Inadequate dietary intake but not renal tubular acidosis is associated with bone demineralization in primary biliary cirrhosis.

BACKGROUND: Metabolic bone disease associated with primary biliary cirrhosis (PBC) is inadequately characterized. Renal tubular acidosis (RTA) may lead to bone loss through chronic mobilization of skeletal calcium salts to buffer increased acid load. AIM: To evaluate the prevalence of RTA in PBC and establish the relationships among bone mineral density (BMD), renal function and nutritional status. METHODS: We enrolled 69 female patients with compensated PBC and 35 control patients with chronic hepatitis C. RTA was searched in all patients, and 24-h dietary recalls were collected at enrolment. BMD was measured by dual-energy X-ray absorptiometry at the femur neck, lumbar spine and radius ultradistalis sites. RESULTS: No patients received a diagnosis of RTA. BMD values (Z-scores) showed only little deviation from normal population with no difference between PBC and controls. Osteopoenic PBC patients (T-score < 1) showed significantly lower daily phosphorus intake [median: 672 (288-1374) vs. 921 (253-1923) mg/day; P = 0.037], with a trend towards lower caloric intake than their nonosteopoenic counterparts. CONCLUSIONS: Renal tubular acidosis is uncommon in compensated PBC. Cholestasis is not associated with an increased risk of bone demineralization. Inadequate dietary intake may be a preventable factor contributing to bone loss in PBC.

Kinetics and dose-response of photosensitivity in cream psoralen plus ultraviolet A photochemotherapy: comparative in vivo studies after topical application of three standard preparations.

BACKGROUND: Topical photochemotherapy with bath psoralen plus ultraviolet (UV) A irradiation (PUVA) has been developed to reduce possible side-effects of oral PUVA therapy. Although the efficacy of bath PUVA therapy appears to be similar to oral PUVA therapy, provision of bathing facilities has obvious economic, logistic and sanitary implications. Cream PUVA therapy has recently been developed as a variation of topical PUVA. OBJECTIVES: To understand the photobiological effects and to increase the safety and effectiveness of this novel topical PUVA therapy, we assessed the kinetics and dose-response of phototoxicity of 8-methoxypsoralen (8-MOP) cream in order to develop a treatment schedule for this treatment option. METHODS: Ninety-eight patients (63 men and 35 women) undergoing cream PUVA therapy were studied. The phototoxic properties of topically applied 8-MOP in three different water-in-oil creams as vehicles were assessed. In a dose-response study, four concentrations of 8-MOP cream (0.0006-0.005%) were used for determination of the minimal phototoxic dose (MPD). The kinetics of photosensitization were tested by determination of MPDs after different application times of 8-MOP cream (10, 20, 30 and 60 min). The persistence of phototoxicity was assessed by UVA exposure at defined time intervals after application of 8-MOP cream (0, 30, 60 and 120 min). RESULTS: The concentration required to produce sufficient but not undue photosensitization of the skin was 0.001% 8-MOP. The duration of application leading to the lowest MPD was 30 min. Greatest photosensitization was achieved when UVA irradiation was performed between 0 and 30 min after 8-MOP removal. These findings showed no significant difference between the three vehicles used. CONCLUSIONS: Based on our data we recommend application of 0.001% 8-MOP in a water-in-oil cream for 30 min. Irradiation with UVA should be performed within 30 min after removal of 8-MOP cream, as there is a rapid decrease in photosensitivity thereafter.

Cream psoralen plus ultraviolet A therapy for granuloma annulare.

BACKGROUND: Treatment modalities for granuloma annulare (GA) often remain unsatisfactory or can be accompanied by potentially hazardous side-effects. Psoralen plus ultraviolet (UV) A (PUVA) bath photochemotherapy has been reported to be highly effective in the treatment of GA. Another form of topical PUVA therapy, using 8-methoxypsoralen-containing cream or gel preparations, has been proven to be as effective as bath PUVA therapy in the treatment of palmoplantar dermatoses. OBJECTIVES: To assess the efficacy of cream PUVA photochemotherapy in patients with GA. METHODS: Five patients with GA were treated. The diagnosis was confirmed by pretreatment skin biopsies. Cream PUVA therapy was performed four times a week: the mean number of treatments was 26 (range 17-40) and mean cumulative UVA dose was 55.9 J cm-2 (range 18.2-109.2). RESULTS: Cream PUVA photochemotherapy induced significant clinical improvement (one patient) or clearance (four patients) of GA in all patients. Clearance was documented clinically and histopathologically. CONCLUSIONS: Cream PUVA phototherapy can be highly effective in patients affected by localized forms of GA.

