Bioavailability of estradiol as a marker for breast cancer risk assessment.

The search for a hormonal marker in breast cancer has centered on estrogens and their metabolites. However, direct measurements of total amounts of these steroids have shown no convincing or consistent differences between normal women and women with breast cancer. The purpose of this study was to measure the percentages of non-protein-bound estradiol (%NPBE) and of estradiol bound to albumin (%ABE) and the levels of sex hormone-binding globulin (SHBG) both in women with breast cancer and in those free of disease. Serum was collected and analyzed within 2 weeks, using an isodialysis method. The mean %NPBE and %ABE were significantly higher in 32 women with breast cancer (1.73 and 64.0%, respectively) than in 32 matched disease-free women (1.43 and 48.6%, respectively) (P less than 0.001). No significant difference was observed in the levels of plasma albumin when the above matched groups were compared. However, plasma levels of SHBG were significantly lower in the women with breast cancer than in either the control population or matched controls. In this finding we differ from previous studies which reported no significant differences in the mean plasma levels of SHBG. In our study, the increased %NPBE and %ABE in some patients with breast cancer may be related to a lower level of plasma SHBG; other factors, too, may affect the distribution of estradiol. Our results support the hypothesis than an increase in %NPBE and %ABE or both may indicate an increased risk of breast cancer.

Evacuation proctography in normal volunteers.

Constipated patients evaluated by evacuation proctography may be subjected to vigorous medical therapy or surgery, even colectomy, based on radiographic findings that have been called "abnormal" in the literature. Criteria for normal defecography are not uniformly established, nor has correlation of structural or functional findings with symptoms been clearly documented. We prospectively studied 21 asymptomatic volunteers to assess the frequency of findings in a control population, and to establish a quantitative measure of normal rectal emptying. Standard defecography technique demonstrated rectocele, intussusception, pelvic descent, or puborectalis spasm in 14/21 volunteers (67%). The range of rectal emptying was 12.5% to 100%, with four subjects (19%) evacuating less than or equal to 40% of the barium paste. There was no correlation between severity of radiographic findings and degree of evacuation. Defecography results in patients being considered for symptomatic intervention should be interpreted cautiously, given the wide range of normal variation in a control population.

Effects of thyroid status and choice of USP preparation on the pharmacokinetics of propylthiouracil in the beagle dog.

In vitro dissolution profile testing of 12 generic 6-propyl-2-thiouracil (PTU) formulations indicated significant differences in their solubilities in water and in 0.1N hydrochloric acid. Two products, representing the extremes of solubility, were subsequently tested for bioavailability. Bioavailability data from euthyroid, hyperthyroid, and hypothyroid beagle dogs indicated that the rate of PTU absorption varied appreciably between the two generic products studied. These results were consistent with the in vitro dissolution data. Comparisons of the pharmacokinetic parameters obtained for the euthyroid beagle dog to those reported for euthyroid man12 indicated that the beagle dog is an adequate model for PTU disposition in man. These combined results suggest that all generic formulations of PTU are not the same and that the most soluble product may be desirable in situations where rapid absorption is important, such as thyroid storm.

A comparison of body and organ weights, physiologic parameters, and pathologic changes in target organs of rats given combinations of exercise, anabolic hormone, and protein supplementation.

This study was engineered to closely mimic the training protocol of a competitive athlete using repetitive exercise sessions, dietary protein supplementation, and anabolic steroids. The length of the study was 37 days. Thirty-four Sprague Dawley male rats Crl:CD(SD)BR in the weight range of 150 to 175 grams were used. These were randomly divided into four exercise groups, varying protein consumption and anabolic hormone administration. Eight nonexercised control rats were kept separate from the study to act as a comparison for organ weight, hematology, and serology. Exercise consisted of a 30 minute swim three times a week. Parameters recorded were total body weight and percent gain, wet and dry muscle weight of the isolated anterior tibialis, weights of designated organs, hematologic profiles, and serum chemistries including triglycerides, high density and low density lipids. Histopathology of known "target organs" was performed and bone marrow aspirates were taken. Body weights of rats given anabolic steroid, protein supplement, and exercise were the lowest of all groups. Testicular weight was significantly decreased in the anabolic groups. Anabolic groups had the lowest hematocrits of the exercised groups. All serology values were within normal ranges and no pathologic changes were seen in any of the tissues taken from specific "target organs."

