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Biomedical subjects

D L Stahl

Publications and source records attributed to D L Stahl.

8 recordsLinked to original sources

The effect of estrogen usage on the subsequent hormone receptor status of primary breast cancer.

In order to determine if prior use of exogenous estrogens was related to the estrogen receptor (ER) content of primary breast cancers, a retrospective analysis was performed from 536 patients with invasive breast cancer. The patient's age, menopausal status, oral contraceptive or estrogen replacement therapy usage, and the ER and progesterone receptor (PR) content of the breast cancer were recorded for all patients. Hormone usage in premenopausal and postmenopausal patients was compared to ER and PR levels in primary breast cancers using non-parametric testing. Complete information was available from 508 (193 premenopausal and 315 postmenopausal) patients. Breast cancers were ER positive in 72% of postmenopausal patients and 57% of premenopausal patients. The majority of patients received 'Some' form of hormone therapy (111 of 193 premenopausal patients and 233 of 315 postmenopausal patients). Significantly more estrogen receptors were detected in tumors from patients receiving 'some' estrogen therapy compared to 'never' users. Postmenopausal patients 'never receiving estrogen therapy had a lower rate of ER positive tumors (62%) compared to 'some' users (75%, chi2 = 4.99, p < 0.05). The same relationship was seen for PR ('never' users 44% positive, 'some' users 58% positive, chi2 = 5.19, p < 0.05). We conclude that postmenopausal patients who received 'some' estrogen therapy are more likely to have breast cancers that are estrogen receptor and progesterone receptor positive.

Adult↗

Meniscal fixation with an absorbable staple. An experimental study in dogs.

An absorbable staple for meniscal fixation was developed and evaluated in an in vivo canine study. The staple consisted of two rigid barbed legs, made of a copolymer of polyglycolic acid and polylactic acid, connected by a flexible suture made of the same absorbable material. The staple was developed for arthroscopic use, eliminating the risk of nerve or vascular injuries associated with suture fixation. Eighty-two mongrel dogs underwent meniscal repair in this study, which was performed in two sequential parts. An incision was made in the medial meniscus at the peripheral third and was fixed with either the staple or with a single 3-0 PDS suture. The animals from the first part of the study, in which the biocompatibility of a prototype staple design, was evaluated were sacrificed at 3 days, 2 weeks, 6 weeks, 3 months, and 9 months. Those from the second part of the study, in which an improved staple design of the same material, was evaluated were sacrificed at 6 weeks, 4 months, and 1 year. The operated menisci were either examined histologically or were mechanically tested for tensile strength. Absorption of the staple began by 3 months and was almost complete by 1 year. Mechanically, the staple provided greater tensile strength augmentation of the meniscus than suture fixation for up to 4 months. In the long term, there was no difference between the staple and suture in enhancement of healing.

Analysis of Variance↗

The effects of diquat and ciprofibrate on mRNA expression and catalytic activities of hepatic xenobiotic metabolizing and antioxidant enzymes in rat liver.

