Subcutaneous blood flow in psoriasis.

The simultaneously recorded disappearance rates of 133Xe from subcutaneous adipose tissue in the crus were studied in 10 patients with psoriasis vulgaris using atraumatic labeling of the tissue in lesional skin (LS) areas and symmetrical, nonlesional skin (NLS) areas. Control experiments were performed bilaterally in 10 younger, healthy subjects. The subcutaneous washout rate constant was significantly higher in LS, 0.79 +/- 0.05 min-1 X 10(2) compared to the washout rate constant of NLS, 0.56 +/- 0.07 min-1. 10(2) (p less than 0.05), or the washout rate constant in the normal subjects, 0.46 +/- 0.17 min-1 X 10(2) (p less than 0.01). The mean washout rate constant in NLS was 25% higher than the mean washout rate constant in the normal subjects. The difference was, however, not statistically significant. Differences in the washout rate constants might be due to abnormal subcutaneous tissue-to-blood partition (lambda) in the LS--and therefore not reflecting the real differences in the subcutaneous blood flow (SBF). The lambda for 133Xe was therefore measured--using a double isotope washout method (133Xe and [131I]antipyrine)--in symmetrical sites of the lateral crus in LS and NLS of 10 patients with psoriasis vulgaris and in 10 legs of normal subjects. In LS the lambda was 4.52 +/- 1.67 ml/g, which was not statistically different from that of NLS, 5.25 +/- 2.19 ml/g (p less than 0.05), nor from that of normal subcutaneous tissue, 4.98 +/- 1.04 ml/g (p less than 0.05). Calculations of the SBF using the obtained lambda values gave a significantly higher SBF in LS, 3.57 +/- 0.23 ml/100 g/min, compared to SBF in the NLS, 2.94 +/- 0.37 ml/100 g/min (p less than 0.05). There was no statistically significant difference between SBF in NLS and SBF in the normal subjects. The increased SBF in LS of psoriatics might be a secondary phenomenon to an increased heat loss in the lesional skin.

Regulation of local subcutaneous blood flow in patients with psoriasis and effects of antipsoriatic treatment on subcutaneous blood flow.

Local regulation of the doubled subcutaneous blood flow (SBF) rates in psoriatic lesional skin was studied in 8 patients using a traumatic epicutaneous 133Xe labeling washout technique. Venous stasis of 40 mm Hg induced a significant reduction in the SBF (-34%, p less than 0.01), i.e., a normal vasoconstrictor response. Limb elevation of 40 cm above heart level induced no statistical changes in the SBF (p = 0.50), i.e., a normal local autoregulation response. This indicates normal, local regulation mechanisms of SBF in psoriasis. In another 8 patients, the effect on SBF of a 4-week antipsoriatic treatment with tar was studied in lesional and symmetrically nonlesional skin areas. One patient was clear of psoriasis on day 22, and was followed only to that time. The mean pretreatment SBF in lesional skin areas was 3.87 +/- SD 0.78 ml X (100 g X min)-1, which was not statistically different from measurements on days 3, 7, 14, and 21 after treatment had started. Between day 21 and day 28, the SBF decreased significantly to 3.38 +/- SD 0.78 ml X (100 g X min)-1, p less than 0.05. The difference between the pretreatment SBF and SBF at the end of treatment was statistically significant, p less than 0.05. The changes in SBF in symmetrically nonlesional skin areas were statistically nonsignificant during the period of treatment. Pretreatment SBF was 2.60 +/- SD 1.08 (N = 8), and on day 28 was 1.91 +/- SD 0.74 ml X (100 g X min)-1 (N = 7). However, the tendency of a decreasing SBF at the end of treatment was a clear trend, since SBF in 6 of 7 patients decreased during the third week and in the patient who was discharged on day 22, a decrease in the SBF was observed on days 14 and 21. The week-to-week changes in the SBF of lesional and nonlesional skin sites were parallel, r = 0.93, p less than 0.02. The decrease in SBF in psoriatics during successful antipsoriatic treatment might be a secondary thermoregulatory phenomenon due to a decreasing cutaneous blood flow.

Local regulation of cutaneous blood flow in psoriasis.

