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Biomedical subjects

J R Mekkes

Publications and source records attributed to J R Mekkes.

At least 19 recordsLinked to original sources

[Loss of cranial-nerve function caused by early syphilitic meningitis: the comeback of a pre-war syndrome].

Two men aged 39 and 38 who had had unprotected insertive and receptive anal sexual contact with men are presented: one had paralysis of the right half of his face and the other man had erythematous macules on the palms of his hands and the soles of his feet as well as partial alopecia, earache and progressive loss of hearing in his left ear. The latter one was also HIV-seropositive and on antiretroviral medication. Syphilitic meningitis was diagnosed in both men. The 2 patients recovered after being treated with intravenous benzyl penicillin. Syphilitic meningitis is a complication seen during the early stages of a syphilis infection. Since the introduction of penicillin it has become a rare disease. Early diagnosis is of importance since syphilitic meningitis has irreversible sequelae.

Adult↗

Causes, investigation and treatment of leg ulceration.

Chronic ulceration of the lower leg is a frequent condition, with a prevalence of 3-5% in the population over 65 years of age. The incidence of ulceration is rising as a result of the ageing population and increased risk factors for atherosclerotic occlusion such as smoking, obesity and diabetes. Ulcers can be defined as wounds with a 'full thickness depth' and a 'slow healing tendency'. In general, the slow healing tendency is not simply explained by depth and size, but caused by an underlying pathogenetic factor that needs to be removed to induce healing. The main causes are venous valve insufficiency, lower extremity arterial disease and diabetes. Less frequent conditions are infection, vasculitis, skin malignancies and ulcerating skin diseases such as pyoderma gangrenosum. But even rarer conditions exist, such as the recently discovered combination of vasculitis and hypercoagulability. For a proper treatment of patients with leg ulcers, it is important to be aware of the large differential diagnosis of leg ulceration.

Arterial Occlusive Diseases↗

Acquired arteriovenous malformation induced by pressure: a case report.

Arteriovenous malformations may be congenital or acquired. In the latter case, usually a traumatic injury to the arteries precedes the arteriovenous anastomoses. Two elderly patients presented with large, purple-colored verrucous tumors on the buttocks. Both patients were obese and immobile, and reported repeated bleeding from the lesions after minor trauma. The tumors were soft and could be emptied by applying pressure. Doppler examination revealed arterial pulsations over the lesions. Both cases were diagnosed as pressure-induced arteriovenous malformations. The lesions are assumed to have been caused by tissue damage in the deep subcutis induced by decubitus.

Aged↗

Natural course of physical and chronic urticaria and angioedema in 220 patients.

BACKGROUND: Information about spontaneous remission of chronic urticaria is limited. OBJECTIVE: To investigate the natural course of urticaria, we followed up 220 adults in a prospective study. METHODS: Patients were followed up for 1 to 3 years to evaluate interventions, to detect latent causes, and to study the natural course of urticaria. The diagnosis was made by detailed history-taking as well as laboratory and provocation tests. RESULTS: Thirty-five percent of all patients were free of symptoms after 1 year. In 28.9% of patients, symptoms had decreased. Spontaneous remission occurred in 47.4% of the patients in whom no cause of their urticaria and/or angioedema could be identified and in only 16.4% of the patients with physical urticaria. A cause could be identified in 53.1% of the patients. Thirty-six percent of the patients had idiopathic urticaria. Chronic idiopathic urticaria combined with physical urticaria occurred in 10.9%. CONCLUSION: In general, the prognosis for spontaneous remission is reasonable, with the exception of the subgroup (33.2%) with physical urticaria.

Adolescent↗

Dermal organization in scleroderma: the fast Fourier transform and the laser scatter method objectify fibrosis in nonlesional as well as lesional skin.

Scleroderma, a chronic, progressive disorder, is characterized by dermal fibrosis with collagen bundles orientated parallel to the epidermis. Simple objective parameters to evaluate disease progression and therapies are needed. We describe two methods, the laser scatter method and the fast Fourier transform (FFT), to measure collagen bundle orientation and spacing. Lesional sclerodermic skin (LS), nonlesional sclerodermic skin (nonLS), and control skin (CS) sections were evaluated for orientation ratio using the laser scatter method. The FFT was used to calculate orientation ratio, variation, and spacing of collagen bundles. Parameters were correlated with local and mean skin score measurements, on a scale of 0 (normal) to 3 (severely sclerotic). With both the laser scatter method and the FFT, orientation ratios of LS (respectively, 2.16 +/- 0.33 and 1.83 +/- 0.62) were significantly higher than CS (respectively, 1.70 +/- 0.35 and 1.38 +/- 0.15). NonLS orientation ratios (respectively, 1.92 +/- 0.15 and 1.48 +/- 0.44) were between LS and CS ratios. Orientation variation and bundle spacing of LS (respectively, 57.3 +/- 19.4 and 15.7 +/- 5.6 microm) were significantly reduced compared to CS (respectively, 73.8 +/- 15.0 and 18.9 +/- 1.9 microm). NonLS orientation ratios (respectively, 57.2 +/- 29.0 and 15.6 +/- 6.1 microm) were similar to LS. Bundles in LS are more parallel, show less variation in orientation, and are more densely packed than in CS. There was a linear correlation between mean skin score and orientation ratio. Local skin score was not linearly correlated to orientation ratio. Our findings suggest that nonLS dermis without clinical sclerosis already shows fibrotic characteristics. Both techniques were easy to use and suitable for objectifying dermal fibrosis in scleroderma lesions. FFT is more accurate and reproducible than the laser scatter method and allows simultaneous pathological evaluation of the location of the analyzed tissue sections. Future studies will need to focus on the correlation between clinical disease severity and collagen bundle characteristics.

