J. K. Kristensen

The effect of leucotriene C4 and D4 on cutaneous blood flow in humans

Abstract Using a laser-Doppler-flowmeter the microvascular response to LTC 4 and LTD 4 was measured. Intradermal injection of 1 Ug LTC 4 and LTD 4 caused an increase in the microvascular cutaneous bloodflow. The increase in flow was equal to that caused by histamine in equimolar amounts. Blocking the triple-response did not change the response. The values measured after injection of histamine and leucotrienes were about 10–15 times the values found in undisturbed skin and represents probably a maximally dilated vascular bed. Injection of the leucotrienes caused a slight sensation of pain.

Elevated plasma levels of vascular endothelial growth factor and plasminogen activator inhibitor-1 decrease during improvement of psoriasis

Abstract.Objective and Design: An evaluation of angiogenesis related molecules during open treatment of psoriasis.¶Materials and Subjects: Plasma samples and skin biopsies from 16 patients with psoriasis and plasma samples from 13 healthy controls.¶Treatment: Ranitidine 300 mg orally twice daily for 6 months.¶Methods: Vascular endothelial growth factor (VEGF) and plasminogen activator inhibitor-1 (PAI-1) were determined by ELISA methods in plasma collected from the patients before treatment and after 1, 3 and 6 months. Vessel counts were performed in biopsies from affected skin areas taken before treatment and after 3 and 6 months. The results were compared to simultaneous PASI scores.¶Results: Pre-treatment plasma levels of VEGF and PAI-1 were significantly elevated in patients compared with levels in healthy persons (p = 0.02 and p = 0.04, respectively). The plasma levels decreased significantly during treatment (p = 0.03 and p = 0.01, respectively), and the decrease in combined levels correlated with the decrease in PASI score. However, the vessel density in affected skin did not change during treatment.¶Conclusions: Increased pre-treatment levels of VEGF and PAI-1 and decrease during improvement of the disease suggest that the two molecules may play a role in pathogenesis of psoriasis.

Scabies and Pyoderma in Lilongwe, Malawi. Prevalence and seasonal fluctuation.

Abstract: From January 1988 to June 1989, data were collected daily on the patients who were seen at the Dermatology Clinic attached to the Kamuzu Central Hospital, Lilongwe, Malawi. Cases were diagnosed and patients were treated under the supervision of a dermatologist. A total of 34,002 patients were seen during the study period. Of these patients, 15,526 (45.7%) were children and 18,476 (54.3%) were adults. The prevalence of scabies was 40.4% in children and 31.6% in adults, whereas the prevalence of impetigo/bacterial skin infections was 26% in children and 10.4% in adults. Based on data accumulated for periods of 1 month, the incidence rate of scabies was highest during the cold, dry season (May‐November) and the incidence rate of skin infection was highest during the hot, rainy season (December‐April). Since the patients who were studied lived predominantly in rural settings, an explanation for the higher incidence rate of scabies during the cold season could be close body contact resulting from the overcrowding within the houses. The reason for the increase in the incidence rate of pyoderma during the rainy season might be linked to deficiencies in hygienic precautions. A community‐based intervention strategy with children as its target population is proposed to combat these diseases.

Studies on mast cells and histamine release in psoriasis: the effect of ranitidine.

The purpose of this study was to investigate histamine and skin mast cells in psoriasis before and during 6 months of treatment with high-dose ranitidine. Sixteen psoriasis patients, presenting a mean PASI score of 15.4, were compared with 13 age- and sex-matched healthy controls. Resting extracellular skin levels of histamine and histamine release to mast cell secretagogues, as measured by the microdialysis technique, were increased in involved psoriasis skin compared to normal skin in the controls. Plasma histamine, but not basophil histamine release, was significantly increased in the patients. Mast cells and lymphocytes were significantly increased in numbers in involved versus non-involved skin in the patients, the lymphocytes being predominantly T-lymphocytes expressing HLA-DR activation. During 6 months of ranitidine treatment, mean PASI score of 15.4 decreased to 5.8. The lymphocyte infiltration, but not mast cell numbers, was significantly reduced during treatment, and histamine release to mast cell secretagogues was normalized. These observations suggest that skin mast cells in active psoriasis are functionally hyperreactive. The biochemical findings together with the clinical effect of ranitidine indicate that histamine may be involved in the pathophysiology of psoriasis.