Although the mechanisms responsible for chemically induced oxidative stress are under intense investigation, little is known about the effects of prooxidant chemicals on the expression of drug-metabolizing enzymes. We examined the effects of diquat (0.1 mmol/kg, ip) and ciprofibrate (0.025% w/w, diet), chemicals which induce oxidative stress via different biochemical mechanisms, on the steady-state messenger RNA (mRNA) levels of six cytochrome P450 enzymes, seven glutathione S-transferase (GST) isoenzymes, UDP-glucuronosyl transferase 1-06 (UGT1*06), gamma-glutamylcysteine synthetase (gamma GCS), NADP(H):quinone oxidoreductase (quinone reductase), Cu/Zn superoxide dismutase (SOD), catalase, and 18S ribosomal RNA in the livers of male Sprague-Dawley rats. Effects of chemical treatments on mRNA levels were compared to changes in catalytic activities for selected enzymes. Ciprofibrate treatment selectively decreased CYP1A2 mRNA expression, whereas both chemicals suppressed CYP3A2 mRNA expression. CYP4A1 mRNA expression and lauric acid hydroxylase activities were induced by ciprofibrate treatment, whereas diquat treatment moderately increased CYP4A1 mRNA levels without affecting lauric acid hydroxylase activities. The steady-state mRNA levels encoding constitutively expressed GST isozymes (Ya1, Ya2, Yb1, Yb2, and Yc1) were decreased by diquat exposure, and the mRNA encoding four of the five constitutively expressed GSTs (Ya1, Ya2, Yb1, and Yc1) were also decreased by ciprofibrate treatment. Nonconstitutively expressed or low constitutively expressed genes (CYP1A1, CYP2B1, CYP2B2, GST Yc2, GST Yf, and UGT1*06) were not induced by exposure to the prooxidants. Changes in isozyme-specific catalytic activities were more consistent with the observed changes in mRNA expression for the GSTs than for the P450s. Both treatments had inhibitory effects on hepatic GSH biosynthesis by decreasing gamma GCS large-subunit mRNA expression, gamma GCS catalytic activities, and hepatic GSH concentrations. Cu/Zn SOD and quinone reductase mRNA levels were increased after ciprofibrate exposure, whereas Cu/Zn SOD mRNA expression was decreased in the diquat-treated animals. The results of this study indicate that diquat and ciprofibrate can decrease the expression profile of a number of phase I, phase II, and antioxidant enzymes and inhibit GSH biosynthesis. These effects may involve the pretranslational loss of hepatic mRNAs, possibly due to accelerated production of reactive oxygen species.

Animals↗

Induction of phase I and phase II drug-metabolizing enzyme mRNA, protein, and activity by BHA, ethoxyquin, and oltipraz.

Various natural and synthetic compounds are known to protect against cancer by elevating phase II detoxification enzymes. Generally classified as monofunctional, these inducers are believed to trigger cellular signal(s) that activate gene transcription through an antioxidant or electrophile response element (ARE/EpRE) in responsive genes. In contrast, the phase I enzymes of drug metabolism (cytochrome P450s) are not believed to be induced by monofunctional inducers and P450 genes have not been found to contain functional ARE/EpREs. In this study, rats were treated with the monofunctional inducers tert-butylated hydroxyanisole, ethoxyquin, and oltipraz to study the inducibility of individual glutathione S-transferase isozymes, NADP(H):quinone oxidoreductase, gamma-glutamylcysteine synthetase, UDP-glucuronosyl transferase, and cytochrome P450 enzymes. Hepatic mRNAs were analyzed on Northern blots using gene-specific oligonucleotide probes for GST Ya1, Ya2, Yc1, Yc2, Yb1, Yb2, and Yf, for UGT 1*06, and for P450 1A1, 1A2, 2B1, 2C11, 3A2, and 4A1. NADP(H):quinone oxidoreductase and gamma-glutamylcysteine synthetase mRNAs were detected using cDNA probes. All the phase II detoxification enzymes analyzed, except GST Yf, were induced by the three monofunctional inducers, suggesting that these genes may be regulated by a mechanism involving an ARE/EpRE element in their promoter region. Interestingly, it was found that ethoxyquin was a particularly good inducer for both members of the P450 2B family, 2B1 and 2B2, and both ethoxyquin and oltipraz were also capable of modestly inducing P450 1A2 and 3A2. Oltipraz was found to slightly induce P450 2B2, but not 2B1, at the dose and time analyzed. Induction of mRNA generally correlated well with induction of protein levels determined by Western blot and/or enzyme activity measurements for selected enzymes. The results of this study suggest that many phase II enzymes may contain ARE/EpRE elements in addition to those confirmed to be regulated by a mechanism involving ARE/EpRE elements. In addition, it was found that several P450 enzymes were induced by monofunctional inducers, suggesting a possibility that some phase I enzymes may also be regulated by a mechanism involving ARE/EpRE elements.

