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In search for a potent dilatator or deactivator of constriction of cerebrovascular smooth muscle, the effects of a specific antagonist of the calcium influx necessary for the excitation-contraction coupling process was studied on isolated human pial arteries. The arteries were constricted by addition of noradrenaline, 5-hydroxytryptamine, human plasma or blood. All these agents induced a strong contraction which could effectively be reduced by addition of the Ca++-antagonist, nifedipine, to the organ bath. It is suggested that calcium antagonists might be of value in the treatment of cerebrovascular spasm following a subarachnoid hemorrhage.

Sixty-eight patients with giant cell arteritis (GCA) are described. In 42, histological evidence of arteritis was recorded at biopsy of a temporal artery. Twenty-six patients were included according to clinical criteria. In 20 patients the onset of illness was associated with an infection. The first symptom was: in 30 patients, muscle pains; in 14, fever; in 11, headache with temporal localization, and in 13 patients, tiredness and anorexia. In all, 50 patients had muscular symptoms and 30 had symptoms of localized temporal arteritis. In 5 patients neither muscular symptoms nor localized arteritis were found. A high erythrocyte sedimentation rate was seen in all cases and elevated platelet count was found in 24 patients. Abnormal liver function was a common finding, whereas impaired renal function was not observed. In 8 cases reversible eye symptoms were noted and reduced hearing capacity was demonstrated in 5 patients.

The natriuretic/diuretic effect of felodipine was investigated in 2 studies. The first was performed as an open study using intravenous and oral felodipine in healthy male subjects. The second was a double-blind study where a high and a low dose of oral felodipine were given to hypertensive patients on long term treatment with beta-blockers; the different doses of felodipine were chosen to decrease and to have no effect on the blood pressure, respectively. In both studies an oral placebo solution was used as a reference. Felodipine caused a significant increase in natriuresis. Compared with placebo and corrected for total 24-hour excretion, the sodium output during the first 4 hours after drug administration was increased by 219 +/- 53% (mean +/- SEM) after intravenous administration in healthy subjects (p less than 0.01) and by 80 +/- 43% in the first 3 hours after the high dose in hypertensive patients (p less than 0.05). For the same period, the urine excretion was increased by 114 +/- 38% (p less than 0.05) in the healthy subjects and by 36 +/- 22% in the hypertensive patients (not significant). However, the 24-hour excretion of urine, Na+ and K+ was not significantly changed from placebo. A significantly lower blood pressure was recorded after the higher dose (0.10 mg/kg) when given to hypertensive patients, but no such effect was seen after the lower dose (0.01 mg/kg) or in healthy subjects. The changes in diastolic blood pressure seem to be negatively correlated with the diuretic but not with the natriuretic effect.

Hand tremor, heart rate, and electrolyte, plasma (pl) insulin, blood (bl) glucose, and pl terbutaline levels were measured in 11 healthy men during infusion and oral administration of terbutaline. Infusion of terbutaline (250 micrograms) was followed by increases in pl insulin concentration and bl glucose and by a decrease in pl K. Similar metabolic changes were seen on day 1 of oral terbutaline (5 mg x 3). Heart rate was moderately increased by terbutaline over the entire period (13 days) or oral dosing. Hand tremor always increased after terbutaline, but to a lesser degree on days 4 and 13 than after the first oral dose. On day 13 there was a very small increase in pl insulin and no reduction in pl K; bl glucose increased slightly from an elevated basal level. Pl terbutaline was of similar maximum concentrations on days 1 and 13, indicating that the tolerance was mediated through reduced response of the effector organs.

The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen and haptoglobin were followed weekly during the initial phase of corticosteroid treatment in 18 patients with 19 episodes of giant cell arteritis (GCA). Fibrinogen and CRP decreased most rapidly, with normal values in 67% of the patients after two weeks of treatment. After two weeks 56% of the patients had normal ESR values and 76% after five weeks. Haptoglobin normalised most slowly, no patient having a normal value after one week, 29% after two weeks and 75% after six weeks. For routine clinical use, we found the ESR alone sufficient for monitoring the initial steroid treatment.

