Biomedical subjects
Publications and source records attributed to P Humbert.
Since 1967, about 40 cases of digital necrosis associated with neoplasia have been reported. We report a new case of digital necrosis associated with an ovarian carcinoma and with a lupus-like syndrome. Immunologic cross-reactivity to tumoral antigen could explain the lupus-like syndrome.
UNLABELLED: IgA system has been poorly studied in patients with atopic dermatitis (AD). Previous studies have showed that a transient serum IgA deficiency in infancy could lead to atopic disease. In addition, decrease in salivary IgA has been demonstrated in patients with AD. The purpose of our work was to study the IgA system both in serum saliva in patient with AD. PATIENTS AND METHOD: We conducted a controlled prospective study from January 1994 to May 1996. 46 patients with AD and 52 healthy volunteers matched for sex and age were included. Atopic patients fulfilled at least three major and three minor features defined by Hanifin and Rajka. None above atopic criteria were present in the control group. Saliva was collected using a small cylinder of a cotton-wool-like substance (Salivette) kept in the buccal fold. Serum and saliva samples were assayed for IgA using standard nephelometric method and time-resolved immunofluorometric assay. Secretory IgA were assayed by a sandwich-type enzyme linked immunosorbent assay. Blood eosinophils and serum IgE were also evaluated. RESULTS: IgA and secretory IgA were detected in all serum and saliva collected. No statistically significant difference were observed in serum or in saliva for both IgA and secretory IgA between patients with AD and controls. As expected, blood eosinophils and serum IgE were significantly increased in patients with AD. DISCUSSION: None patients (atopic or control) exhibited IgA deficiency. Although no statistically significant, a trend to higher concentrations of serum and salivary IgA was observed in patients with AD suggesting a stimulation of mucosa-associated lymphoid tissue in these patients.
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8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP) and 4,5',8-trimethylpsoralen (TMP) are commonly used in PUVA therapy [psoralen (P) + ultraviolet light A (UVA) irradiation] to treat skin diseases such as psoriasis and vitiligo. In order to predict the choice of the suitable drug(s) for topical applications, with appropriate dosage, percutaneous permeation of the psoralens, in connection with their solubilities and partition coefficients in an octanol/water system, were investigated. The percutaneous penetration experiments were accomplished by the deposit of ethanolic psoralen solution onto human skin and epidermis fragments mounted on Franz cells. Six cells were employed for each psoralen solution and for the whole skin layer as well as for the epidermis. The diffused psoralens in the receptor solution (1.4%, of human serum albumin) were quantified by using high performance liquid chromatography. The solubilities and the partition coefficients (PC) were carried out in an octanol/water system, in triplicate by using spectrofluorimetry. The results demonstrated that cumulated permeated quantities (ng/cm2) over 24 h, across the whole skin and the epidermis were in the following order for the three psoralens: 8-MOP > 5-MOP > TMP. The lipophilicity, expressed via the log PC, was as follows: 1.93 +/- 0.01 (8-MOP), 2.00 +/- 0.01 (5-MOP) and 3.14 +/- 0.01 (TMP). It was inversely correlated with cumulated penetrated amounts over 24 h in both whole skin and epidermis. From these results, TMP could be predicted as the most convenient psoralen for topical applications, because of its weak penetrability. Considering the relationship between psoralens lipophilicity and permeation, only 5-MOP and 8-MOP could be used, topically or orally, especially in the case of generalised skin disorders.
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In medicine, psoriasis and vitiligo are most often treated with PUVA therapy (psoralen plus ultraviolet A). The determination of psoralen in patients' blood is necessary, as it is admitted that the therapeutic efficiency depends on drug concentration in patients' serum. The amount of UVA to administer is inversely proportional to serum peak concentration. High-performance liquid chromatography (HPLC) and gas chromatography are the most employed methods for determining psoralens in patients' serum. The 2 techniques are precise and very sensitive, but time consuming. The aim of this paper is to propose a suitable method which is rapid and simple. It is a spectrofluorimetric technique for 5-methoxypsoralen (5-MOP) determination in the serum of patients treated with PUVA therapy. 5-MOP extraction was carried out with an heptane/dichloromethane mixture (4/1; v/v), according to the Stolk method (1980). A calibration curve (CC) was plotted from 5-MOP concentrations (range 50, 100, 200, 300, 400, 500 ng/ml). The CC was linear with a good coefficient of correlation: r = 0.9971, and a suitable coefficient of variation (CV) of 7.0%. The recovery of the method ranged from 85.3 +/- 4.2 to 108 +/- 4.1%. The assay precision gave a CV ranging from 0.10 to 6.90%, with an error inferior to +/-10%. The method did not reveal any interference from serum components on the 5-MOP emission wavelength. The limit of detection of 5-MOP was 15 ng/ml. The proposed procedure was proved to be appropriate for a rapid determination of 5-MOP in patients' serum. This technique could also be employed for other psoralens used in PUVA therapy (e.g., 8-methoxypsoralen).