Local regulation of cutaneous blood flow (CBF), i.e., the venoarteriolar reflex mechanism and the autoregulation response, was studied in 27 patients with psoriasis using atraumatic epicutaneous 133Xe-labeling tracer washout technique. Venous stasis of 40 mm Hg induced a significant reduction in CBF--as in normal subjects (i.e., a vasoconstrictor response)-in both involved psoriatic skin (0.47 +/- SEM 0.04, p less than 0.0001) and uninvolved psoriatic skin (0.38 +/- SEM 0.03, p less than 0.0001). The vasoconstrictor response to neural blockade with lidocaine was investigated in two control experiments in psoriatic skin. It was found to be normal: neural blockade with lidocaine 2 cm outside the measured field did not affect the vasoconstrictor response, whereas local infiltration with lidocaine did block the vasoconstrictor reflex. Limb elevation of 40 cm above heart level induced a 2-fold significant increase in the CBF of involved psoriatic skin in 10 patients. This response is a paradoxical deviation from normal local autoregulation of the CBF (p less than 0.002). Limb elevation had no significant influence on CBF of uninvolved psoriatic skin, indicating a normal autoregulation of the CBF. The paradoxical increase in CBF during limb elevation in involved psoriatic skin was not influenced by local neural blockade with lidocaine, or by local neural and vascular, smooth muscle blockade obtained by injection of lidocaine and papaverine. The results indicate that the reason for this paradoxical phenomenon might be due to the special morphology of the capillaries of involved psoriatic skin.

Cutaneous blood flow during white dermographism in patients with atopic dermatitis.

Cutaneous blood flow was determined before and immediately after rubbing the skin of 7 patients with atopic dermatitis and 6 normal subjects, using the local atraumatic 133Xe-method. In the atopic patients the rubbing of eczematous skin produced white dermographism and simultaneously the cutaneous blood flow decreased in all the patients from 15.2 +/- SEM 1.7 ml/100 g . min before the rubbing to 6.2 +/- SEM 1.6 ml/100 g . min during white dermographism (p less than 0.002). In all the normal subjects the rubbing stimulus was followed by an increase in blood flow from 5.2 +/- SEM 0.6 to 24.4 +/- SEM 3.1 ml/100 g . min (p less than 0.001), although red dermographism was not seen in all. It is concluded that the most reasonable explanation for the pallor during white dermographism is the reduced cutaneous blood flow.

Local variation in cutaneous and subcutaneous blood flow measured by CdTe(C1) minidetectors in normal and psoriatic skin.

The accuracy of the 133Xe washout method and the validity of newly developed cadmium telluride CdTe(Cl) minisemiconductor detectors were estimated by performing comparative, simultaneous measurements of both cutaneous (CBF) and subcutaneous (SBF) blood flow using 2 conventional scintillation sodium iodide NaI(Tl) and CdTe(Cl) detectors over the same radioactive depot in each of 10 individuals. The accuracy of the 133Xe washout method was found to be 13-15% (C.V.) for the CBF measurements and 9-12% (C.V.) for the SBF measurements. The CdTe(Cl) detectors, which have a weight of 20 g and were attached directly over the radioactive depot, may replace stationary NaI(Tl) detectors placed 20 cm from the depot for measurements of both CBF and SBF. Two CdTe(Cl) detectors were used for estimations of the local variation in CBF and SBF within a distance of 5 cm in normal skin of 10 individuals. The C.V. was 7% for the CBF measurements and 18% for the SBF measurements. Measurements of CBF and SBF were performed in 6 psoriatic patients who, after about 1 week of antipsoriatic treatment with beech tar, developed typical Woronoff rings. The local CBF differed significantly from the center of psoriatic plaques to the margin, in the Woronoff ring, and in nonlesional skin. In contrast, SBF was remarkably equal within the plaque and in the Woronoff ring. The color of the Woronoff ring cannot be ascribed to a local cutaneous vasoconstriction. Cutaneous blood flow in chronic stable, lesional psoriatic skin was significantly lower than previously published values for active lesional psoriatic skin, but significantly higher than CBF in normal individuals. Measurements of CBF in tetrahydrofurfuryl nicotinic acid (Trafuril)-treated skin showed higher values than measurements of CBF in the postischemic hyperemia period both in normal and in lesional psoriatic skin. Trafuril induced a significant increase of CBF in both lesional and nonlesional skin. The high CBF rates in lesional psoriatic skin are not due to a maximally, passively dilated vascular bed.

