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Biomedical subjects

M Grönroos

Publications and source records attributed to M Grönroos.

At least 19 recordsLinked to original sources

Altered skin sensitivity in chronic itch: role of peripheral and central mechanisms.

Nodular prurigo (NP) is a chronic skin disease causing severe itch of unknown origin in restricted skin areas surrounded by healthy skin areas. In the present investigation we studied cutaneous sensibility in five NP-patients and in five control subjects. Pain thresholds were determined with short argon laser pulses using two different sizes of stimulus surface (diameters 2 and 4 mm), tactile threshold with calibrated monofilaments and skin blood flow with a laser Doppler flowmeter. We also studied the effect of prolonged capsaicin treatment which should predominantly impair the function of nociceptive C-fibers. In both the itching and healthy skin areas the pain thresholds were lower in NP-patients than in healthy control subjects. Before capsaicin, an increase in stimulus area produced an equal decrease in pain threshold in all subjects. Following prolonged capsaicin treatment the pain threshold obtained with a large but not a small stimulus surface was elevated to control levels in NP-patients. Tactile thresholds in NP-patients were lower than in control subjects, and this abnormality was reversed by capsaicin. The basal skin blood flow level was more labile (fluctuating) in itching skin areas than in healthy skin areas of NP-patients. Capsaicin reduced blood flow fluctuation in the itching area. A lowered pain threshold not only in the itching area but also in the healthy skin area of NP-patients suggests that central convergence of itch and pain may contribute to increased pain sensitivity in chronic itch. Capsaicin-reversible abnormal fluctuation of the blood flow in the itching skin area might be explained by abnormal spontaneous activity of nociceptive peripheral nerve fibers and a consequent release of vasoactive agents from their terminals (axon reflex). The decreased tactile threshold and the elevation of it by capsaicin indicates that also the mechanisms underlying tactile sensibility are changed in chronic itch patients.

Adult

Influence of selective nerve fiber blocks on argon laser-induced thermal pain in the human skin.

Influence of selective nerve fiber blocks on cutaneous pain induced by short argon laser pulses was studied in healthy humans. The minimal energy per surface area needed to produce a pain sensation was lower with a larger stimulus surface indicating spatial summation. Both compression of the peripheral nerve innervating the stimulus site (A-fiber block) and prolonged topical treatment of the stimulus site with 1% capsaicin (a predominant block of nociceptive C-fibers) produced an elevation of the pain threshold. Prolonged capsaicin treatment produced significantly higher pain thresholds than the compression block. Magnitude of the pain threshold elevation induced by nerve blocks varied depending on the area of the stimulus surface. Especially following prolonged capsaicin treatment, pain threshold elevations tended to be smaller with the larger area of the stimulus surface suggesting an enhanced spatial summation effect. Tactile thresholds were significantly elevated only by the compression block. The results indicate that nociceptive C-fibers have a significant contribution to the threshold sensation of pain induced by argon laser. Moreover, following impairment of function in nociceptive C-fibers, the spatial summation of argon laser-induced pain tends to be enhanced.

Adult

Endometrial fluid accumulation in asymptomatic postmenopausal women.

Postmenopausal endometrial fluid accumulation was considered in the past to be related to cancer of the genital organs. Our purpose was to evaluate its prevalence, and its association with cervical stricture, use of hormone replacement therapy and endometrial pathology. A group of 1074 asymptomatic postmenopausal women aged 57-61 (mean 59) years was examined by transvaginal sonography with color Doppler imaging. Women who had an endometrial fluid accumulation underwent endometrial biopsy. Statistical analysis was mainly based on analysis of variance. Endometrial fluid accumulation was found in 134 women (12%). Women using only estrogen as hormone replacement therapy had a relative risk of 3.5 of endometrial fluid accumulation. In 12 women (9%), a cervical stricture precluded endometrial sampling. Six abnormal histopathological samples were found (5%): two endometrial polyps, one cystic hyperplasia, two adenomatous hyperplasias but only one adenocarcinoma. One further patient with endometrial cancer was registered by the Finnish Cancer Registry 2.5 years later in a woman who had refused endometrial sampling. Endometrial fluid accumulation is quite a common finding on transvaginal sonography among asymptomatic postmenopausal women and the process may be multifactorial. Cervical stricture is not the most important etiological factor. The use of estrogen replacement therapy increases the risk of endometrial fluid accumulation; however, it is rarely a sign of malignancy.

Analysis of Variance

Evaluation of ovarian findings in asymptomatic postmenopausal women with color Doppler ultrasound.

