of patients in the moclobemide group and in 18% of patients in the placebo group.

Adult

Hemorrhagic infarct conversion in experimental stroke.

STUDY OBJECTIVE: This study investigated the relations between hemorrhagic infarction and occlusion, release, levels of glycemia, brain energy state, and lactate content after cerebrovascular occlusion. DESIGN: Prospective, controlled laboratory investigation. TYPE OF PARTICIPANTS: One hundred six pentobarbital-anesthetized cats. INTERVENTIONS: The middle cerebral artery was occluded with a Yasargil clip transorbitally either temporarily (0.5, four, and eight hours) or permanently. Normoglycemic and hyperglycemic animals were closely monitored for eight hours. Brain pathology was assessed after two weeks' survival or at the time of spontaneous animal death. Topographic brain metabolite studies were carried out after four hours of middle cerebral artery occlusion. MEASUREMENTS AND MAIN RESULTS: Morphometric quantitation of cerebral hemorrhage and infarction and fluorometric determinations of blood and brain tissue, glucose, glycogen, lactate, adenosine triphosphate, and phosphocreatine from 16 topographic brain sites were carried out. Twenty-one of 82 (25.6%) animals evaluated neuropathologically showed hemorrhagic infarcts. Occluding the artery in hyperglycemic animals caused fivefold more frequent and 25-fold more extensive hemorrhage into infarcts than in normoglycemic animals. Temporary occlusion with clip release after four hours in hyperglycemic animals caused the most extensive hemorrhage into infarcts. Most hemorrhages into infarcts (81%) took place in animals that died within a few hours after they experienced ischemia and that showed infarction and marked edema of the entire middle cerebral artery territory. Linear regression analyses demonstrated a close relation between hemorrhage into infarcts and near-total energy depletion (adenosine triphosphate, less than 0.3 microM/g; phosphocreatine, less than 0.5 microM/g) in brain sites that showed extremely high tissue lactate concentrations (more than 30 microM/g). The biochemical changes that correlated with hemorrhage into infarcts were more marked than those with infarcts without hemorrhage. CONCLUSION: Hyperglycemia and restoration of blood flow to ischemic territories were strong risk factors for hemorrhagic infarct conversion. Concomitant tissue metabolic changes suggest that marked tissue energy depletion accompanied by acidosis damages brain vessels and renders them penetrable for edema fluid and, ultimately, red blood cell extravasation.

Adenosine Triphosphate

Treatment of lichen planus with acitretin. A double-blind, placebo-controlled study in 65 patients.

Sixty-five patients with lichen planus were included in a multicenter trial of acitretin. At the end of an 8-week placebo-controlled, double-blind phase, a significantly higher number of patients treated with 30 mg/day acitretin (64%) showed remission or marked improvement compared with placebo (13%). Furthermore, during the subsequent 8-week open phase, 83% of previously placebo-treated patients responded favorably to acitretin therapy. Typical retinoid adverse reactions were present in all patients on active drug. Laboratory studies did not show any clinically significant changes. This study shows that acitretin is an effective and acceptable therapy for severe cases of lichen planus.

Acitretin

Moclobemide in depression: a randomized, multicentre trial against isocarboxazide and clomipramine emphasizing atypical depression.

Moclobemide was compared with isocarboxazide and clomipramine in patients with depression. A total of 167 outpatients were allocated to daily treatment with 300 mg moclobemide, 30 mg isocarboxazide or 150 mg clomipramine for 6 weeks. Moclobemide was slightly inferior to clomipramine, whereas isocarboxazide had an intermediate position. There was no interaction between treatment and atypical or nonatypical depression. Anticholinergic symptoms and orthostatic hypotension were most pronounced in the clomipramine group.

Adult

Bisection of bovine morulae and blastocysts from superovulated Danish dairy cows.

Sixtyfour compacted morulae and blastocysts were bisected with a microscalpel. The majority of the demi-embryos (n = 122) were reinserted into separate zona pellucidae (ZP) before non-surgical transfer to 113 synchronized recipients, as singles (n = 98) (DE-S) or in pairs (n = 30) (DE-P). Thirty non-manipulated embryos (E) were transferred during the same period and served as controls. Pregnancies were diagnosed by rectal palpation 4-7 weeks after transfer. The pregnancy rates for DE-S, DE-P and E were 32%, 53% and 40%, respectively (P greater than 0.05). A substantial number of abortions were recorded between 50 and 250 days of pregnancy among the recipients with DE-S. The fetal survival rate for DE-S was reduced to 21% and significantly lower (p less than 0.05) than the survival rates of DE-P (43%) and E (40%). The quality of DE and the presence of ZP did not significantly influence the results. No conclusive reasons for the fetal loss could be found but different possibilities are discussed.