Cutaneous and subcutaneous blood flow in non-lesional skin of patients with minimal psoriatic skin manifestations.

Cutaneous and subcutaneous blood flow (CBF, SBF) were studied in non-lesional psoriatic skin (NLS) of 10 patients with only minimal psoriatic skin manifestations, using the local 133Xe washout method. Measurements of the CBF and SBF in the NLS of the patients and 10 normal individuals yielded no statistically significant differences. The results of the present study indicate that the activity of psoriasis can be monitored by the CBF measurements in the NLS, since previously published values for CBF of NLS have shown increasing values with increasing psoriatic activity. The significance of these findings may be more evidence of humoral factors playing a role in the pathogenesis of the disease. The tissue-to-blood partition coefficient for 133Xe was calculated on the basis of biochemical estimations of the relative content of lipids, proteins, and water in skin biopsies from non-lesional skin sites of 8 psoriatic patients. The relative content of lipids, proteins, and water was normal. Thus, the normal 133Xe partition coefficient of 0.7 ml/g should be used for measurements of the CBF in NLS.

The effects of antipsoriatic treatment on cutaneous blood flow in psoriasis measured by 133Xe washout method and laser Doppler velocimetry.

In 8 patients with psoriasis vulgaris, the cutaneous blood flow (CBF) was measured simultaneously in both involved and uninvolved psoriatic skin before (i.e., on the first day of hospitalization) and on the 3rd, 7th, 14th, and 28th days of treatment with tar. The 133Xe washout method was used after epicutaneous labeling and compared to the laser Doppler velocimetry (LDV) technique. Control experiments were performed in 10 normal individuals. Before treatment the mean CBF in involved psoriatic skin was 62.6 +/- 18.7 SD ml X (100 g X min)-1, which is significantly higher than CBF of uninvolved skin in psoriatic patients, 9.5 +/- 4.0 SD ml X (100 g X min)-1, (p less than 0.01) and is 13.6 times higher than CBF in the normal individuals (p less than 0.01). Fifty hours following onset of treatment (i.e., after only 2 applications of tar), mean CBF of the involved psoriatic skin had decreased significantly to 35.0 +/- 13.9 SD ml X (100 g X min)-1, (p less than 0.01), which was not statistically different from the CBF on the 7th day. During the following weeks, the CBF in involved psoriatic skin decreased at a more moderate rate than that observed during the first week and was 15.0 +/- 6.1 SD ml X (100 g X min)-1 on the 28th day. This value is not significantly different from the CBF of uninvolved skin in these patients. At the end of treatment, the CBF of the uninvolved skin had decreased significantly (p less than 0.05) in all the patients to values similar to those observed in the skin of normal individuals. A parallel decline was observed in a clinical psoriatic score index; however, it is not known whether the observed decrease in CBF was preceded or succeeded by the clinical improvement. A comparison of the 133Xe measurements and LDV measurements in the normal individuals by linear regression analysis yielded a correlation coefficient of -0.24 (N = 20, p greater than 0.05). In the skin of psoriatic patients the correlation coefficient was 0.01, (N = 47, p greater than 0.05) for unaffected skin, and 0.61 (N = 47, p less than 0.001) in the involved psoriatic skin sites. The LDV measurements did not reflect changes in the uninvolved skin in psoriatic patients during treatment and resulted in a remarkably high C.V. in the bilateral measurements of skin in normal individuals (43.8%) compared to the C.V. of 133Xe flow measurements (14.8%). It is concluded that while the LDV method gives a rough estimate of blood flow in cutaneous tissue with a high capillary perfusion rate, inaccurate measurements are made in skin areas with normal to twice the normal CBF range.

Cutaneous blood flow in psoriasis.