Quality assurance for the radiology-emergency interface.

Quality assurance does not have to be a dirty word. Developing indicators, identifying trends, taking action, and reassessing the results can significantly benefit the technical and nursing staff, emergency physicians, radiologists, and, especially, the patients.

Pharmacokinetics and bioavailability of papaverine HCl after intravenous, intracorporeal and penis topical administration in beagle dogs.

Bioavailability and pharmacokinetics of papaverine HCl was studied in beagle dogs following intravenous injection, intracorporeal injection and topically applied gel on the penis. Also the effect of the sorption promoter Labrafil M-1944 CS on the permeation of papaverine from two gel formulations (PT and PTL) containing the co-solvent Transcutol was evaluated. Blood samples were analyzed by high performance liquid chromatography (HPLC). The pharmacokinetic parameters were determined using either curve-fitting (RE-SID) or compartment model independent method (AUC-RPP). The plasma concentration-time profiles show that papaverine HCl pharmacokinetics is best described by an open two-compartment model. The absolute bioavailability of papaverine HCl was determined to be 102.4%, 9.1%, and 12.4%, respectively, following intracorporeal injection, gel PT and gel PTL administration.

Contributions of evacuation proctography and anorectal manometry to evaluation of adults with constipation and defecatory difficulty.

We prospectively evaluated 36 patients who complained of chronic constipation and/or defecatory difficulties to determine the role of anorectal manometry and evacuation proctography in delineating the pathogenesis of these complaints. Twenty patients with constipation also underwent a colonic transit study with radioopaque markers, which identified one group with normal transit (N = 10) and another with slow transit (N = 10). Nine of 36 patients (25%) had inappropriate puborectalis muscle contraction or exhibited weak expulsion efforts during evacuation proctography, and these correlated highly with poor rectal emptying of barium paste (20 +/- 6% vs 61 +/- 5% in patients with normal relaxation; P less than 0.01). However, poor rectal emptying did not correlate with the presence of high-grade intussusceptions, large rectoceles, anorectal angles at rest or with straining, rectal diameter, clinical features, or colonic transit. Moreover, abnormal expulsion patterns as seen with anorectal manometry correlated poorly with the presence of inappropriate puborectalis contraction and decreased rectal emptying by proctography. Although anatomic abnormalities occurred frequently in patients with constipation and/or defecatory difficulties, they were also prevalent in asymptomatic controls. In view of these findings, surgical intervention to correct anatomic abnormalities in patients with constipation and/or defecatory difficulties should be considered only with great caution.

Computerized tomography and adenocarcinoma of the esophagus.

A case of adenocarcinoma of the stomach spreading to the esophagus is described. It was well seen on computerized tomography and appeared more ominous than the esophagram. The latter illustrated an appearance simulating narrowing secondary to peptic esophagitis; the former demonstrated a relatively large encompassing mass. The definitive diagnosis was made during endoscopy and confirmed by biopsy. Although computerized tomography is not considered the method of choice for establishing an abnormality in this organ, it can occasionally help. It can usually show the total extent of the tumor better. Additional cases are presented.

Systemic joint laxity (the hypermobile joint syndrome) is associated with temporomandibular joint dysfunction.

A consecutive series of 37 individuals admitted to the hospital for elective temporomandibular joint (TMJ) reconstructive surgery and 3 seen as outpatients with TMJ disease were evaluated for rheumatic disease or for another etiologic factor that might account for this problem. These 40 patients were screened by history, physical examination, and laboratory study. We soon noticed that many patients had generalized joint laxity. Eighteen of the first 40 individuals satisfied established criteria for the hypermobile joint syndrome. An additional 3 were found to have Ehlers-Danlos syndrome or a forme fruste of this disorder. Many were markedly hypermobile and could perform a number of flexible maneuvers. Although excessive joint laxity is known to be associated with a variety of rheumatic conditions, TMJ disease has not been recognized as one of them. No patient in this series had a systemic inflammatory disorder or any other apparent etiologic factor for TMJ disease. We suggest that there is a cause-and-effect relationship between generalized joint laxity and TMJ disease.