Animals

Bromazepam in generalized anxiety. Randomized, multi-practice comparisons with both chlorprothixene and placebo.

Bromazepam was compared with placebo and with chlorprothixene in a randomized, double-blind group-comparative multicenter trial in general practice. Two hundred and forty-five patients with generalized anxiety disorder (DSM-III 1980) were treated for 2 weeks with two daily doses of bromazepam, 3 mg or chlorprothixene, 15 mg or placebo. Median reductions in Hamilton Anxiety rating were 12 (bromazepam), 10.3 (chlorprothixene) and 7.3 (placebo). The study revealed significant superiority of bromazepam over placebo (median differences 3.3, 95% confidence limits: 0.3 and 6.1) but not over chlorprothixene (median difference 1.4, 95% confidence limits -0.8 and +3.5). Significantly higher rates of tiredness, sedation and hypersomnia were found on bromazepam and chlorprothixene compared to placebo. Tolerance was rated as "at least good" in 85.6% on bromazepam, in 86% on chlorprothixene and in 87.8% on placebo. Neither previous psychopharmacological treatment nor presence of psychosocial stress were of perceptible influence. Bromazepam and chlorprothixene are both superior to placebo in generalized anxiety states treated in general practice, but spontaneous improvements/placebo effects are substantial.

Adolescent

Moclobemide and clomipramine in endogenous depression. A randomized clinical trial.

The purpose of this study was to compare moclobemide and clomipramine in endogenous depression according to the Newcastle II classification. Sixty-two patients were allocated to either 300 mg moclobemide or 150 mg clomipramine, both given in 3 daily doses. Improvements occurred over time but differences between treatments were never statistically significant. Dizziness, tremor and anticholinergic symptoms were significantly more frequent with clomipramine.

Adult

Moclobemide and clomipramine in reactive depression. A placebo-controlled randomized clinical trial.

The purpose of this study was to compare moclobemide and clomipramine in reactive depression according to the Newcastle II classification. Sixty patients were allocated to either 300 mg moclobemide, 150 mg clomipramine or placebo, all divided in 3 daily doses. Improvements occurred over time, but differences between treatments and compared with placebo were never statistically significant. Dizziness, tremor and anticholinergic symptoms were significantly more frequent with clomipramine than with moclobemide and placebo.

Adjustment Disorders

Domoprednate, a new nonhalogenated topical steroid: comparison to hydrocortisone butyrate.

Thirty-nine patients with mainly psoriasis vulgaris and atopic dermatitis were treated for 4 weeks with 0.1% domoprednate and hydrocortisone butyrate ointment according to a right-left, randomized design. Various assessments of efficacy only revealed marginal, but statistically insignificant differences. Patients' preferences for one of the two treatment favored domoprednate in 20 cases and hydrocortisone butyrate in 12 cases; 6 cases were ties (p greater than 0.2). The efficacy of domoprednate, a new, nonhalogenated topical steroid, is evidently at least of the same order as that of the hydrocortisone butyrate, and the tolerance of the two ointments is equally good.

Administration, Topical

A long-term randomised trial on tenoxicam and piroxicam in osteoarthritis of the hip or knee: a 24-month interim report focusing on the 12-24 month interval.

The long-acting antiphlogistics tenoxicam (Ro 12-0068, Tilcotil) and piroxicam in single daily oral doses of 20 mg are compared in a double-blind, group-comparative, randomised trial planned to last for five years. Results of 12 months' treatment of 108 patients with osteoarthritis of the hip or knee have been reported. This interim analysis focuses mainly on the 12 to 24 month interval. The clinical improvements obtained within the first 12 months persisted during the second year in the 55 patients remaining on treatment. After 24 months, 53 patients had been withdrawn prematurely, three-quarters because of inefficacy or intolerance. Only six patients were withdrawn between 12 and 24 months, three for lack of efficacy, two for side-effects and one for reasons unrelated to therapy. There was no difference between the treatment groups with regard to incidence, time or reason for withdrawal, and only small, insignificant differences in efficacy and tolerability. This trial shows that long-term treatment of osteoarthritis with tenoxicam and with piroxicam is beneficial. Once efficacy and tolerability have been established, maintenance of therapy is feasible.