Intraocular pressures and optic disc hemorrhages were studied in all cases of manifest glaucoma detected in a defined population over a decade. High intraocular pressure was found to be an unreliable sign at the detection of a glaucomatous visual field defect and an unusual finding 5-10 years before. The prevalence of optic disc hemorrhages at the detection of a glaucomatous visual field defect was 33%. All but 9 of 44 persons with manifest glaucoma were found to have had at least one optic disc hemorrhage at one time or another.

The fractional release of [3H]noradrenaline was measured in rings from the rat trachea. Transmitter release was induced either by isotonic KCl (124 mM) or by 2.5 mM Ca added to a Ca-free depolarizing solution. Felodipine, a Ca antagonist (10(-4)M), had no effect on the basal release of [3H]NA whereas it reduced the overflow of transmitter caused by KCl or Ca. Diethyl-stilboestrol (25 microM), which also inhibits Ca influx in smooth muscle, had a stronger inhibitory effect than felodipine on [3H]NA release induced by high K and addition of Ca. Basal efflux of [3H]NA was increased by diethyl-stilboestrol. This increase also occurred in the absence of extracellular Ca.

During a period of three years in Göteborg, Sweden, 126 cases of giant cell arteritis (GCA) were diagnosed. Histologic evidence of arteritis was found on temporal artery biopsy in 74 (59%). The total annual incidence of GCA was calculated to be 9.3 per 100,000 inhabitants. In the age group over 50, incidence was 28.6 per 100,000. For histologically proven GCA, the incidence was 5.5 per 100,000 of the total population. The corresponding figure in the age group over 50 was 16.8 per 100,000. Twenty-six patients (21%) had a clinical presentation of temporal arteritis, and 23 (18%) had a combined picture of temporal arteritis and polymyalgia rheumatica (PMR). Sixty-seven (53%) had the PMR syndrome without any temporal symptoms, and 10 patients (8%) had a "silent" presentation with only general symptoms. The PMR syndrome was more common among women with GCA (79%) than among men (56%). The group of patients without muscular symptoms contained an equal number of men and women. Eye complications were seen in 15 patients (12%). In 6, the ocular symptoms were transient, while 9 suffered from permanent loss of vision. In 3 of these patients, temporal artery biopsy revealed no evidence of arteritis, and 5 had no clinical signs of localized temporal arteritis.

A simple method to estimate the mean fitness of human translocation carriers is described. The method is based on information about the inheritance pattern of the translocations. This kind of data can be obtained from the surveys of the chromosome constitutions of new-born babies. The following fitness estimates are obtained: D/D translocation carriers, 0-94; D/G translocation carriers, 0-83; and reciprocal translocation carriers, 0-67. The estimates are rather uncertain due to the scarcity of information, but they are consistent with the expected results. More accurate estimates will be obtained in the future when more data on translocation carriers are available and the cytological classification of the different translocations becomes more exact.

The levels of IgG, total complement, and complement factors C3 and C4 were elevated in serum from patients with giant-cell arteritis as compared to a control group of patients in the same range of age. No increase of the IgM concentration was found. The concentration of IgA was higher in men with giant-cell arteritis as compared to men in a control group. This increase of IgA was not seen in women. There were no statistically significant differences in any of the studied variables between those with a histologically verified arteritis on temporal biopsy specimens and those without.

The neuropeptide substance P (SP), which is released from sensory C-fibres after stimulation by chemical irritants. accelerates mucociliary activity in rabbit maxillary sinus in vivo. In order to investigate the mechanism behind this finding, we recorded ciliary beat frequency (CBF) in vitro from various respiratory explants by a photoelectric technique. It was noticed that ciliated cells from the maxillary sinus displayed a higher beating frequency than cells from the trachea and the bronchus, in that order. SP 10(-10)-10(-4) M did not influence the CBF in explants from rabbit maxillary sinus, rabbit trachea and main bronchi, guinea-pig trachea and human adenoids. Neurokinin A (NKA) 10(-6)-10(-5) M, which is also thought to be released from sensory C-fibres, did not influence the CBF in guinea-pig trachea. Neither did the C-fibre stimulant capsaicin 10(-8)-10(-4) M increase CBF in explants from human adenoids. The present findings indicate that the mucociliary effect of SP in vivo is not mediated by an effect on the cilia themselves.