[Treatment of plaque-type psoriasis with cream-PUVA therapy]. / Creme-PUVA-Photochemotherapie bei chronisch stationärer Psoriasis vulgaris.

PUVA-bath therapy has developed into first line topical PUVA therapy in the treatment of psoriasis. Because of logistical and economic problems, bath PUVA may be difficult to administer. Recently, cream-PUVA therapy has been described as an alternative mode of topical therapy. We treated two patients with moderate plaque-type psoriasis with this new topical approach. 0,0006% 8-methoxypsoralen cream was applied for 1 hour, directly followed by increasing doses of UVA. The number of treatments needed for clearance were 34 and 40. The cumulative UVA dosages were 71.6 and 84 J/cm(2) respectively. Our data document that cream-PUVA therapy is an effective and safe variation of topical PUVA therapy, which may develop into first line photochemotherapy for patients with moderate plaque-type psoriasis.

PUVA-cream photochemotherapy for the treatment of localized scleroderma.

BACKGROUND: The efforts to treat localized scleroderma, including therapies with potentially hazardous side effects, are often unsatisfactory. Recently, PUVA-bath photochemotherapy has been proven highly effective in the treatment of localized scleroderma. Another form of topical PUVA therapy, 8-methoxypsoralen (8-MOP) containing cream or gel preparations, has been proven to be as effective as PUVA-bath therapy for palmoplantar dermatoses. OBJECTIVE: We sought to assess the efficacy of PUVA-cream photochemotherapy in patients with localized scleroderma. METHODS: Four patients with localized scleroderma were included in the study. Diagnosis was confirmed by 20 MHz ultrasound assessment as well as pretreatment skin biopsy specimens from lesional skin. PUVA-cream therapy was performed 4 times a week; all patients received 30 treatments. RESULTS: PUVA-cream photochemotherapy induced significant clinical improvement or clearance of localized scleroderma in all patients. Clearance was documented by clinical features as well as by 20 MHz ultrasound and histopathologic analysis. CONCLUSION: PUVA-cream phototherapy can be highly effective in patients with localized scleroderma even if previous therapy was unsuccessful.

[The UV record. Document for quality control, therapy planning and risk assessment in dermatologic photo- and photochemotherapy]. / Der UV-Pass. Instrument der Qualitätskontrolle, Therapieplanung und Risikoabschätzung bei dermatologischer Photo- und Photochemotherapie.

Ultraviolet (UV-) radiation therapy as a mono- or combination therapy (UV-A, UV-A1, UV-B, SUP, UV-B311) or as photochemotherapy with photosensitization (systemic PUVA-, bath PUVA-, topical PUVA-therapy) are successfully used for the treatment of several dermatological disorders. Long-term side effects of natural UV (sun light) include photoaging and induction of skin tumors. At present, the relevance of in-vitro findings of potential tumor induction in animals through therapeutic levels of UV radiation is a matter of debate. To assess these risks, information on treated location, kind of UV radiation and cumulative UV doses are required. Practically this information is barely accessible. This makes decisions on possible therapies difficult. To solve this problem we propose to use an "UV pass". At the end of each UV radiation cycle, the body location, the type of radiation and the cumulative dose are documented and this pass is given to the patient. This will improve the information transfer if the doctor is changed, as well as facilitating decisions about certain therapies and calculation of long-term risks of UV radiation. Finally it will improve the quality of UV photo- and photochemotherapy.

Phototherapy for atopic eczema with narrow-band UVB.

Management of atopic dermatitis has been less than satisfactory. Conventional therapy has not been particularly successful, and prolonged use of topical corticosteroids and systemic immunosuppressant drugs (eg, corticosteroids, cyclosporine, azathioprine) can result in severe cutaneous and systemic effects. We decided to evaluate the effect of UVB at 311 nm to treat 5 patients with moderate to severe atopic dermatitis. In each patient a mean cumulative dose of 9.2 J/cm2 was applied over a mean of 19 irradiations. Narrow-band UVB notably reduced atopic dermatitis after 3 weeks in all patients.

Ozone depletes tocopherols and tocotrienols topically applied to murine skin.

To evaluate ozone damage to hairless mouse skin, two parameters of oxidative damage, vitamin E depletion and malondialdehyde (MDA) production, were measured in vitamin E-enriched and in control skin from mice exposed to ozone (10 ppm). A 5% vitamin E solution (tocotrienol-rich fraction, TRF) in polyethylene glycol (PEG) was applied to 2 sites on the back of hairless mice, PEG to 2 sites. After 2 h, the sites were washed, one of each pair of sites covered and the mice exposed ozone for 2 h. Ozone exposure (compared with covered sites) increased epidermal MDA in PEG-treated sites, while vitamin E was unchanged. In contrast, ozone exposure significantly depleted vitamin E in TRF-treated sites, while significant MDA accumulation was prevented. This is the first demonstration that ozone exposure causes damage to cutaneous lipids, an effect which can be attenuated by vitamin E application.