Systemic high-dose ranitidine in the treatment of psoriasis: an open prospective clinical trial

We report the results of an open, prospective study on the efficacy of systemic ranitidine in the treatment of psoriasis. Twenty patients suffering from moderate to severe psoriasis were included in the study. The median pretreatment PASI score was 15·7 (range 6·0‐24·7). The patients were treated with oral ranitidine 300 mg twice a day for 6 months; no other medication was allowed during the study period. Eighteen patients completed the study. The median PASI score was reduced from 15·7 to 14·5. 9·1 and 5·7. after 1, 3 and 6 months of treatment, respectively (P<0·00001). A significant reduction in PASI score was evident at 3 months of treatment. A mild to moderate deterioration occurred in 15 patients within the first month of treatment, but this was followed by improvement during prolonged treatment in most patients. No other clinical and/or biochemical side‐effects were observed. Eight patients continued therapy with ranitidine after the study was completed, and none of these patients relapsed during a follow‐up period of 12–18 months. The results of the present study suggest that ranitidine may be a beneficial and safe treatment for psoriasis. In addition, high‐dose, long‐term ranitidine treatment appears to be free from severe adverse effects.

Lower leg subcutaneous blood flow during walking and passive dependency in chronic venous insufficiency

The blood flow in the subcutaneous adipose tissue of the lower leg of eight normal subjects and 19 patients with chronic venous insufficiency was measured. The 133Xe‐washout technique was used with portable CdT1(C1) detectors and a data storage unit. Only those patients with ulcers and a systolic blood pressure at the toe of ≥ 60 mm were investigated.

Time-course of corticosteroid-induced blood flow reduction in normal cutaneous tissue—quantitative measurements during 72 h of treatment

In eight healthy individuals, the skin fold between the thumb and the forefinger was treated with 0·05% clobetasol propionate ointment under a hydrocolloid occlusive dressing. Using the atraumatic epieutaneous 133Xe wash‐out technique on the outer 2 mm of the skin fold, covering the rest of the hand with a lead shield, we were able to monitor cutaneous blood flow. Blood flow was measured after 0, 10, 24, 48 and 72 h of treatment. During the first 10 h of treatment no significant change in blood flow was observed. However, compared to untreated tissue, cutaneous blood flow decreased significantly after a 24‐h period (P < 0·05). Furthermore a significant blood flow reduction from 0–48 (P < 0·02) and from 0–72 h (P < 0·01) was observed. Placebo did not decrease cutaneous blood flow, but a minor increase was demonstrated. The results of the present work demonstrate a long‐lasting blood flow reducing effect of topical corticosteroid in normal human cutaneous tissue.

Selection of patients for psoriasis clinical trials: a survey of the recent dermatological literature

Reports of 62 psoriasis clinical trials listed in the Cumulated Index Medicos for the years 1988 and 1989 and published only in leading dermatological journals were evaluated for different elements of research methodology concerned with the recruitment of subjects. The evaluation included items such as eligibility criteria, the sampling process, ethical considerations and sample size calculation. Major weaknesses in the description of all aspects of the recruitment procedure were demonstrated. For example, a quantitative disease activity criterion at entry was mentioned in 15% of the studies, consecutive patients were included in 5% of the trials, sufficient information on ethical approval was given in 16% of the studies, and a pre-study sample size calculation was not mentioned in any of the trials.

The effect of leukotrienes C4 and D4 on microcirculatory flow in humans

By quantifying the flare response, leukotrienes LTC4 and LTD4 were shown to increase the microcirculatory flow in a sigmoidal dose‐response relation over the dose‐range of 6‐25‐800 pmol. LTD4 was found to be more potent than LTC4 after 5 min, but not after 15 min, as estimated by this method. Laser‐Doppler flowmeter studies confirmed that LTD4 is a more potent vasodilator than LTC4.

Coexistence of obstructive arterial disease and chronic venous stasis in leg ulcer patients

Ninety‐four consecutive patients with lower leg stasis ulcers (LSU) were examined for coexistence of arterial occlusive disease. The average age of the patients was 77 years. Two‐thirds of the patients were women. Eleven of the patients had diabetes mellitus. Systolic arm, ankle and toe blood pressures were measured. Indices of ankle/arm (AI) and toe/arm pressure (TI) were calculated. In about half of the patients obstructive leg artery disease was found, defined as an AI of less than 0.9. Fifteen patients were at risk from developing gangrene, having a TI lower than 014. Surprisingly, in the non‐diabetics there was no significant difference between the blood pressure in ulcerated and non‐ulcerated legs. In the diabetics there was a significant difference between ulcerated and non‐ulcerated legs (P<0.05). The TI of the diabetics was significantly lower than that of the non‐diabetics (P<0.05). Our study suggests that patients with obvious stasis leg ulcers should be carefully examined for coexisting leg arterial disease.