Takao Tachibana

Development of the DESIGN‐R with an observational study: An absolute evaluation tool for monitoring pressure ulcer wound healing

DESIGN is a seven‐item (depth, exudates, size, inflammation/infection, granulation, necrosis, and pocket) monitoring scale for pressure ulcers developed in 2002 by the scientific education committee of the Japanese Society of Pressure Ulcers. DESIGN is a very useful tool for chronological monitoring of each pressure ulcer, but a key limitation of this tool is its inability to compare the wound‐healing process among different pressure ulcers in different patients due to a lack of statistical item weighting. Our aim was to weight DESIGN items by statistical analysis and develop a new validated tool to overcome this limitation. Subjects comprised 3,601 patients with pressure ulcers. Patients were followed every week during the study period. To establish the weighting of each item and grade, we estimated the probabilities of wound healing at 12‐month follow‐up using multivariable Coxs regression analysis. Weighting (−β value) for each item in order of the highest rank was: pocket, 2.289; size, 1.573; inflammation/infection, 0.778; granulation tissue, 0.682; exudate, 0.543; and necrotic tissue, 0.529. Based on these findings, a new, validated “DESIGN‐Rating tool” for monitoring the progression of pressure ulcer healing was developed, implying the development of an absolute evaluation tool and clinical indicator to assess the quality of medical care.

Clinical wound assessment using DESIGN‐R total score can predict pressure ulcer healing: Pooled analysis from two multicenter cohort studies

There are few clinical tools with both predictive validity for pressure ulcer healing and availability in broad populations. We evaluated whether the total scores from DESIGN‐R tool could predict pressure ulcer healing. We followed 3,196 patients with pressure ulcers from two multicenter cohort studies until wound healing, patient death, or discharge. Wound severity was evaluated by DESIGN‐R tool from 0 (healed) to 66 (greatest severity). In the multivariate Cox proportional hazard model, higher DESIGN‐R total scores at baseline were associated with lower healing rates (hazard ratio 0.90, 95% confidence interval 0.89–0.92), independent of the patients characteristics, setting types, and wound depth or location. DESIGN‐R had discriminative value for wound healing up to 90 days; the area under the receiver‐operating characteristics curve from univariate analysis was 0.81 for healing within 30 days and 0.74 for healing within 30–90 days. The cutoff points were 9 for healing within 30 days and 18 within 30–90 days (positive and negative predictive value 78.8 and 74.1%; 63.9 and 81.1%, respectively). These points were validated for both superficial and deep ulcers. DESIGN‐R can be a useful tool to predict pressure ulcer healing for a wide range of patient populations, settings, and wound locations.

Oral Contraceptive‐induced Lupus Erythematosus in a Japanese Woman

A case of oral contraceptive‐induced lupus erythematosus (LE) was reported. Erythematous skin lesions were noticed on hypothenor sites of palms and acral sites of pedes. Abnormal laboratory findings included an elevated ESR, CRP and weakly positive anti‐nuclear antibodies. Skin biopsy specimens from involved skin showed Clq deposits at the dermo‐epidermal junction.

Histamine metabolism in the arthus reaction

Histamine metabolism, i.e., concentration of histamine and activities of histamine-degrading enzymes, histamine-N-methyltransferase (HMT), and diamine oxidase (DAO), were examined in the Arthus reaction induced in guinea pig skin. The specific activity of HMT was 44.12 +/- 3.80 pmole/min/mg protein and was about 15 times greater than that of DAO in control specimens. However, HMT activity decreased time dependently to 35% of the control at 3 hr and to 10% 48 hr after the initiation of the reaction. DAO activity increased to 150% till 1 hr followed by a linear decrease to 35% at 6 hr and to 10% at 48 hr. Histamine concentration showed a prominent linear decrease to 15% of the control at 2 hr followed by an increase to about 85% at 6 hr. This biphasic change seemed to be well explained by the dynamic changes in the activities of histamine-degrading enzymes. Such decrease in enzyme activities were not observed in other experimentally induced inflammations including dinitrochlorobenzene allergic and croton oil dermatitis. The addition of tissue extract from the Arthus reaction sites resulted in about 30% inhibition in both of two enzyme activities, suggesting the presence of some inhibitory factor(s) in the reaction sites.

Regulation of the activity of histamine-N-methyltransferase from guinea pig skin by biogenic amines

Histamine-N-methyltransferase, a major histamine-degrading enzyme in the skin, was purified from guinea pig skin about 150-fold. The enzymological characteristics including pH optimum, Km values for substrates, and molecular weight were almost consistent with those reported in the brain. Regulatory mechanism of the enzyme activity by biogenic amines was investigated using the purified specimen. Serotonin, tryptamine, and 5-methoxytryptamine intensely inhibited the activity while tryptophan, melatonin, N-acetylserotonin, tryptophol, and 5-hydroxyindole acetic acid had no significant effects. Dopamine, tyramine, 3-methyltyramine, and phenylethylamine also inhibited the activity while no particular effects were obtained by adrenaline, noradrenaline, tyrosine, and DOPA. Spermidine and cadaverine caused significant but weaker inhibition. These amines acted competitively with respect to histamine, although varying manners were observed with respect to S-adenosyl-L-methionine. From these results, it was concluded that the enzyme activity was inhibited by such compounds in which a certain chemical structure, CH2-CH2-NH2 group neighboring the hydrophobic group, was contained. A possible mechanism of inhibition by the amines is postulated, and possible roles of such compounds in the inflammation by impairing the histamine metabolism is discussed.

