Adult height in patients with childhood onset atopic dermatitis

Cross sectional studies have reported impaired growth in children with atopic dermatitis. If this growth impairment is irreversible, it would be expected to adversely influence final height attainment. The standing heights and other anthropometric parameters were assessed in 35 adults with onset of atopic dermatitis before 5 years of age and a control group of 35 adults with adult onset contact dermatitis or psoriasis. There was no significant difference in the standing height SD score, mid-parental height SD score, sitting height SD score, subischial leg length SD score, nor body mass index between the atopic dermatitis and control groups. The standing height SD score was not significantly different among: (a) patients with atopic dermatitis affecting less than 50% of their body surface area and those with greater than 50% affected; (b) patients using the four different potency topical corticosteroids; and (c) patients with atopic dermatitis without asthma and those with coexisting asthma. It is concluded that short stature is not a feature of our group of adult patients with onset of atopic dermatitis before 5 years of age, continuing into adulthood, and severe enough to require specialist care. This suggests that if growth impairment occurs in childhood, it is likely to be temporary and reversible.     

Effect of peritoneal fluid from patients with mild and severe endometriosis on endometrial stromal cell proliferation

The aim of this study was to evaluate and compare the mitogenic effect of peritoneal fluid (PF) from women with mild and severe endometriosis on the endometrial stromal cell proliferation. Increasing concentrations of PF from women with and without mild or severe endometriosis were added to primary endometrial stromal cell cultures and³H-thymidine incorporation was used to assess DNA synthesis in these cultures. PF from women with mild endometriosis induced a statistically significant dose-dependent increase in stromal cell thymidine uptake ranged from 5.8 to 14.5 fold, whereas PF from women with severe endometriosis produced an average 51% inhibition of stromal cell proliferation of compared with cells exposed to non-endometriosis PF or exposed to nutrient medium supplemented with 2.5% calf serum alone. PF samples from patients with stage I endometriosis induced a statistically dose-dependent increase in stromal cell proliferation, whereas PF from patients with stage IV endometriosis caused a significant inhibition.     

Hydrogen peroxide inhibits gap junctional intercellular communication in glutathione sufficient but not glutathione deficient cells

Cell to cell communication via gap junctions is essential in the maintenance of the homeostatic balance of multicellular organisms. Aberrant intercellular gap junctional communication (GJIC) has been implicated in tumor promotion, neuropathy and teratogenesis. Oxidative stress has also been implicated in similar pathologies such as cancer. We report a potential link between oxidative stress and GJIC. Hydrogen peroxide, a known tumor promoter, inhibited GJIC in WB-F344 rat liver epithelial cells with an I50 value of 200 microM. Inhibition of GJIC by H2O2 was reversible as indicated by the complete recovery of GJIC with the removal of H2O2 via a change of fresh media. Free radical scavengers, such as t-butyl alcohol, propylgallate, and Trolox, did not prevent the inhibition of GJIC by H2O2, which indicated that the effects of H2O2 on GJIC was probably not a consequence of aqueous free radical damage. The depletion of intracellular GSH reversed the inhibitory effect of H2O2 on GJIC. The treatment of glutathione- sufficient cells with H2O2 resulted in the hyperphosphorylation of connexin43, which is the basic subunit of the hexameric gap junction protein, as determined by Western blot analysis. TPA, a well-known tumor promoter, also inhibits GJIC via hyperphosphorylation of GJIC, which is a result of protein kinase-C activation. However, H2O2 also induced hyperphosphorylation in GSH-deficient cells that had normal rates of GJIC. Therefore, the mechanism of GJIC inhibition must be different from the TPA-pathway and involves GSH.      