Activities of Daily Living

Domoprednate (Stermonid), a topical D-homocorticosteroid, skin atrophy and telangiectasia. A double-blind, randomized comparison with hydrocortisone butyrate, betamethasone valerate, clobetasole propionate and placebo.

Five corticosteroid ointments and placebo were compared in 17 volunteers with regard to their influence on normal skin under occlusive conditions. Each volunteer had six simultaneous applications on the forearms and six on the back. The trial was double-blind and lasted 4 weeks. The ointments were placed in randomized order. The treatments were 0.1 and 0.03% domoprednate, 0.1% hydrocortisone butyrate, 0.1% betamethasone valerate, 0.05% clobetasole propionate and placebo. Skin thickness was measured on days 0, 7, 14, 21 and 28, transepidermal water loss on days 0, 14 and 28, while blood flow and telangiectasias were evaluated only on day 28 at termination of the trial. The skin thickness became significantly reduced on all corticosteroids, but not on placebo; 0.03% domoprednate, however, tended to have an intermediate position between placebo and the other ointments. The transepidermal water loss did not change. Rating of telangiectasia under stereomicroscope showed a significantly lower score after 0.03% domoprednate and placebo as compared to the other ointments. Assessment of telangiectasia by laser-Doppler flowmetry showed a similar tendency. It is concluded that 0.1% domoprednate is comparable to other topical corticosteroids with respect to atrophogeneity and formation of telangiectasia, but the 0.03% concentration seems to result in fewer side effects.

Administration, Topical

The treatment of psoriasis with 0.1% domoprednate (a D-homocorticosteroid) and 0.1% betamethasone valerate ointment. A double-blind, randomized trial.

In 85 patients with psoriasis vulgaris the efficacy and tolerance of domoprednate and betamethasone valerate were studied in a double-blind, randomized trial lasting 4 weeks. Complete or satisfactory remission was obtained in 36% in the domoprednate group and in 53% in the betamethasone group. This difference is not statistically significant (p greater than 0.10). 3 patients on each treatment experienced some local irritation. No laboratory abnormalities were found during the study.

Adolescent

[Continuous cervix measurement (author's transl)].

A new technique has been devised for high-continuity recording of cervical dilatation during labour. The measuring principle is based on Hall's effect. The sensor is superior to conventional methods by its smaller dimensions and weight and the possibility of on-line processing. The new method is used in conjunction with cardiotocography to test the action of medicaments upon cervical behaviour and labour.

Cervix Uteri

Dopaminergic agonist Ro 8-4650 in Parkinson's disease. I. Patients treated with dopa.

An isoquinoline derivative Ro 8-4650 (rac-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-7-methoxy-2-methylisoquinoline hydrochloride) with dopaminergic properties was studied in a randomized crossover trial. The group studied comprised 37 patients with idiopathic parkinsonism and persistent symptoms, despite levodopa treatment. Median Webster rating before allocation was 11.5. The trial drug did not differ significantly from placebo as regards effect and involuntary movements. It led to more frequent minor side effects.

Clinical Trials as Topic

Long-term treatment with sulphamethoxazole/trimethoprim (Bactrim) and nitrofurantoin in chronic urinary tract infections. A controlled clinical trial.

In a controlled clinical trial based on 30 geriatric patients with recurrent urinary tract infection, 12 out of 17 patients fulfilled a 12-month treatment with sulphamethoxazole/trimethoprim (Bactrim) with continuous sterile urine compared to 1 out of 13 patients treated with nitrofurantoin (p less than 0.05). There was a slight but statistically significant increase in serum creatinine during treatment for 12 months in the sulphamethoxazole/trimethoprim group, but this probably does not reflect any deterioration in kidney function. The remaining laboratory values showed no significant changes whatsoever.

Aged

The retinoic acid derivative Ro 11-1430 in Acne vulgaris. A controlled multicenter trial against retinoic acid.

In a double-blind controlled multicenter trial consisting of 257 patients with acne vulgaris an 8-week topical treatment with the retinoic acid derivative Ro 11-1430 (0.1% lotion) was compared with vitamin A acid (0.05% lotion) and the lotion alone (placebo). In reducing the number of comedones vitamin A acid was superior to Ro 11-1430, which was significantly better than placebo. The reduction in number of papules and pustules was not statistically significant on either treatment. Local side effects, i.e. erythema, desquamation, burning and pruritus occurred more frequently and were more severe on vitamin A acid than on Ro 11-1430 and placebo which did not differ. No correlation was found between incidence and severity of local reactions and therapeutic effect.

Acne Vulgaris