Animals↗

Detection of acute avascular necrosis of the femoral head in dogs: dynamic contrast-enhanced MR imaging vs spin-echo and STIR sequences.

OBJECTIVE: Spin-echo MR imaging has been shown to be highly sensitive in the detection of avascular necrosis. Very early avascular necrosis can, however, appear normal on MR images. We compared dynamic contrast-enhanced MR imaging with conventional spin-echo and short Tl inversion-recovery (STIR) sequences for detecting acute osteonecrosis in an animal model. MATERIALS AND METHODS: Avascular necrosis was induced unilaterally in the femoral heads of five dogs that were imaged with a 1.5-T system within 3 hr of devascularization. After standard T1-weighted, T2-weighted, and STIR images, gradient-recalled echo images, 28/5 (TR/TE) with a 45 degrees flip angle, were obtained at 6-sec intervals for 90 sec synchronous with the IV administration of 0.2 mmol of gadoteridol per kilogram of body weight at a rate of 2 ml/sec via an automated injector. Two animals were reimaged after 7 days. RESULTS: Spin-echo and STIR images did not show any acute changes in the ischemic femoral heads. In contrast, significant differences were present in the enhancement profiles of the marrow spaces in the normal and ischemic femoral heads (p = .005). Normal marrow was characterized by rapid enhancement, with an average signal intensity increase of 83% peaking at 36 sec; no measurable enhancement was seen in the marrow of the ischemic femoral head. Spin-echo images, obtained 7 days after devascularization (n = 2), showed changes characteristic of avascular necrosis. Dynamic contrast-enhanced MR images showed persistent lack of enhancement in the avascular marrow of the ischemic femoral head. A junctional zone, characterized by rapid contrast enhancement in excess of 120% without early washout, was identified at the interface between normal and avascular marrow. CONCLUSION: In this experimental model, dynamic contrast-enhanced MR imaging proved significantly more sensitive than conventional spin-echo and STIR imaging in the detection of acute avascular necrosis.

Acute Disease↗

An unusual presentation of splenic rupture.

A case is described of rupture of the spleen with a hemoperitoneum which was forced through two abdominal wall hernias to produce potentially misleading ecchymosis of the upper midline and the thigh. The diagnostic significance of the entire clinical presentation is discussed.

Hemoperitoneum↗

Evaluating benign breast disease.

Benign breast diseases are present in some form in nearly all women. A basic understanding of breast anatomy and physiology, underlying pathology and methods available for evaluating breast problems provides the ability to assess the client's breast complaint. Four common breast problems--fibrocystic disease, fibroadenoma, mammary duct ectasia, and intraductal papilloma--are described along with guidelines for assessment and referral or follow-up. Current breast-imaging options are discussed in terms of their usefulness and limitations. The value of consumer education regarding benign breast problems cannot be overstated. The National Cancer Institute offers free consumer information explaining benign breast diseases and evaluation techniques.

Adenofibroma↗

Elimination of mechanical failure of the Hickman right atrial catheter.

The double lumen Hickman right atrial catheter (Evermed Co., Palo Alto, Calif.) is usually inserted through an open venous cutdown into the internal jugular or cephalic vein. It is difficult to mechanically secure. Tight ligatures around the vein opening and catheter occlude the lumen of the Silastic rubber catheter while loose ligatures allow slippage. Migration of the tip into the vena cava or innominate vein causes fibrin sleeve formation and occlusion. Because of problems during the initial use of this catheter, we modified a subsequent series by placing a Silastic rubber bead on the catheter. The catheter is carefully trimmed so that the tip will lie in the right atrium and the bead is placed into the vein proximal to the securing ligature. Comparison of the two series of primarily leukemic patients revealed complete elimination of mechanical problems in patients with beaded catheters (0/18), and significant mechanical failure in unbeaded catheters (7/23). These data indicate that adequate fixation of the Hickman catheter at the level of the venotomy and placement of the tip in the right atrium eliminates mechanical failure and markedly improves catheter function.

Adult↗