Frederik Grønhøj Larsen

Clinical and dermatoscopic diagnosis of malignant melanoma. Assessed by expert and non-expert groups.

We investigated the nosographic and diagnostic probabilities and likelihood ratios of dermatoscopy in order to evaluate the methods role in decision-making regarding melanoma. Clinical slides and dermatoscopic photos were obtained from 232 patients referred for dermatoscopy. Four dermatoscopy experts and 5 non-experts assessed the slides. Diagnoses were compared with histopathology. Sensitivity of the clinical assessments was 0.78 vs. 0.69 (experts vs. non-experts), sensitivity of dermatoscopy assessment was 0.83 vs. 0.69 (p = 0.04). The expert group demonstrated increased specificity (from 0.89 to 0.94) when applying dermatoscopy compared with clinical assessment alone (p=0.03). Positive likelihood ratios were doubled in the expert group and the negative likelihood ratios improved 25% with dermatoscopy compared with clinical assessment.

The dermatoscopic ABCD rule does not improve diagnostic accuracy of malignant melanoma

The dermatoscopic ABCD rule has been suggested to improve diagnostic performance regarding cutaneous malignant melanoma. Using this rule, a total dermatoscopy score is calculated from the presence of various dermatoscopic elements. A total dermatoscopy score above 4.75 signifies possible and 5.45 probable melanoma. We compared the diagnostic accuracy of dermatoscopy with and without the use of the ABCD rule. Furthermore, receiver operating characteristic analysis was performed for the ABCD rule. The area under the receiver operating characteristic curve was 0.854 (range 0.777-0.906) demonstrating that in 85.4% of the cases, cutaneous malignant melanomas were rated higher than the non-melanoma skin lesions. Sensitivity for the melanoma diagnosis was higher for simple dermatoscopy than when the ABCD rule was used (p<0.05). There was no difference in specificity when a total dermatoscopy score of 4.75 was used as cut-off point, but specificity was lower for simple dermatoscopy than when the total dermatoscopy score of 5.45 was used. Diagnostic accuracy was higher for simple dermatoscopy than for the ABCD rule (p<0.01). In conclusion, the dermatoscopic ABCD rule was not superior to simple dermatoscopy, and fewer malignant melanomas were identified with this rule.

Pharmacokinetics and therapeutic efficacy of retinoids in skin diseases.

SummaryThe retinoids are a class of compounds that includes the natural forms and synthetic analogues of vitamin A. Isotretinoin, often referred to as a first generation retinoid, may be of considerable benefit to patients with severe, recalcitrant acne. Etretinate and acitretin, 2 aromatic compounds representing the second generation, have found their major success in the treatment of psoriasis, particularly in combination with more traditional therapies. Retinoid therapy is associated with a distinctive adverse effect profile typical of hypervitaminosis A; thus, it is especially important that fertile women undergoing retinoid therapy adhere to a contraceptive regimen. These drugs are extensively metabolised and only traces of unchanged drugs are eliminated in urine. The terminal elimination half-lives of isotretinoin, etretinate and acitretin after long term treatment are up to 20h, 120 days and 48h, respectively. Because of lack of definite correlation between plasma concentration and desired pharmacological effects, in conjunction with the very pronounced inter- and intraindividual variation in systemic availability (15 to 90%) after oral administration of these drugs, initial dosages in individual patients can only be roughly judged on the basis of the general pharmacokinetics of the agents. Later dosage adjustments should be made on the basis of monitoring of both plasma drug (and possible metabolite) concentrations, and the efficacy and tolerability of the drugs.

ETAF/Interleukin-1 and epidermal lymphocyte chemotactic factor in epidermis overlying an irritant patch test

We have previously demonstrated that the epidermal content of the lymphocyte activating peptide ETAF/IL‐1 and lymphocyte chemotactic factor (ELCF) increases during the development of a cellmediated immune reaction, represented either by the tuberculin skin reaction or by a positive patch test in patients with contact allergy. The present study describes the epidermal content of these mediators during an irritant patch test reaction. The results show that ELCF, but not ETAF/IL‐1, is significantly increased in the epidermis of an irritant patch test with 3% SLS or 5% croton oil, irrespective of the intensity of the clinical patch test reaction. We observed that simple occlusion of epidermis did not induce ELCF activity in healthy persons, whereas patients with previous or current eczema had a significant release of ELCF following such occlusion. These results seem to indicate that there exist important functional differences between allergic and irritant patch test reactions with respect to the presence of lymphocyte activating signals in epidermis.

