Percutaneous progesterone delivery via cream or gel application in postmenopausal women: a randomized cross-over study of progesterone levels in serum, whole blood, saliva, and capillary blood.

OBJECTIVE: This study aims to investigate the distribution of progesterone in venous whole blood, venous serum, fingertip capillary blood, and saliva after its topical application in both cream and gel formulations. METHODS: Ten postmenopausal women were randomized to receive 80 mg of progesterone cream or gel applied daily for 14 days, crossing over after a 14-day washout. On the last day of each treatment period, venous blood, fingertip capillary blood, and saliva were sampled frequently for 24 hours after the final application. RESULTS: After progesterone cream or gel application, serum progesterone levels rose gradually, reaching a peak at 9 and 8 hours, respectively; AUC(0-24) h was significantly higher with cream (12.39 vs 8.32 ng h mL(-1), P = 0.0391). Whole venous blood levels followed a pattern similar to that of serum but were considerably lower. Saliva progesterone showed a peak at 1 and 6 hours after cream and gel application, respectively, and C(max) was comparable with cream and gel. Saliva AUC(0-24) h was substantially higher than the corresponding area under the curve for serum or whole blood but did not differ significantly by delivery method (39.02 and 58.37 ng h mL(-1), P = 0.69). In capillary blood, C(max) was reached at the same time (8 h) and was similar with both formulations; AUC(0-24) h was also similar with both formulations (1,056 ng h mL(-1) for cream and 999 ng h mL(-1) for gel) but was dramatically higher than the corresponding areas under the curve for venous serum and whole blood. CONCLUSIONS: After application of topical progesterone, saliva and capillary blood levels are approximately 10-fold and 100-fold greater, respectively, than those seen in serum or whole blood. High capillary blood and saliva levels indicate high absorption and transport of progesterone to tissues. Reliance on serum levels of progesterone for monitoring topical dose could lead to underestimation of tissue levels and consequent overdose.

Effect of subcutaneous depot-medroxyprogesterone acetate (DMPA-SC) on serum androgen markers in normal-weight, obese, and extremely obese women.

BACKGROUND: The effects of subcutaneous depo-medroxyprogesterone acetate (DMPA-SC) injection on androgenic markers in obese women have not previously been studied. STUDY DESIGN: Five normal-weight [body mass index (BMI)=18.5-24.9 kg/m²], five obese (BMI=30-39.9 kg/m²) and five extremely obese (BMI≥40 kg/m²) women were recruited for this prospective experimental study in which 104 mg DMPA-SC was administered at baseline and 12 weeks later. Serum levels of total testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), 3α-androstanediol glucuronide and sex hormone-binding globulin (SHBG) were quantified by immunoassay methods at baseline and at 13 and 26 weeks following the first injection; free T was calculated. RESULTS: At baseline, obese women had lower levels of A and SHBG and higher total and free T levels than normal-weight women. There were a statistically significant decrease in the levels from baseline to week 26 among all three BMI classes for A, total T and SHBG (p≤.03) and an increase from baseline to week 26 in weight (p=.02). In addition, there was a statistically significant decrease in DHEAS from baseline to week 13 among all three BMI classes (p=.01), which was not sustained at week 26 (p>.1). Overall, the three groups responded similarly to all changes at week 13, and there were no statistically significant differences between groups at any time point (p≥.06). CONCLUSION: DMPA-SC use in normal-weight, obese and extremely obese women can decrease serum androgen markers.

Shear bond strengths of molar tubes bonded with different adhesives.

AIMS: This study determined which molar base retentive designs produced the greatest shear bond strength (SBS) to human molars when using different adhesives. METHODS: One hundred and fifty extracted human molars were divided into 15 groups of 10. The tested molar tube bases included two stainless steel experimental base designs, a titanium single mesh 80 gauge base, a stainless steel double mesh 150 gauge under 80 gauge base and a stainless steel single mesh 80 gauge base. Each base was bonded with Transbond XT, Pad Lock and Light Bond. One primer, Assure, was used for all specimens. Bonded specimens were stored in water for 7 days and SBS was measured on an Instron testing machine with a crosshead speed of 1 mm/minute. Two-way ANOVA were performed with post-hoc comparisons of the means to determine any statistical differences in SBS. The significance level was set at 5 per cent. RESULTS: The brackets, adhesives and combinations of brackets and adhesives used had a significant effect on SBS (Bracket: p < 0.001; Adhesive: p = 0.020; Interaction: p = 0.005). Mean SBS differed significantly for the adhesives: Light Bond, Pad Lock and Transbond (p < 0.001, p = 0.001 and p < 0.001, respectively). In general, the stainless steel single mesh 80 gauge base and Light Bond adhesive produced the greatest SBS. CONCLUSION: The clinician's choice of bracket and adhesive affect the SBS of bonded molar attachments.