The disappearance rate of 133Xe was studied in 20 patients with psoriasis vulgaris, using an epicutaneous labeling technique in involved skin lesions or normal-appearing skin of the proximal extensor site of the forearm. Control experiments were performed in 10 normal subjects. Calculations of the cutaneous blood flow (CBF) in psoriatic skin lesions were performed using a tissue-to-blood partition coefficient for 133Xe, lambda c,pso, of 1.2 ml/100 g/min. lambda c,pso was estimated after the relative content of water, lipids, and proteins had been analyzed in psoriatic skin biopsies of 6 patients with untreated psoriasis. The mean relative content of water was markedly reduced to 23.5 +/- 1.5% (SEM), and lipids and proteins were markedly increased to 2.5 +/- 0.7% and 74.0 +/- 2.2, respectively, compared to previously published data for normal skin (water 72.5%, lipids 1%, proteins 26.5%). Mean CBF in untreated psoriatic skin was 63.5 +/- 9.0 ml/100 g/min. This was significantly higher than the mean CBF in 10 normal subjects, 6.3 +/- 0.5 ml/100 g/min (p much less than 0.0001). Mean CBF in normal-appearing skin in patients with psoriasis was 11.0 +/- 1.3 ml/100 g/min. This was significantly higher than CBF in normal subjects (p less than 0.0002).

Subcutaneous blood flow in early male pattern baldness.

The subcutaneous blood flow (SBF) was measured by the 133Xe washout method in the scalp of 14 patients with early male pattern baldness. Control experiments were performed in 14 normal haired men matched for age. The SBF in the scalp of the normal individuals was about 10 times higher than previously reported SBF values in other anatomical regions. In patients with early male pattern baldness, SBF was 2.6 times lower than the values found in the normal individuals (13.7 +/- 9.6 vs 35.7 +/- 10.5 ml/100 g/min-1). This difference was statistically significant (p much less than 0.001). A reduced nutritive blood flow to the hair follicles might be a significant event in the pathogenesis of early male pattern baldness.

The carcinogenic effect of UVA irradiation.

The carcinogenic effect of UVA radiation (from Philips black light tubes filtered through a 2 mm-thick glass plate to eliminate the radiation below 320 nm) was studied in 7 groups of 25 lightly pigmented hairless mice. Irradiation with a moderate daily dose of combined UVB and UVA for 3 months induced a tumor incidence of 0.22 after 58 weeks. When the combined UVB and UVA irradiation was followed by filtered UVA for 2, 4, or 6 months, the tumor incidence was marginally significantly increased to 0.42, 0.48, and 0.50 (p less than 0.05), respectively. However, irradiation with the moderate dose of combined UVB and UVA induced a slight but not significantly lower tumor incidence as compared to UVB alone (0.22 vs 0.30, p greater than 0.1). UVA alone induced no tumors. It thus appears that in hairless mice initially exposed to a combination of UVB and UVA, subsequent continued irradiation with UVA increases tumor incidence. While only marginally statistically significant, tumor incidence in these animals seems to increase with duration and hence total UVA exposure. Furthermore, it is suggested that the photoaugmentative carcinogenic effect of UVA irradiation from unfiltered UVA bulbs can be reduced by attenuating the shorter wavelengths of the radiation.

Tolerance of the liver to the effects of Yttrium-90 radiation.

There are no reliable data documenting the tolerance of the human liver to ionizing radiation from a continuous Yttrium-90 source. As Yttrium-90 incorporated into microspheres is being used to treat patients with liver cancer, it is imperative that the tolerance of the human liver to this form of radiation damage be determined. Four patients with metastatic liver cancer were treated with Yttrium-90 to deliver radiation doses above that considered tolerable when given by conventional external sources. Patients were monitored with serial estimations of liver function tests and between 7 and 9 months after treatment liver biopsies were performed. Histological examination of the liver biopsies confirmed only minimal changes in the normal liver parenchyma. These data indicate that the human liver may tolerate relatively large radiation doses when delivered by Yttrium-90 microspheres embedded in the liver parenchyma as a number of discrete point sources.

Dose distribution following selective internal radiation therapy.