Epidermis and lymphocyte interactions during a tuberculin skin reaction

SummaryForty-one persons were tested for tuberculin skin reactivity. Epidermal cells (ECs) were isolated from the tuberculin reaction and from a contra lateral, non injected skin area. We found a significant increase of epidermal thymocyte activating factor (ETAF) in epidermis overlying a positive tuberculin reaction together with an increase of OKT6 and class II (HLA-DR) positive cells. Allogeneic lymphocytes proliferated significantly more when mixed with ECs from a positive tuberculin skin test. Injection of tuberculin per se or a negative reaction did not induce similar changes. The described model seems useful for functional studies of ECs and lymphocytes in patients with contact dermatitis.Forty-one persons were tested for tuberculin skin reactivity. Epidermal cells (ECs) were isolated from the tuberculin reaction and from a contra lateral, non injected skin area. We found a significant increase of epidermal thymocyte activating factor (ETAF) in epidermis overlying a positive tuberculin reaction together with an increase of OKT6 and class II (HLA-DR) positive cells. Allogeneic lymphocytes proliferated significantly more when mixed with ECs from a positive tuberculin skin test. Injection of tuberculin per se or a negative reaction did not induce similar changes. The described model seems useful for functional studies of ECs and lymphocytes in patients with contact dermatitis.

Necrotizing Soft Tissue Infection of the Glans Penis due to Atypical Candida Species Complicated with Fournier's Gangrene

Sir, Necrotizing soft tissue infections are characterized by tissue necrosis, ranging from superficial dermal involvexad ment to deeper involvement of the fascia and muscle layers. Between 500 and 1500 cases are reported annually in the USA, and the mortality ranges from 24–34%. Most infections are polybacterial and are usually caused by a mix of aerobes and anaerobes (1). In contrast, necrotizing soft tissue infections due to fungi are very rare (2–4). We describe here a case of superficial necrosis of the glans penis due to Candida glabrata and C. tropicalis complicated with conventio nal Fournier’s gangrene of the scrotum in an immunosuppressed patient.

Estimation of stability of [3H]-ouabain binding site concentration in rat and human skeletal muscle post mortem

The post mortem stability of the [3H]-ouabain binding site concentration and 3-O-methylfluorescein phosphatase (MFPase) activity was evaluated in rat skeletal muscle. As compared with the values measured in fresh tissue, the [3H]-ouabain binding site concentration in rat soleus muscle only dropped by around 1% per hour post mortem and a significant decrease was only seen after 12 h (15%, p less than 0.02). The 3-O-MFPase activity in rat gastrocnemius muscle showed a similar decrease. After 4 days, both parameters had dropped by 65% (p less than 0.001). In contrast, when intact fresh rat soleus muscles were incubated in Krebs-Ringer bicarbonate buffer at 20 degrees C for 4 days no significant decrease was seen in the [3H]-ouabain binding site concentration. In 10 human subjects the concentration of [3H]-ouabain binding sites was measured in specimens of the vastus lateralis muscle obtained within half an hour and at 6 and 12 h post mortem. The relative decrease after 6 h was insignificant (8%, p less than 0.30), whereas it was significant after 12 h (29%, p less than 0.005). These results have shown that the [3H]-ouabain binding sites in human skeletal muscle are resistant to post mortem degradation during the first 6 h after death. This makes it possible to perform measurements post mortem of the [3H]-ouabain binding site concentration in human skeletal muscle.

Multiple cobinding of two ligands to serum albumin: A stoichiometric description of binding equilibria

Binding equilibria for simultaneous binding of several molecules of two anionic ligands, sulfamethizole/warfarin in one series and sulfamethizole/diflunisal in another, to human serum albumin were studied by equilibrium dialysis. It was found that Klotzs stepwise binding equilibrium concept, extended to cover interaction of two ligands with one carrier, could be used for a quantitative description of binding equilibria. Reciprocity of ligand effects was established at all levels. Heterotropic anticooperativity was present among these pairs of ligands. The experiments were supplemented with observations of albumin binding equilibria for traces of warfarin in the presence of varying amount of oleate, up to 6 mol/mol albumin, by measuring dialysis rates for unbound warfarin. Binding of warfarin to albumin is enhanced upon binding of oleate up to 4 mol/mol albumin, and decreases at higher oleate concentrations. Using stoichiometric (stepwise) binding constants for oleate previously published by Ashbrook et al. [(1975) J. Biol. Chem. 250, 2333-2338], the reverse effect, of warfarin on binding of oleate, was calculated. Simultaneous binding of these ligands to albumin could be described according to the stoichiometric principles as used above for sulfamethizole/warfarin and sulfamethizole/diflunisal.

Warfarin—sulfinpyrazone interaction on binding to human serum albumin

Sulfinpyrazone displacement of warfarin from human serum albumin was studied in‐vitro. At low sulfinpyrazone concentrations one molecule of warfarin is displaced on binding by one molecule of sulfinpyrazone. Clinical plasma concentrations of sulfinpyrazone are, however, too low to cause significant displacement.