The uterotonic effects of arginine8-vasopressin (AVP) have been studied on uterine strips from non-pregnant women. Concentration-dependent contractions could be recorded over a 10 min period in the presence of AVP (5.5.10(-10)-3.10(-7) M); the most reproducible recordings were obtained with tissue from the inner part of the myometrium. Analogues of AVP and oxytocin (OT), modified at positions 1 (2-hydroxy-3-mercaptopropionic acid, deamino-3-mercaptopropionic acid), 2 (Phe), 4 (Arg, Val), 7 (Sar) or 8 (Orn) were synthesized and tested for uterotonic activity on human and rat uterine strips, and for vasopressor and antidiuretic activity in the rat in vivo. There was a positive correlation between the activity of these analogues on non-pregnant human myometrial tissue with that in the rat vasopressor assay (r = 0.86, P less than 0.01) but none with their activity in the antidiuretic assay. For example, [Mpa1,D-Arg8]vasopressin had more than twice the antidiuretic activity of AVP but less than 0.2% of its pressor or human uterotonic potency (Mpa = 3-mercaptopropionic acid). Correspondingly, the specific pressor analogue [Hmp1,Phe2,Orn8]OT was as potent as AVP on the human uterus, but had less than 3% of its antidiuretic activity (Hmp = 2-hydroxy-3-mercaptopropionic acid). There was no correlation between the uterotonic activities of AVP or its analogues when non-pregnant human and rat tissues were compared, indicating that rat uterine tissue is a poor guide when testing analogues intended for clinical use in non-pregnant women.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulating immune complexes were found in 2 of 15 patients with giant cell arteritis (GCA) by using a solid phase Clq enzyme linked immunoabsorbent assay (ELISA). The prevalence in controls was 5%. Rheumatoid factor could be demonstrated in 2 out of 27 patients and in 11% of the controls by using a similar ELISA technique. The prevalence of T cells in blood was similar in 25 patients with GCA and in controls. The blood lymphocyte blastogenic response to the mitogens, phytohaemagglutinin, concanavalin-A, and pokeweed mitogen did not differ in 25 untreated patients compared with controls. Stimulation of lymphocytes by arterial homogenates was tested in 8 patients. In no case could a significant simulation by obtained. We conclude that immune complexes and rheumatoid factors are present in the same low frequency in GCA patients as in the normal population, and that the studied parameters of cellular immunity appear to be normal.

Profiles of plasma GH, plasma somatomedin-C and serum PRL concentrations as well as serum GH response to iv TRH were determined in 11 patients with acromegaly before and 10 days after surgery. Blood for profile determinations was drawn from a peripheral vein with a continuous withdrawal pump changing the recipient tube at 30-min intervals. Before surgery all patients had high plasma GH concentrations with irregular peaks and somatomedin-C concentrations were elevated. The response to TRH was abnormal in 8 patients. Three patients had slightly elevated PRL concentrations and one had high PRL concentration (6900 mU/l). Ten days after surgery GH concentrations were still high in 2 patients (greater than 5 mU/l), as were somatomedin-C concentrations (3.2 and 2.4 U/l, respectively). In 3 patients basal GH concentrations were less than 5 mU/l and somatomedin-C concentrations were normal, but there were no major peaks in plasma GH concentrations. In 2 patients major peaks in GH concentrations appeared after surgery, but basal GH concentrations were 1.9 and 0.95 mU/l, respectively. One patient with hyperprolactinemia still had slightly elevated PRL concentration (486 mU/l), but the response to TRH was normalized. Finally, in 4 patients, mean GH concentrations were markedly reduced, somatomedin-C concentrations normalized and apparently normal plasma GH profiles appeared with low or undetectable basal levels separating major peaks. The results indicate that in some patients with acromegaly apparently normal GH secretion can be demonstrated 10 days postoperatively. Characterization of circadian GH rhythms during the early postoperative stage may contribute to the evaluation of the effect of surgery.