Selective Internal Radiation Therapy is the intrahepatic arterial injection of microspheres labelled with 90Y. The microspheres lodge in the precapillary circulation of tumor resulting in internal radiation therapy. The activity of the 90Y injected is managed by successive administrations of labelled microspheres and after each injection probing the liver with a calibrated beta probe to assess the dose to the superficial layers of normal tissue. Predicted doses of 75 Gy have been delivered without subsequent evidence of radiation damage to normal cells. This contrasts with the complications resulting from doses in excess of 30 Gy delivered from external beam radiotherapy. Detailed analysis of microsphere distribution in a cubic centimeter of normal liver and the calculation of dose to a 3-dimensional fine grid has shown that the radiation distribution created by the finite size and distribution of the microspheres results in an highly heterogeneous dose pattern. It has been shown that a third of normal liver will receive less than 33.7% of the dose predicted by assuming an homogeneous distribution of 90Y.

Dominant distal arthrogryposis in a Maori family with marked variability of expression.

The index case was a Maori bushman who presented with severe congenital spinal stenosis and manifestations of distal arthrogryposis. His offspring and 8 of his 9 sibs and most of their offspring were interviewed and examined. Of those examined 7 individuals with definite and 2 with probable distal arthrogryposis were identified in 4 of the families. A tenth relative with distal arthrogryposis and contractural arachnodactyly had died. There was marked variability in the severity and nature of manifestations with 2 having severe hand and foot involvement in addition to craniofacial changes compatible with a diagnosis of Freeman-Sheldon syndrome. Other apparently unrelated hereditary disorders in the family included ectrodactyly, biliary atresia, and Brachmann-de Lange syndrome. This is the first report of arthrogryposis in a Maori family.

Patch test responses evaluated by cutaneous blood flow measurements.

We measured the cutaneous blood flow in positive standard patch test reactions by use of the laser-Doppler technique. The results were compared with conventional visual readings to develop a quantitative method. Compared with the basal blood flow in negative or nontested sites, the blood flow was significantly increased about fivefold in the doubtful reactions (?+), and about tenfold in both weak (1+) and strong (2+) positive reactions. The blood flows in the 1+ and 2+ reactions did not differ significantly from each other. No 3+ positive reactions were measured. We conclude that this method might be used to separate negative, doubtful, and positive reactions, whereas weak and strong positive reactions have to be differentiated by other means.

Carcinogenic effect of sequential artificial sunlight and UV-A irradiation in hairless mice. Consequences for solarium 'therapy'.

The carcinogenic effect of artificial UV sunlight followed by UV-A irradiation in human solaria doses has been studied with the use of the hairless mouse as an animal model. Artificial sunlight exposure alone induced only a moderate skin tumor incidence (animals with at least one tumor) of 0.15 after one year, and UV-A irradiation alone induced no tumor formation. However, the combination of artificial sunlight exposure and subsequent UV-A irradiation significantly increased the tumor incidence to 0.72. We conclude that, in humans, tanning with UV-A for cosmetic purposes may not be an innocuous procedure.

Pulmonary hypertension in systemic lupus erythematosus: a report of four cases.

Overt pulmonary hypertension in systemic lupus erythematosus (SLE) is rarely reported. We have documented 4 such patients, all of whom had severe extrapulmonary manifestations of the disease and also Raynaud's phenomenon. The relationship between Raynaud's phenomenon and pulmonary hypertension in SLE is borne out by a review of the literature. A common vasospastic aetiology is suggested.

Articular mobility in ballet dancers. A follow-up study after four years.

A follow-up study of ballet dancers was conducted to determine the influence of 4 years additional training on articular mobility using Beighton's method. The score increased in 25 (45.5%) of the 55 dancers reexamined. Acquired forward flexion accounted for this increase in 21 (84%) of the 25 dancers. These 21 dancers had had significantly less training than had the 30 dancers who could forward flex when examined initially (P less than 0.0001), showing that forward flexion is acquired through training. There were significantly more hypermobile individuals among dancers who had continued dancing than among those who had stopped (P less than 0.03). However, only 2 (16.7%) of 12 dancers who had progressed in their careers were hypermobile. We conclude that 1) most ballet dancers are able to forward flex, 2) forward flexion is usually acquired and develops after 4 or more years of training, 3) the mobility score may assist in predicting who will continue dancing, but that 4) there is no association between hypermobility and dancing excellence.