BACKGROUND: To evaluate the prevalence and significance of abnormal ovarian findings in asymptomatic postmenopausal women, screening for ovarian cancer with color Doppler ultrasound was performed. METHODS: One thousand three hundred sixty-four asymptomatic women aged 56-61 years (mean, 59 years) were examined by color Doppler sonography. Ninety-six percent of the examinations were transvaginal and 4% transabdominal. The criteria for abnormality were an ovarian volume 8 cm3 or greater, nonuniform echogenicity, and/or pulsatility index (PI) of the ovarian artery or tumor vessel, if present, 1.0 or less. Repeat sonograms were performed 1-3 months later on all patients with abnormal findings, and exploratory laparotomy was performed if a malignant tumor was suspected. RESULTS: Abnormal ovarian findings were detected in 160 women (12%). At the time of repeat sonogram there were 28 persisting abnormalities (2%). At that time, the ovary was regarded as normal if it still contained a small clear cyst with an unchanged greatest dimension of less than 20 mm. Three women had a low PI value but all had also abnormal ovarian sonographic morphology. Two ultrasound-guided cyst punctures were performed and three patients had surgery; one benign serous cyst, one benign serous cystadenoma, and one serous cystadenoma of borderline malignancy were detected. The remaining abnormal findings disappeared or remained unchanged during a minimum follow-up of 2 years. One case of Stage IA ovarian cancer has been reported 2 years after a negative screening and one abdominal carcinomatosis 2 1/2 years after a negative screening result. CONCLUSIONS: There is a high frequency of small ovarian cysts in asymptomatic postmenopausal women. A large percentage of these cysts regress spontaneously or remain unchanged. Transvaginal color Doppler ultrasound is an effective method for detecting these lesions. Color Doppler does not increase substantially the number of operations for benign reasons. However, as a primary screening modality, the conventional sonography seems to be quite sufficient.

Female

Effect of cocaine on sexual behaviour in male stumptail macaques (Macaca arctoides).

The effect of cocaine (0.01-1.0 mg/kg) on sexual behaviour was studied in four male stumptail macaques (Macaca arctoides). Following drug-saline control administration, the behaviour of the male monkey with a female was observed for 30 min in two different behavioural conditions; in one of the conditions the baseline sexual activity was low, and in the other it was high (partial or complete separation of the male and the female between the sessions, respectively). The reversal of the cocaine-induced effects was attempted by haloperidol (0.003-0.01 mg/kg), a dopamine-2-receptor antagonist. Cocaine (0.1-1.0 mg/kg) produced a highly significant dose-dependent suppression in the number of ejaculations. The cocaine-induced suppression of ejaculatory behaviour was completely reversed by haloperidol. Haloperidol at the dose range used did not in itself influence ejaculatory behaviour. The effect of cocaine on grooming, nonejaculatory mounting, aggression, or perineal investigations did not reach statistical significance. The possibility that cocaine at very low doses (0.01-0.1 mg/kg) might increase sexual activity was excluded in the behavioural condition with a low basal sexual activity. The results indicate that cocaine dose-dependently suppresses ejaculatory behaviour as a result of dopamine-2-receptor-mediated mechanisms. The cocaine-induced suppression of ejaculatory behaviour might be explained by the strong rewarding effect of cocaine alone.

Animals

An attempt to attenuate experimental pain in humans by dextromethorphan, an NMDA receptor antagonist.

Dextromethorphan (100 mg, orally), an NMDA receptor antagonist, did not significantly attenuate pain intensity or unpleasantness induced by experimental ischemia or by topical capsaicin in healthy human subjects, nor did it increase the threshold for heat pain or mechanical pain. A dose of 200 mg produced marked side effects. Thus, systemically administered dextromethorphan does not attenuate pain at clinically applicable doses in humans.

Adult

Transdermal estrogen for female stress urinary incontinence in postmenopause.

OBJECTIVE: To evaluate the effect of transdermal estrogen for stress urinary incontinence in postmenopause. STUDY DESIGN: An open within patient, dose-finding study with transdermal 17-beta-estradiol combined with cyclic medroxyprogesterone acetate was conducted over 9 months in 21 patients (mean age 57.3 years) suffering from urodynamically verified mild to moderate stress incontinence without detrusor instability. RESULTS: Subjective improvement was noted in 16 out of 21 patients (76%). The dose level of 50 micrograms was better tolerated than 100 micrograms and sufficient enough to achieve continence. CONCLUSION: Transdermal estrogen therapy plays an adjuvant role in conservative therapy for mild to moderate stress urinary incontinence in postmenopausal women.