Adolescent↗

[A questionnaire for patients with chronic urticaria; a diagnostic approach based on structured anamnesis].

In only a minority of chronic urticaria patients an underlying cause or illness can be detected. Previous studies demonstrated that detailed history taking is more important than routine laboratory investigations. To improve the process of history taking, the use of a detailed urticaria questionnaire is highly recommended. By using such a history-based diagnostic approach, the costs of laboratory investigations could be reduced from an average of 538 NLG per patient to 84 NLG per patient. The percentage of patients in whom a cause could be found increased from 29% to 53%. No severe underlying illnesses were missed by using this approach.

Clinical Laboratory Techniques↗

Treatment of patients with systemic sclerosis with extracorporeal photochemotherapy (photopheresis).

BACKGROUND: Effective treatment modalities for systemic sclerosis, a life-threatening and disabling disease, are still lacking. Possible efficacy of photopheresis has been reported in several studies. Because of the complexity of the treatment, placebo-controlled trials are difficult to perform. OBJECTIVE: We investigated the effect of photopheresis on clinical parameters (skin score and internal organ functions), immunologic parameters, and quality of life. METHODS: Nineteen patients with progressive systemic sclerosis of less than 5 years' duration were randomized into 2 groups. One group (group A) received photopheresis for 1 year, the other group (group B) received no treatment at all. After 1 year the groups switched (crossover design). Photopheresis was performed on 2 consecutive days every 4 weeks; the psoralens were administered parenterally. The main outcome parameter was the skin score after 1 year of treatment compared with that of the control group. RESULTS: The average skin score improved with 5.4% (standard error [SE], 20. 8%) in group A and deteriorated with 4.5% (SE, 13.8%) in group B (not significant; P =.71). Before crossover, the average increase in skin score was 5.3% (means of entire group). No change was observed in other clinical parameters. Approximately 1 year after crossover, the skin score reversed to what would have been expected with an average increase of 5.3% per year. There was also no effect on immunologic parameters. Quality of life did not change during treatment. CONCLUSION: We were not able to show that photopheresis, performed as described above, is an effective treatment in systemic sclerosis. The difference in average skin score was statistically and clinically insignificant. Despite the small sample size, we concluded that the magnitude of the observed changes is too small to justify photopheresis as a regular treatment.

Adult↗

The effectiveness of a history-based diagnostic approach in chronic urticaria and angioedema.

OBJECTIVE: To assess the value of extensive laboratory screening for the identification of causes in patients with chronic urticaria and/or angioedema. DESIGN: In a prospective study involving 220 patients, 2 diagnostic strategies were compared: the combination of detailed history taking and limited laboratory investigations vs detailed history taking and extensive laboratory screening. The results of the extensive screening program were initially kept secret from the patients and the physicians. Later, all results were disclosed, and an investigation was undertaken to find out whether this information changed the initial diagnosis. The patients were followed up for 1 year to evaluate the results of interventions and to detect latent causes. SETTING: The study was performed in the outpatient department of a secondary and tertiary care center with institutional practice. PATIENTS: A total of 238 consecutive new patients with chronic urticaria and/or angioedema edema were referred; 18 of them refused participation. One patient was unavailable for follow-up. MAIN OUTCOME MEASURE: The difference in the number of identified causes between both approaches and the nature of the causes that would have been missed by omitting extensive laboratory screening. RESULTS: With a questionnaire and the limited laboratory tests, a cause was found in 45.9% of the patients, compared with 52.7% with the questionnaire and the extended screening program. Except for one parasitic infection, missed diagnoses were mainly adverse reactions to drugs or food detected by standard elimination procedures, not by laboratory investigations. CONCLUSION: Routine laboratory screening did not contribute substantially to the diagnosis of chronic urticaria or to the detection of underlying disorders.

Adolescent↗

Quantitative and objective evaluation of wound debriding properties of collagenase and fibrinolysin/desoxyribonuclease in a necrotic ulcer animal model.