Focal dermal hypoplasia (Goltz syndrome) associated with multiple giant papillomas

We report a case of focal dermal hypoplasia (FDH) with multiple giant papillomas on nonperimucosal areas. The patient had had cribriform hyperpigmented and depigmented plaques on the trunk and extremities since birth. There were also hypoplastic skin lesions on the right arm, left elbow and right thigh. The multiple giant papillomas began to appear. when she was 22 years old, on the trunk and extremities. Cryotherapy was effective in controlling them.

Mast cells and histamine metabolism in skin lesions from MRL/MP-lpr/lpr mice.

It is likely that mast cell and histamine metabolism are involved in autoimmune tissue injury such as cutaneous lupus erythematosus (LE) because different histamine receptors can regulate Th1 and Th2 cells. In order to verify the role of the axis of mast cell-histamine metabolism-histamine receptor, the autoimmune mouse has been investigated. The MRL/Mp-lpr/lpr (MRL/lpr) mouse is a good model for the spontaneous development of skin lesions similar to those seen in human LE. In skin lesions from MRL/l mice, there are many infiltrating T cells and mast cells in the dermis and impaired histamine metabolism, in which the low activity of histamine-N-methyltransferase and the related prolonged effects of histamine in the skin tissue seem to play a definite pathological role in the development of spontaneous lupus-like eruptions. The expression of H2R on the mast cell decreases within these skin lesions at 5 months of age. It is interesting that the activity of HMT runs in parallel with the expression of H2R over the time course of the skin changes in MRL/l mice, but the relationship between these two observations remains obscure. The accumulation of mast cells expressing H2R and prolonged effects of histamine may occur to regulate the production of Th1 and Th2 cytokines in the skin lesions of MRL/l mice.

Impaired histamine metabolism in the Arthus reaction induced in guinea-pig skin.

SummaryThe activities of two histamine-metabolizing enzymes, histamine-N-methyltransferase (HMT) and diamine oxidase (DAO), were examined in various types of experimentally induced cutaneous inflammations in guinea pigs. In intact guinea-pig skin, the specific activities of HMT and DAO were 24.8±1.7 pmol/min per milligram of protein or 0.930±0.097 pmol/min per milligram of the wet weight of skin specimen, and 6.0±0.7 pmol/min per milligram of protein or 0.189±0.011 pmol/min per milligram of the wet weight, respectively. Both enzyme activities were markedly reduced in skin lesions of the Arthus reaction (P<0.005), while those in dinitro-chlorobenzene allergic dermatitis, croton-oil dermatitis, and the intact areas in Arthus-reaction-induced aminals were almost within the normal limits. The activity of HMT decreased linearly with time from the onset of the Arthus reaction, reaching about 20% of the control activity at 48 h; the activity of DAO decreased even from the early stages of the reaction, and this decrease continued throughout first 48 h of the reaction. These results suggest that impaired histamine metabolism in the skin lesions of the reaction plays a distinct role in the formation and development of the Arthus reaction.

Impaired histamine metabolism in human erythematous dermatoses.

The specific activities of histamine‐N‐methyltransferase, the only enzyme to degrade histamine in human skin, were examined in 7 specimens from normal skin, 42 from erythema multiforme, erythema nodosum, erythema annulare or drug‐induced erythema and 12 from psoriasis or eczema. The enzyme activity was 3.45 ± 0.17 pmol/min/mg protein (mean ± S.E., n=7) in normal skin. The activities were significantly lower in 24 out of 30 freshly active lesional sites of erythematous dermatoses (lower than 2 S.D. from the mean in normal skin), while the activities in the central clearing areas were rather higher than those in the freshly active lesions. No significant changes were seen in the lesional skin of psoriasis or eczema. Decreased histamine‐degrading enzyme activity in the freshly active lesions of erythematous dermatoses may suggest the long lasting effect of the amine that was released in the lesions. In spite of the different clinical figures and multiplicity of etiologies, decreased histamine‐N‐methyltransferase activity was quite commonly observed, suggesting a similarity in the pathomechanisms of these dermatoses.

Serum albumin level is a limited nutritional marker for predicting wound healing in patients with pressure ulcer: two multicenter prospective cohort studies.

BACKGROUND & AIMS We aimed to investigate the predictive validity of serum albumin for pressure ulcer healing, according to patient condition and wound characteristics. METHODS This study was a secondary analysis of pooled data from two multicentre cohort studies undertaken in 2005 and 2007. All adult patients with pressure ulcer were included and were tracked until wound healing or discharge from care. Baseline serum albumin data were obtained from medical charts. RESULTS A total of 2530 patients were analyzed. By multivariate Cox proportional hazards analysis, higher serum albumin level was associated with wound healing of only superficial pressure ulcers for patients in acute/postoperative conditions (hazard ratio 1.29, 95% confidence interval 1.13-1.46) and the cutoff point was 24/25 g/L. However, the addition of serum albumin level to other factors resulted in little increase in the ability to predict wound healing as measured by the overall C-statistics. For patients in chronic/palliative conditions, serum albumin level as the continuous variable was not significantly associated with ulcer healing. CONCLUSIONS The addition of serum albumin marker may not have much advantage to predict pressure ulcer healing although its level can be associated with ulcer healing, depending on patient condition and wound depth.