Administration, Cutaneous

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Adult

Capsaicin-induced central facilitation of a sympathetic vasoconstrictor response to painful stimulation in humans.

The effect of capsaicin, a compound selectively activating nociceptive primary afferent fibers, on a centrally mediated autonomic (sympathetic) vasoconstriction response to painful peripheral stimulation was studied in healthy human volunteers. Capsaicin (1%) was applied topically to the dorsal forearm and the threshold for eliciting a vasoconstriction response in the contralateral forefinger to painful electrical or thermal stimulation of the forearm skin adjacent to or remote from the capsaicin-treated region was determined with Laser Doppler flowmetry. Capsaicin produced a significant decrease of the threshold for the vasoconstriction response to painful electrical stimulation of the area of central allodynia; i.e., the skin area located adjacent to the capsaicin-treated region in which a light touch evoked an unpleasant sensation. Capsaicin did not change the threshold for the vasoconstriction response to painful heat stimuli applied to the area of central allodynia or to painful electric stimulation applied outside the borders of the allodynic area. Heart rate, blood pressure and heart vagal tone were not modified by capsaicin. It is concluded that a selective activation of nociceptive primary afferent fibers of the skin by capsaicin produces a central submodality-dependent facilitation of an autonomic vasoconstriction response to noxious stimulation in humans. This central facilitation can be explained by segmental excitability changes of afferent interneurons at the spinal cord level.

Adult

A selective suppression of human pain sensitivity by carbon dioxide: central mechanisms implicated.

The effect of breathing CO2 on somatic sensitivity was studied in human subjects. Healthy humans breathed room air, 100% O2, or CO2 (5% or 8% in O2). Thresholds to heat pain, mechanical pain, electrically evoked pain, and electrically evoked perception were measured using psychophysical techniques. Also, the effects on sensory and affective components of experimental ischaemic pain, alertness and on cardiovascular parameters were observed. In addition, the effect of CO2 on heat pain threshold was determined in the ischaemic limb to exclude the possibility that the threshold elevation was due to an action on primary afferent fibres. Naloxone (0.8 mg), dexamethasone (0.1 mg) or placebo (0.9% NaCl) were applied intravenously in double blind tests to reverse the threshold elevations. In an electrophysiological experiment the effect of CO2 on a spinal nociceptive flexion reflex evoked by an electric stimulus was measured. The CO2 produced a dose-dependent elevation of the heat pain threshold. Similarly, the sensory and affective components of experimental ischaemic pain were attenuated by CO2. The heat pain threshold was significantly elevated by CO2 in the ischaemic limb, also. However, there was no effect on thresholds to mechanically or electrically induced pain or perception thresholds to electrically evoked sensations. One hundred percent O, did not elevate the heat pain threshold. In double blind tests the heat pain threshold elevation was not significant when the naloxone or dexamethasone was administered. The threshold to electrically evoked spinal flexion reflex was not elevated by CO2. The CO2 at the current dose produced sedation, an increase in blood pressure but no change in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Steroid hormone receptors and flow cytometric DNA ploidy in ovarian carcinoma.

The biochemical and immunohistochemical estrogen (ER) and progesterone receptor (PR) content and flow cytometric DNA ploidy was analyzed in five semimalignant and 35 malignant epithelial ovarian tumours. By biochemical assay, 67% of the tumours were ER-positive (> or = 5 fmol/mg protein) and 56% were PR-positive (> or = 10 fmol/mg protein). The corresponding values by immunohistochemical assay (with a HSCORE of 10 as the cutoff level) were 22% and 27%, respectively. DNA histogram measured from paraffin embedded specimens were diploid in 20% (7/35) and aneuploid in 80% (28/35) of the malignant tumours. All semimalignant tumours were diploid. The mean receptor values in the diploid and aneuploid tumours did not differ significantly and receptor-positive and receptor-negative tumours were evenly distributed in all stages and grades. In contrast, flow cytometric DNA ploidy was clearly associated with tumour stage (G2 = 10.52, Df = 3, P = 0.015) and histological differentiation (G2 = 20.57, Df = 3, P = 0.0001).

Adult

The risk of endometrial cancer in diabetic and hypertensive patients: a nationwide record-linkage study in Finland.