13C-urea breath test for Helicobacter pylori in young children: cut-off point determination by finite mixture model.

The 13C-urea breath test (UBT) is currently regarded as one of the most important noninvasive diagnostic methods for detecting Helicobacter pylori (H. pylori) infection in adults and children. However, for infants and young children, the standard for UBT interpretation has not been validated, and its reliability has not been established for diagnosing H. pylori infection in this group. The primary outcome data from UBT consist of mixture data, which come from subjects whose H. pylori infection classifications are unconfirmed. In this paper, we propose the finite mixture distribution method to identify a reliable UBT cut-off value in a large baseline sample in which gastric biopsy is not available to confirm the H. pylori infection in younger children. Maximum likelihood estimators of the parameters in the mixture model were obtained using an expectation maximization (EM) algorithm. The standard deviation of the cut-off point was estimated by bootstrap methods. We applied the same analytical methods to the UBT results yielded from the follow up, as well as the overall UBT results in the longitudinal cohort data. The cut-off points from those UBT data sets are similar. The advantage of the finite mixture model is that it may be used to calculate sensitivity and specificity in the absence of other diagnostic tests.

Phenotypic differences between esophageal and gastric intestinal metaplasia.

Intestinal metaplasia is a cancer precursor in the esophagus and the stomach. Marked differences exist between the carcinogenic processes in the two locations in terms of natural history and clinical significance. We investigated biopsies from 52 patients with Barrett's esophagus and from 50 patients with gastric intestinal metaplasia in an attempt to throw light on their pathogenic processes. Morphologic characteristics, presence of Helicobacter pylori (H. pylori), and markers of differentiation, inflammation, and proliferation were evaluated by histochemical and immunohistochemical techniques. The area covered by incomplete type of intestinal metaplasia and the proportion of sulfomucins were significantly higher in the esophagus than in the stomach. Immunoreactivity with MUC1, MUC2, MUC5AC, Das-1, cytokeratins 7 and 20, inducible nitric oxide synthase and cyclooxygenase-2 antibodies was also significantly greater in Barrett's esophagus than in gastric intestinal metaplasia. In gastric intestinal metaplasia, the presence of MUC1, MUC5AC, Das-1 and cytokeratin 7 was restricted to areas with the incomplete type of metaplasia. Cell proliferation (Ki-67) was significantly higher in Barrett's esophagus than in gastric intestinal metaplasia. H. pylori was absent in all of the patients with Barrett's esophagus, while it was present in 70% of the patients with gastric intestinal metaplasia. Our observations made clear that Barrett's esophagus shares some phenotypic characteristics with gastric intestinal metaplasia, leading us to suggest that both could arise in response to injuries with eventual carcinogenic potential. However, the progression to more advanced lesions could be modulated by the nature of the carcinogenic insult.

Histopathology of gastritis in Helicobacter pylori-infected children from populations at high and low gastric cancer risk.

Infection with Helicobacter pylori has been recognized as a cause of gastric carcinoma. Although the neoplasia is always detected in adults, the infection starts in childhood. It has been reported that early age at first infection is a determinant of gastric cancer risk. In this study, we examined the histopathology of the gastric mucosa in infected children from a population at high risk for gastric cancer (Pasto, Colombia) and compared it with that of a lower-risk population (New Orleans, LA). Gastric biopsies obtained from antrum and corpus were stained with hematoxylin and eosin and Steiner's silver method. Immunohistochemical stains were used to identify B lymphocytes (CD20), T lymphocytes (CD3 and CD8), macrophages (CD68), and polymorphonuclear neutrophil myeloperoxidase. Morphometric techniques were used to evaluate the immunohistochemical stains. In both populations, the inflammatory lesions were seen predominantly in the antrum. Compared with children from the lower-risk populations, children from the higher-risk population exhibited more severe polymorphonuclear neutrophil infiltration, stromal and intraepithelial lymphocyte infiltration, mucus depletion, and H. pylori colonization density. Regenerative activity was significantly more marked in the lower-risk population. Morphometric analysis of immunohistochemical stains showed increased representation of T lymphocytes and macrophages in the higher-risk population. Most T lymphocytes stained positive for CD8, a marker of suppressor/cytotoxic cells. B lymphocytes were relatively more abundant in the lower-risk population. The possibility that the aforementioned characteristics of H. pylori infection in children are related to cancer risk in adults is discussed.