Prospective 153Sm-EDTMP therapy dosimetry by whole-body scintigraphy.

Samarium-153 ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP) effectively palliates painful bony metastases, but the standard recommended administered activity of 38 MBq.kg-1 may lead to significant myelotoxicity. Prospective individual dosimetry by urine collection and counting allow the bone marrow radiation dose to be limited to 2 Gy. Our novel whole-body scintigraphic method for prospective dosimetry was compared with the 5 h urine collection technique in 10 patients with bone metastases. Anterior and posterior whole-body images were obtained using identical acquisition parameters 10 min and 5 h after the intravenous injection of 740 MBq 153Sm-EDTMP. Total counts in each imaging study were corrected for background activity and time of injection and the bone activity at 5 h was determined. Bone activity was also calculated from a complete urine collection over 5 h, and these two values were compared. MIRD formulae were applied to calculate the radiation absorbed dose to the bone marrow from the injected activity. The total activity delivering a dose of 2 Gy to the bone marrow was then determined and constituted the amount given for therapy. Values for bone activity determined by imaging and by urine counting were concordant in all patients (correlation coefficient = 0.98). The total administered activity of 153Sm-EDTMP predicted on a 2 Gy bone marrow dose varied between 35 and 63% of the standard recommended regimen of 37 MBq.kg-1 and pain relief was experienced by eight of the ten patients. Administration of 153Sm-EDTMP according to the supplier's recommendations would have delivered bone marrow doses of 3.27-5.90 Gy in our patients, doses at which myelotoxicity would have been anticipated.

166Ho-microsphere liver radiotherapy: a preclinical SPECT dosimetry study in the pig.

Liver metastases cause the majority of deaths from colorectal cancer and response to chemotherapy is poor. Intrahepatic arterial 90Y-microspheres may induce tumour regression but the beta-radiation dose is variable and cannot be determined in patients. The 81 keV gamma emission of holmium-166 (166Ho) was used to determine, by single photon emission computed tomographic (SPECT) imaging, the beta-radiation absorbed dose to normal liver in pigs following intrahepatic arterial administration of 166Ho-microspheres. The SPECT system was calibrated with anthropomorphic liver phantoms containing known activity concentrations of 166Ho-chloride. The relationship of SPECT counts to phantom activity concentration was linear with a correlation coefficient of r = 0.996. The SPECT pattern of liver distribution following successive administrations of tracer activities of 166Ho-microspheres was similar. The ratio of initial to total SPECT estimates of mean activity concentration in regions of interest, from which anatomically matched biopsy samples were later obtained and counted in an ionization chamber, showed good correlation (r = 0.924). Prospective SPECT dosimetry performed on a tracer activity of 166Ho-microspheres predicted the total administered activity required to deliver a prescribed radiation absorbed dose of 25 Gy to the liver within an error of +/- 8%. This study demonstrates the feasibility of prospective control of the absorbed radiation dose to the critical normal organ by SPECT dosimetry on a tracer dose of 166Ho-microspheres prior to administration of a therapy dose.

Articular mobility in systemic lupus erythematosus (SLE).

The study was prompted by the suggestion that inflammatory polyarthritis and corticosteroids increase articular mobility. Ninety female patients with systemic lupus erythematosus (SLE) of whom 85 had polyarthritis and at least 75 of whom had received corticosteroid therapy were studied and compared to an equal number of carefully matched controls. The difference between the number of hypermobile patients [6 (7%)] and controls [5 (6%)] was not significant. There was also no significant difference when either the pooled mobility scores or the pooled hand scores of the patients and controls were compared. No significant association between articular mobility and either age at onset of disease, duration of disease or corticosteroid therapy was demonstrated. There was a significant association between deformity and duration of disease (p = 0.04) but not with mobility score. We conclude that SLE patients do not have a hypermobile tendency and therefore that neither SLE nor corticosteroids predispose to increased articular mobility. There is also no association between articular mobility and deformity.