The risk of endometrial cancer (EC) in diabetics and hypertensives was studied as part of the planning of a trial of the efficacy of screening for EC. Two nationwide registers, the Finnish Cancer Registry and the Social Insurance Institution's (SII) population register, were linked to obtain 1715 EC patients diagnosed during 1970-1974 with individually matched controls. Data on the right for state-reimbursed medication for diabetes or hypertension prior to the case's cancer diagnosis was obtained from the SII's population register and was used as indicator of the diseases in question. Diabetes was a strong and hypertension a relatively weak risk factor for EC. The relative risk for the association of EC with diabetes was 4.1 (95% confidence limits 2.7 and 6.9) and with hypertension 1.6 (95% confidence limits 1.3 and 2.1). Diabetics and hypertensives are identifiable risk groups for EC in Finland. Diabetics form a suitable target population for a trial of the efficacy of screening for EC.

Adult

Capsaicin-induced central facilitation of a nociceptive flexion reflex in humans.

The effect of selective activation of nociceptive primary afferent fibers by capsaicin on a nociceptive lower limb flexion reflex was studied in healthy human subjects. Capsaicin (1%) applied topically to the skin produced a burning spontaneous pain sensation and allodynia in the treated region and in its immediate vicinity. Capsaicin applied to the distal innervation area of the sural or saphenous nerve produced a significant decrease of the threshold for the nociceptive limb flexion reflex induced by electric stimulation of the proximal sural nerve trunk, and this threshold decrease was rapidly attenuated by a cool compress concomitantly with the attenuation of the capsaicin-induced spontaneous pain. The latency of the flexion reflex response was not changed by capsaicin. The non-nociceptive H-reflex was not modified by capsaicin. It is concluded that a selective activation of nociceptive primary afferent fibers of the skin by capsaicin produces a central facilitation of a nociceptive flexion reflex in humans. This facilitation is selective on the nociceptive reflex and depends, at least partly, on the on-going afferent barrage in C-fibers.

Administration, Topical

Mass screening for endometrial cancer directed in risk groups of patients with diabetes and patients with hypertension.

BACKGROUND: The interest in mass screening programs for the early detection of endometrial cancer (EC) has grown with the rising incidence of this disease. Preliminary programs directed at asymptomatic women with only one risk factor, i.e. age, have not been cost-effective. METHODS: In the current study, 597 asymptomatic women from 45-69 years of age with diabetes and/or hypertension were screened by Vabra (Berkeley Medevices Inc., Berkeley, CA) aspiration. RESULTS: Among the women with diabetes, 6.3% preinvasive lesions of the endometrium were found. This is significantly more than the rate among women with hypertension, which was 1.3% (P < 0.01). CONCLUSIONS: Regular mass screening programs for the early detection of EC should be directed at asymptomatic diabetic women 45 years of age or older. This study does not indicate that similar screenings would be effective for women with hypertension.

Aged

Chemosensitizing effect of an antiestrogen, toremifene, on ovarian cancer.

The chemosensitizing effect of an antiestrogen, toremifene, was studied on 2 human ovarian cancer cell lines in vitro and on 3 fresh surgical ovarian tumor explants with the aid of the subrenal capsule assay (SRCA). Also, 11 patients with secondarily drug resistant, recurrent gynecologic cancer (8 ovarian and 3 uterine cancers) were treated with 240 mg toremifene daily for 1 week before each course of cytostatics. Toremifene potentiated the effect of doxorubicin on both cell lines. This was also the case on 1 cell line that was not completely resistant to doxorubicin. The SRCA showed a clear potentiating effect of toremifene only on the tumor overtly resistant to the combination of cisplatin, doxorubicin, and cyclophosphamide. Of the 11 patients treated with toremifene and cytostatics, the response of 8 patients was evaluable: 3 had partial response, 3 no change, and 2 progressive disease. Toremifene seems to have a chemopotentiating effect on gynecologic drug-resistant tumors.

Aged

Increased sexual behavior in male Macaca arctoides monkeys produced by atipamezole, a selective alpha 2-adrenoceptor antagonist.

The effect of a highly selective and potent alpha 2-adrenoceptor antagonist, atipamezole, on sexual behavior was studied in three stumptail macaques (Macaca arctoides). Following IM administration of atipamezole or saline control, the behavior of the male monkey with a female monkey was observed for 30 min. Atipamezole dose dependently (0.01-0.15 or 0.30 mg/kg) produced a significant increase in the number of ejaculations in all three monkeys, including an old one with decreased sexual activity in control conditions. Both ejaculations obtained by copulation and masturbation were increased. It is concluded that atipamezole is effective in increasing sexual behavior in male stumptail monkeys.

Adrenergic alpha-Antagonists