Ursodeoxycholic acid for liver disease associated with cystic fibrosis: a double-blind multicenter trial. The Italian Group for the Study of Ursodeoxycholic Acid in Cystic Fibrosis.

Liver disease is increasingly recognized as a major cause of morbidity in cystic fibrosis (CF). Preliminary data suggest that ursodeoxycholic acid (UDCA) may be beneficial for treatment of this manifestation. We performed a double-blind, multicenter trial in these patients to establish efficacy and safety of UDCA in terms of the improvement of clinical and nutritional indicators besides standard liver function tests. We also intended to establish whether taurine supplementation has a beneficial effect in patients receiving UDCA. From June to December 1990, we enrolled in 12 centers 55 CF patients with liver disease (39 male subjects; median age, 13.8 years). They were randomly assigned to receive for 1 year one of the following treatments: UDCA (15 mg/kg body weight daily) plus taurine (30 mg/kg body weight daily), UDCA plus placebo, placebo plus taurine, or double placebo. Clinical and laboratory evaluations were performed every 3 months. After 1 year, deterioration of overall clinical conditions, as indicated by the Shwachman-Kulczycki score (SKS), occurred in patients who received placebo but not in those who received UDCA (P = .025). Patients treated with UDCA also showed an improvement in gamma-glutamyl transpeptidase (GGT) (P = .004) and 5'-nucleotidase (P = .006) levels. Treatment with taurine was followed by a significant increase in serum prealbumin levels (P = .053), a trend toward a reduction in fat malabsorption, and no effect on the biochemical profile. No severe side effects occurred with any treatment. Thus, we concluded that UDCA administration improves clinical and biochemical parameters in CF patients with liver disease. Taurine supplementation may be indicated in patients with severe pancreatic insufficiency and poor nutritional status.

Alpha-lipoic acid supplementation prevents symptoms of vitamin E deficiency.

alpha-Lipoic acid, an essential cofactor in mitochondrial dehydrogenases, has recently been shown to be a potent antioxidant in vitro, as well as being capable of regenerating vitamin E in vitro. In this study, using a new animal model for rapid vitamin E deficiency in adult animals and a new technique for tissue extraction of oxidized and reduced alpha-lipoic acid, we examined the antioxidant action of alpha-lipoic acid in vivo. Vitamin E-deficient adult hairless mice displayed obvious symptoms of deficiency within five weeks, but if the diet was supplemented with alpha-lipoic acid the animals were completely protected. At five weeks on a vitamin E-deficient diet animals exhibited similar decreases in tissue vitamin E levels, whether supplemented or unsupplemented with alpha-lipoic acid: vitamin E levels in liver, kidney, heart, and skin decreased 70 to 85%; levels in brain decreased only 25%. These data show that there was no effect of alpha-lipoic acid supplementation on vitamin E tissue concentrations, arguing against a role for alpha-lipoic acid in regenerating vitamin E in vivo.

Parenteral calcitonin for metabolic bone disease associated with primary biliary cirrhosis.

No satisfactory treatment is available for metabolic bone disease associated with primary biliary cirrhosis. On the basis of the similarities to postmenopausal osteoporosis, the rationale exists for calcitonin to be tested in clinical studies in patients with primary biliary cirrhosis-associated osteoporosis. We evaluated the effect of calcitonin on bone metabolism and mineral density in 25 women with primary biliary cirrhosis and severe osteopenia. After 6 mo of observation, patients received a synthetic calcitonin or a control treatment consisting of less than one hundredth of the recommended dose of porcine calcitonin. The two treatments were administered in sequence to each patient for two 6-mo periods, with a 3-mo washout between them, according to a crossover design. After the observation period, oral calcium supplementation was started. Bone mineral density was measured by dual-photon absorptiometry of the lumbar spine at study entry and at the beginning and the end of each treatment period. During the observation period bone mineral density fell by 3.5% whereas during the following 6 mo it increased in both the patients who received calcitonin (4.3%) and those who received the control treatment (4.9%). Conversely, after the crossover, bone mineral density decreased during both calcitonin (-2.7%) and control treatment (-2.9%). A significant difference was observed between the two periods but not between the two treatments or between the two sequences of treatment administration. In conclusion, our findings indicate that parenterally administered calcitonin for 6 mo is ineffective in halting bone loss in patients with primary biliary cirrhosis-associated metabolic bone disease, whereas calcium supplementation may have a transient beneficial effect.