Proteolytic enzymes have been used for wound debridement for many years. The two enzymes most widely used in Europe are fibrinolysin/desoxyribonuclease and collagenase. Despite their frequent use, very few placebo-controlled studies comparing the enzymes with vehiculum only, or with each other, are available. In a specially developed necrotic ulcer animal model, combined with a computer image analysis technique to measure necrotic and total wound surface areas quantitatively, we assessed the wound-cleansing properties of fibrinolysin/DNase oleogel, collagenase ointment, saline-soaked gauze control treatment, and new galenic formulations of collagenase, including placebos. The average relative area of necrotic tissue present in the wound after 1 week was 31% for collagenase ointment and 56% for fibrinolysin/DNAse oleogel (P = 0.0037). Collagenase gel was significantly (P = 0.0007) better in removing necrosis than placebo (gel only). Fibrinolysin/DNAse was not significantly more effective than the three placebo or control treatments (placebo film, placebo gel, saline-soaked gauzes). We conclude that collagenase is a suitable enzyme for wound debridement, but we were not able to detect clinical efficacy of fibrinolysin/DNAse in this model.

Animals↗

Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds.

In diabetic patients, wound healing is impaired. We studied the pathogenesis behind this clinical observation by characterizing the pattern of deposition of extracellular matrix (ECM) molecules and the cellular infiltrate in chronic (>8 wk) diabetic wounds, compared with chronic venous ulcers and an acute wound healing model. Punch biopsies were obtained from the chronic ulcer margins and control samples were collected from upper leg skin 5, 19, 28 d and 12 and 18 mo postwounding (p.w.). T cells, B cells, plasma cells, granulocytes and macrophages, and the ECM molecules fibronectin (FN), chondroitin sulfate (CS), and tenascin (TN) were visualized using immunohistochemical techniques. Expression of FN, CS, and TN was detected in dermal tissue early in normal wound healing (5-19 d p.w.). Abundant staining was seen 3 mo p.w., returning to prewounding levels after 12-18 mo p.w. In the dermis of chronic diabetic and venous ulcers with a duration of 12 mo or more, a prolonged presence of these ECM molecules was noted. Compared with normal wound healing: (i) the CD4/CD8 ratio in chronic wounds was significantly lower (p < 0.0027) due to a relatively lower number of CD4+ T cells; (ii) a significantly higher number of macrophages was present in the edge of both type of chronic ulcers (p < 0.001 versus day 29 p.w.); and (iii) more B cells and plasma cells were detected in both type of chronic wounds compared with any day in the acute wound healing model (p < 0.04 for CD20+ and p < 0.01 for CD79a+ cells). These data indicate that important differences exist in the cellular infiltrate and ECM expression patterns of acute, healing versus chronic wounds, which may be related to the nonhealing status of chronic wounds.

Acute Disease↗

In vitro tissue-digesting properties of krill enzymes compared with fibrinolysin/DNAse, papain and placebo.

Wound debridement, the removal of necrotic tissue, can be achieved with proteolytic enzymes. Recently, a new multi-enzyme preparation, krill enzyme, isolated from Antarctic shrimp-like organisms (Euphausia superba), was reported to possess powerful proteolytic activity towards protein substrates. In this paper, we study the in vitro digestive properties of krill enzymes towards whole tissue, compared with placebo, papain, and fibrinolysin/DNAse. Freshly obtained skin specimens were exposed for 3 days to krill enzymes (3; 0.6 and 0.06 U/ml), papain (120; 60; 6 and 0.6 U/ml), fibrinolysin/DNAse (2.5/1500 E and 1/600 E), and phosphate-buffered saline control solution. Tissue digestion was estimated by measuring wet wt, dry wt, and histological examination. After 72 hr of exposure to 3 U/ml krill enzymes, the dry wt of the specimens was reduced to 2.7% +/- 1.9 (SEM, n = 5), compared with 31.0% +/- 2.7 for placebo, 25.7% +/- 2.5 for 120 U/ml papain, and 24.5% +/- 3.3 for 2.5/1500 E/ml fibrinolysin/DNAse. The differences between krill enzymes and fibrinolysin/DNAse, papain, and control solution were statistically significant (p < 0.007). These data suggest that krill enzymes are more active than other commonly available proteolytic agents used for wound debridement.

Animals↗

Extracorporeal photochemotherapy (photopheresis) induces apoptosis in lymphocytes: a possible mechanism of action of PUVA therapy.

The mechanism of action of psoralen plus UVA (PUVA) and photopheresis is not entirely understood. These therapies are assumed to be immunomodulating partly by gradually decreasing leukocyte viability. We investigated whether this delayed form of cell death was due to apoptosis. Untreated and treated (PUVA exposed) leukocytes obtained from six patients with systemic sclerosis and (untreated) leukocytes from healthy control individuals were studied. Qualitative gel electrophoresis and quantitative in situ nick translation analysis of DNA fragmentation was performed. Apoptosis of the treated cells did occur (gel electrophoresis) after 24 h. At t = 0 h, immediately after exposure to PUVA, there was no evidence of DNA fragmentation in the treated cells. The percentage of treated cells undergoing apoptosis was 20-55% at t = 24 h (in situ nick translation). The untreated leukocytes of the patients and the healthy individuals showed no distinctive rise in apoptotic cells. Apoptosis of the leukocytes after PUVA or photopheresis treatment might be a mechanism of action and might explain the therapeutic response.

Apoptosis↗