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Alveolar echinococcosis is a rare parasitic disease caused by the intrahepatic growth of Echinococcus multilocularis larvae. Secondary localizations can be observed; pulmonary metastases are the most frequent and are observed in 22% of patients. Other extrahepatic localizations are less frequent. We describe two patients with abdominal skin involvement. To our knowledge, this has never before been reported. In both patients, the liver lesion was located in the left lobe, and larvae probably spread to the skin via the falciform ligament. In one patient albendazole therapy was effective.
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Despite data favouring a role of dietary fat in colonic carcinogenesis, no study has focused on tissue n3 and n6 fatty acid (FA) status in human colon adenoma-carcinoma sequence. Thus, FA profile was measured in plasma phospholipids of patients with colorectal cancer (n = 22), sporadic adenoma (n = 27), and normal colon (n = 12) (control group). Additionally, mucosal FAs were assessed in both diseased and normal mucosa of cancer (n = 15) and adenoma (n = 21) patients, and from normal mucosa of controls (n = 8). There were no differences in FA profile of both plasma phospholipids and normal mucosa, between adenoma and control patients. There were considerable differences, however, in FAs between diseased and paired normal mucosa of adenoma patients, with increases of linoleic (p = 0.02), dihomogammalinolenic (p = 0.014), and eicosapentaenoic (p = 0.012) acids, and decreases of alpha linolenic (p = 0.001) and arachidonic (p = 0.02) acids in diseased mucosa. A stepwise reduction of eicosapentaenoic acid concentrations in diseased mucosa from benign adenoma to the most advanced colon cancer was seen (p = 0.009). Cancer patients showed lower alpha linolenate (p = 0.002) and higher dihomogammalinolenate (p = 0.003) in diseased than in paired normal mucosa. In conclusion changes in tissue n3 and n6 FA status might participate in the early phases of the human colorectal carcinogenesis.
Copper and zinc percutaneous absorptions were assessed in vitro using sliced human skin and both petrolatum and hydrophilic gels as vehicles. Applied quantities were largely in excess for the duration of the experiment (72 h). The absorption of sulphates and chlorides was compared. The cumulated amount recovered in receptor fluid was below 50 micrograms/cm2. The apparent permeability constant values kept in the range of 10(-6) cm h-1, except for ZnCl2 in gel vehicle (2.9 10(-5) cm h-1). With the exception of CuCl2 in gel vehicle, chlorides gave higher absorption rates than sulphates. This can be related to the higher octanol-water partition coefficient of chlorides. Storage within the epidermis was found to be equal to or greater than, and within the dermis equal to or lower than the 72 hour cumulative amount in receptor fluid. No difference was found in this respect between copper an d zinc. This work confirms the poor absorption of electrolytes through normal human skin, whatever the vehicle used.
Percutaneous absorption and cutaneous bioavailability of zinc and copper from zinc 2-pyrrolidone 5-carboxylate (ZnPC), zinc oxide (ZnO), zinc sulfate (ZnSO4), copper 2-pyrrolidone 5-carboxylate (CuPC) and copper sulfate (CuSO4) were compared using 5 formulations (3 emulsions and 2 ointments) that were applied topically on human skin in vitro. After application for 72 h, percutaneous absorption of zinc from ointments containing ZnO and ZnSO4 was found to be lower than that from a ZnPC-containing emulsion (0.36 and 0.34 versus 1.60% of applied dose). In the case of copper, the flux after a 72-hour treatment period showed that there had been minimal release from CuPC- and CuSO4-containing formulations (approximately 5 ng/cm2/h). All formulations used in this study effected an increase in zinc and copper concentrations in whole skin and epidermis. Bioequivalence of the 5 formulations based on pharmacokinetic results was assessed, and salt and vehicle effects were discussed.
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BACKGROUND/AIM: Therapeutic regimens with intravenous (i.v.) cyclosporine followed by oral cyclosporine maintenance therapy reduce the need for immediate surgery in steroid-refractory severe ulcerative colitis, but the short-term colectomy rate is still as high as 70%. We report our experience with long-term azathioprine maintenance therapy in a small series of ulcerative colitis patients with i.v. cyclosporine-induced remission. METHODS AND RESULTS: Twelve of thirteen patients with severe ulcerative colitis refractory to i.v. prednisone (1 mg/kg/day for at least 10 days) went into remission after adding i.v. cyclosporine (4 mg/kg/day) and are the subjects of this report. After a discouraging initial experience with oral cyclosporine plus mesalazine as maintenance therapy in the first four patients, we treated the following patients with azathioprine plus mesalazine starting immediately after response to i.v. cyclosporine was obtained. Overall, only 1 of 10 patients treated with azathioprine relapsed after a mean follow-up of 16.3 months (range: 6-48). Moreover, this relapse probably occurred when the drug was still not therapeutically active because, after reinducing remission with oral prednisone, the patient remained symptomless on azathioprine. Steroids could be discontinued in all patients. CONCLUSIONS: The relapse rate on maintenance therapy with azathioprine (10%) is a figure considerably lower than that previously reported with oral cyclosporine. This promising experience should be confirmed in randomized controlled trials.
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