Effects of ursodeoxycholic acid therapy for liver disease associated with cystic fibrosis.

The hydrophilic bile acid ursodeoxycholic acid (UDCA) has recently been shown to improve indexes of liver function in adult patients with various liver diseases. The clinical and biochemical responses to UDCA administration (10 to 15 mg/kg body weight per day) were therefore investigated in nine patients with cystic fibrosis and evidence of liver disease. All patients were receiving pancreatic enzymes and taurine supplementation. Liver function tests were done and serum bile acid concentrations and biliary bile acid composition were determined before and during UDCA therapy; fat balance studies and fecal bile acid excretion were carried out before and 6 months after UDCA treatment. After 2 months of bile acid therapy, biliary bile acid composition was enriched in UDCA from approximately 5% before treatment to 25%, at the expense of cholic and chenodeoxycholic acids, thus making the pool more hydrophilic. This enrichment is lower than that reported for adults with chronic liver diseases. Serum concentrations of UDCA increased significantly but variably. UDCA became the predominant fecal bile acid excreted (12% to 67%), indicating a variable absorption of the administered bile acid. Liver function improved in all patients after 2 to 6 months of therapy, although the degree of improvement (aspartate aminotransferase, -34%; alanine aminotransferase, -41%; gamma-glutamyltranspeptidase, -41% alkaline phosphatase, -19%) was lower than that observed in adults with chronic liver diseases. Mean coefficient of fat absorption and growth rate were, on average, unaffected by UDCA therapy, although an improvement was noted for three patients with greater severity of steatorrhea. The study indicates that UDCA can be used safely in this patient population but that higher doses of UDCA may be of greater benefit in the treatment of the liver disease associated with cystic fibrosis.

Efficacy and safety of a combination of chenodeoxycholic acid and ursodeoxycholic acid for gallstone dissolution: a comparison with ursodeoxycholic acid alone.

Chenodeoxycholic acid (CDC) and ursodeoxycholic acid (UDC) have distinct physicochemical and metabolic properties which, being complementary, should favor more rapid removal of cholesterol from gallstones when both bile acids are administered together. To see if the combination is more effective and well tolerated, we have compared 5 mg/kg of CDC plus 5 mg/kg of UDC with a 10-mg/kg dose of UDC alone in 120 patients with radiolucent, sonographically confirmed gallstones and characteristics favoring complete dissolution. Ursodeoxycholic acid was chosen as the reference because it dissolves stones faster and is better tolerated than CDC. To minimize the influence of stone size, the major determinant of dissolution, patients were divided, on admission, into two groups according to the maximum stone diameter: 50 had stones less than or equal to 5 mm, 70 had stones greater than 5 mm but less than 15 mm. The effects of treatment on stone dissolution evaluated by cholecystography and ultrasonography at 6, 12, and 24 mo, were analyzed by the actuarial life-table method. In the group with smaller stones, significantly more patients had obtained complete dissolution after treatment with the combination (52%) than after treatment with UDC alone (24%) at 6 mo. After longer periods, results were still better with the combination, although the differences from UDC alone became smaller. In the patients with larger stones, rates of complete and partial dissolutions were higher after treatment with the combination (51% vs. 24% with UDC) at 6 mo and again the differences had become smaller after longer treatment. Although not statistically significant, stone calcification occurred more often with UDC (7 cases) than with the combination (1 case). We conclude that CDC plus UDC is preferable to UDC alone because it dissolves stones more quickly, with a lower incidence of stone calcification, and may result in reduced cost of treatment.

Effects of a preparation containing a standardized ginseng extract combined with trace elements and multivitamins against hepatotoxin-induced chronic liver disease in the elderly.

A preparation containing a standardized ginseng extract which has been shown to exert anti-hepatotoxic activity in vitro, combined with trace elements and multi-vitamins was compared to placebo in 24 elderly out-patients with toxin-induced (alcohol and drugs) chronic liver disease in order to evaluate its effect on liver function. Each patient was blindly treated either with the preparation containing ginseng extract or placebo for 12 weeks. The preparation containing ginseng extract significantly modified bromsulphthalein retention and blood zinc levels when compared to pre-treatment levels and to placebo. Serum bile acids, and gamma-glutamyl transpeptidase before and after a fatty meal were significantly reduced after treatment with the test preparation and not with placebo. When the two treatment groups were compared, however, no significant difference in these parameters was observed. These results suggest that treatment with the preparation containing ginseng extract could improve the detoxifying activity of the liver in elderly patients with toxin-induced chronic liver disease.