Giant cell arteritis (GCA) is a vascular inflammatory disease characterized by accumulations of T lymphocytes and macrophages in the arterial wall. In order to characterize the immune response in GCA, we have analysed temporal artery biopsies using a double-staining immunofluorescence method and studied T lymphocytes in peripheral blood with a fluorescence-activated cell sorter (FACS). HLA-DR was expressed on 28% (range 16-42%) of all T lymphocytes in the wall of the inflamed temporal artery, but only on average on 6% of peripheral blood T lymphocytes, indicating a high degree of local T cell activation in the inflammatory lesion. The proportions of T lymphocytes, T helper/inducer and T suppressor/cytotoxic cells in the blood of GCA patients before treatment with prednisolone did not deviate from those in normal individuals, but there was a minor increase in T helper cells after initiation of steroid therapy. The number of T helper cells expressing HLA-DR antigen and IL-2 receptor was not altered after 6-10 days of treatment with prednisolone. We found no evidence of HLA-DR expression by arterial smooth muscle cells in the GCA lesions, suggesting that these cells do not serve as antigen-presenting cells in GCA.

Sixty-two moderately depressed elderly in- and out-patients were administered 80 mg ACTH 4-9 analogue (Org 2766) or placebo daily for 4 weeks in a double-blind interindividual comparison. Patients were rated on days 0, 15 and 29 with the Hamilton Psychiatric Depression Rating Scale (HPDRS), The Hamilton Anxiety Scale (HAS) and the Sandoz Clinical Assessment Geriatric Scale (SCAG). After 4 weeks 23 patients crossed over to the opposite treatment for a further 2 weeks. A statistically significant reduction in the severity of depression and anxiety was found in both treatment groups. No statistically significant differences were found between the treatment groups, when comparing scores for each item and total scores of HPDRS, HAS and SCAG on day 0, 15 or 29. Nor were there any statistically significant differences after the cross-over. Somatic examination and laboratory screenings before and at the end of the study did not reveal any pathological changes. No side effects were recorded.

Elderly ophthalmic out-patients that had visited an eye-clinic were searched in a population register 7 years later. Observed numbers of survivors were compared with those expected according to appropriate life tables. Most observed numbers of survivors came close to the expected ones. Patients, aged more than 80 years when visiting the eye-clinic, had, however, a consistently increased survival rate. Glaucoma patients, less than 80 years old, had a slightly (not significantly) lower survival rate than expected.

The mechanical responses to potassium of the rabbit and rat uterus were different. The force of a potassium-induced contracture showed a rapid decline in the rabbit uterus, whereas it was fully maintained for a long period in the rat uterus. The increase in 45Ca influx following exposure to high KCl was substantial and similar (0.3 mmol kg-1) in both rat and rabbit uterus. Calcium uptake in post nuclear supernatant (PNS) from the rat myometrium was significantly lower than that from the rabbit myometrium in both the rate and capacity of uptake. This uptake was reduced to about 10% in the presence of sodium azide in PNS from both rat and rabbit myometria. Both the rate and capacity of calcium uptake by mitochondria isolated from PNS of rat myometrium were considerably lower than that by rabbit myometrial mitochondria. Microsomes isolated from rat and rabbit PNS had very low capacity for calcium uptake compared with mitochondria. No difference was found in the rate or the capacity of uptake between the rat and the rabbit myometrial microsomes. The data support the argument for a role of mitochondria in myometrial relaxation and further provide evidence for a considerable species difference in calcium uptake by myometrial mitochondria.

Ninety patients with giant cell arteritis (GCA) were followed for 9-16 years after diagnosis. Corticosteroids were given to all but one patient. Forty-two patients died during the observation period (27 women and 15 men). The survival was compared with that in the general population and found not to be reduced among the GCA patients. In fact, we found a lower mortality than expected after five years from diagnosis (p less than 0.05). We did not see any increase in deaths due to vascular or malignant diseases in our patients.