Dietary polyamines promote the growth of azoxymethane-induced aberrant crypt foci in rat colon

We have examined whether dietary polyamines influence the formation and initial growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rat colon. Effects of a combination of dietary polyamines at three dose levels (putrescine: 50, 280, 740 nmol/g; spermidine: 10, 261, 763 nmol/g; spermine: 1, 31, 91 nmol/g) in the polyamine-poor AIN-76A diet were studied in animals in two different experimental situations: animals treated with AOM alone and animals treated with AOM + difluoromethylornithine (DFMO), a specific inhibitor of endogenous polyamine synthesis. In both experimental situations, dietary polyamines enhanced the growth of ACF, expressed as the number of large ACF (foci with three or more aberrant crypts, ACF > or = 3), whereas the formation of ACF, expressed as the number of ACF, was apparently not altered. In animals treated with AOM alone, maximal growth enhancing effect on ACF was nearly obtained with the median level of dietary polyamine. In rats fed a low polyamine diet, basic AIN-76A, DFMO reduced the growth of AOM-induced ACF by 83%. This inhibitory effect of DFMO was counteracted by dietary polyamines in a dose- dependent manner, and it was abolished at the highest level of polyamines. In conclusion, it was demonstrated that dietary polyamines are able to enhance the growth of AOM-induced ACF. Further, dietary polyamines reversed the DFMO-caused inhibition of ACF growth, probably by compensating for the DFMO-reduced endogenous polyamine synthesis.      

Effect of the viable-yellow (A(vy)) agouti allele on skin tumorigenesis and humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice

We previously reported that papillomas can arise from the follicular epithelium of v-Ha-ras transgenic TGxAC mice. Since the viable-yellow mutation (A(vy)) of the mouse agouti gene which regulates coat color pigmentation by acting within the micro-environment of the hair follicle has been shown to function as a tumor promoter in the liver, we hypothesized that it may also play a role in TGxAC skin tumorigenesis. Endogenous agouti protein product was detected in the outer root sheath of anagen hair follicles following plucking of the hair shaft, but not in the interfollicular epithelium, in TGxAC mice on an FVB/N genetic background. It was also detected in papillomas from these mice produced by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment or plucking. Expression of the A(vy) allele in the v-Ha-ras transgenic TGxAC mouse line results in an approximately 2-fold increase in papilloma development compared with controls which did not carry the A(vy) allele following twice-weekly treatment with 1.25, 2.5 or 5.0 microg TPA. In addition, TPA-treated, papilloma-bearing F1 mice which carried the A(vy) allele, but not F1 mice which did not carry the A(vy) allele, exhibited a syndrome of humoral hypercalcemia mediated by parathyroid hormone-related protein (PTHrP) that led to weight loss, hypercalcemia and hypophosphatemia. Thus, we conclude that the A(vy) allele can influence the development of skin tumors and PTHrP-mediated humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice.      

Estimation of the dietary intake of cadmium, lead, mercury, and arsenic by the population of Santiago (Chile) using a Total Diet Study.

Dietary intake of arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) by the population of Santiago (Chile) was determined using a Total Diet Study in the market basket modality. After conducting a survey of the foods consumed in the last 24 h, the most consumed food products were included in the basket. Subsequently, they were cooked or prepared according to typical Chilean procedures and grouped into 17 food categories according to their chemical characteristics. The fish and shellfish group had the highest contents of As (1351 ng/g wet weight, ww), Cd (277 ng/g ww), and Hg (48 ng/g ww), while the sugar group had the highest content of Pb (251 ng/g ww). For a person with a body weight of 68 kg, the dietary intakes of As (77 microg/day), Cd (20 microg/day), Hg (5 microg/day), and Pb (206 microg/day) are lower than the provisional tolerable weekly intake values established by the FAO/WHO. Consequently, the total intakes of As, Cd, Hg, and Pb in Santiago (Chile) are within the limits estimated as safe.     

The polysaccharide antibody response after Streptococcus pneumoniae vaccination is differentially enhanced or suppressed by 3,4-dichloropropionanilide and 2,4-dichlorophenoxyacetic acid.

Propanil (3,4-dichloropropionanilide) and 2,4-D (2,4-dichlorophenoxyacetic acid) are commonly used herbicides that have toxic effects on the immune system. The present study determined the effect of exposure to these chemicals on the immune response to a bacterial vaccine. The antibody responses to the T-independent type 2 antigen, phosphorylcholine (PC) and the T-dependent antigen, pneumococcal surface protein A (PspA) were characterized in C57BL/6 mice after heat-killed Streptococcus pneumoniae (HKSP) immunization and single or mixture herbicide exposure. Propanil exposure significantly increased the number of PC-specific IgM, IgG2b, and IgG3 antibody-secreting B cells (ASC) in the spleen 4-6-fold over control animals in a dose-dependent manner. However, the number of ASC in the bone marrow and serum titers were comparable in control and propanil-treated mice. In contrast, 2,4-D exposure decreased the number of PC-specific IgM and IgG bone marrow ASC 2-3-fold from control animals. The decrease in bone marrow ASC in 2,4-D-treated mice corresponded to a 3-4-fold decrease in PC-specific IgM, IgG2b, and IgG3 serum titers compared to control mice. The number of ASC in the spleens of 2,4-D-treated mice was, however, comparable to control mice. The antibody response to PspA was not affected by any of the treatments. There were no mixture interactions between the two herbicides in any of the responses measured. These results characterize the primary PC-specific antibody response in the bone marrow, spleen, and serum after HKSP vaccination and herbicide exposure. The differential effects of propanil and 2,4-D on the antibody response to a bacterial vaccine demonstrate the potential of chemical exposure to augment or suppress immune responses to vaccines and infectious diseases.     

Clinical improvement in patients with orthostatic intolerance after treatment with bisoprolol and fludrocortisone

Orthostatic intolerance is the development of disabling symptoms upon assuming an upright posture that are relieved partially by resuming the supine position. Postural tachycardia syndrome (POTS) is an orthostatic intolerance syndrome characterized by palpitations because of excessive orthostatic sinus tachycardia, lightheadedness, tremor, and near-syncope. Patients usually undergo extensive medical, cardiac, endocrine, neurologic, and psychiatric evaluation, which usually fails to identify a specific abnormality. The authors investigated the autonomic and hemodynamic profile of patients with POTS and the effectiveness of bisoprolol and fludrocortisone. The authors evaluated 11 female patients with POTS before and after medical treatment with a cardioselective bisoprolol -blocker or fludrocortisone, or both, and 11 age-matched control patients. Variability of heart rate and systolic blood pressure was assessed by fast Fourier transform, and spontaneous baroreceptor gain was assessed by use of the temporal sequences slope and index. Modelflow was used to quantify hemodynamics. Symptoms in all patients improved greatly after medication. The autonomic and hemodynamic impairment observed in patients with POTS, particularly after orthostatic stress, is treated effectively with bisoprolol or fludrocortisone or both. These results need further confirmation in a controlled double-blind study. Proper medical treatment improves dramatically the clinical and autonomic-hemodynamic disturbances observed in patients with POTS. The data support the hypothesis that POTS is the result of a hyperadrenergic activation or hypovolemia during orthostasis.     

Role of the CDKN2A locus in patients with multiple primary melanomas.

PURPOSE: We have studied a consecutive case series of patients with multiple primary melanoma (MPM) for the involvement of the melanoma susceptibility loci CDKN2A and CDK4. PATIENTS AND METHODS: One hundred four MPM patients (81 patients with two primary melanomas, 14 with three, five with four, one with five, two with six, and one with seven) were included. RESULTS: Seven different CDKN2A germline mutations were identified in 17 patients (16.3%). In total, we identified 15 CDKN2A exon 2, one exon 1alpha missense mutation, and one exon 1beta frameshift mutation. The age of onset was significantly lower and the number of primary melanomas higher in patients with mutations. CDKN2A mutations were more frequent in patients with familial history of melanoma (35.5%) compared with patients without (8.2%), with a relative risk (RR) of 4.32 (95% CI, 1.76 to 10.64; P = .001), and in patients with more than two melanomas (39.1%) compared with patients with only two melanomas (10%) with an RR of 3.29 (95% CI, 1.7 to 6.3; P = .002). The A148T polymorphism was more frequent in patients with MPMs than in the control population (P = .05). A variant of uncertain significance, A127S, was also detected in one patient. No CDK4 mutations were identified, suggesting that it has a low impact in susceptibility to MPM. CONCLUSION: MPM patients are good candidates for CDKN2A mutational screening. These patients and some of their siblings should be included in a program of specific follow-up with total body photography and digital dermoscopy, which will result in the early detection of melanoma in this subset of high-risk patients and improve phenotypic characterization.