Effect of timing of prostaglandin administration, controlled internal drug release removal and gonadotropin releasing hormone administration on pregnancy rate in fixed-time AI protocols in crossbred Angus cows.

Two experiments were conducted to investigate the effects of timing of prostaglandin F2(alpha) (PGF2(alpha)) administration, controlled internal drug release device (CIDR) removal and second gonodotropin releasing hormone (GnRH) administration on the pregnancy outcome in CIDR-based synchronization protocols. In Experiment 1, suckled Angus crossbred beef cows (n = 580) were given 100 microg of GnRH+a CIDR on Day 0. Cows in Group 1 (modified Ovsynch-P) received 25 mg of dinoprost (PGF2(alpha)) and CIDR device removal on Day 8 (AM), 100 microg of GnRH 36 h later on Day 9 (p.m.), and fixed-time AI (FTAI) 16 h later on Day 10 (47.5+/-1.1 h after PGF2(alpha)). Cows in Group 2 (Ovsynch-P) received 25mg of PGF2(alpha) and CIDR device removal on Day 7 (p.m.), 100 microg of GnRH 48 h later on Day 9 and FTAI 16 h later on Day 10 (66.6+/-1.2 h after PGF2(alpha)). Pregnancy rates were 56.5% (170/301) for Group 1 and 55.6% (155/279) for Group 2, respectively (P = 0.47). In Experiment 2, beef cows (n=734) were synchronized with 100 microg of GnRH+CIDR on Day 0, 25 mg of PGF2(alpha) and CIDR device removal on Day 7 and either 100 microg of GnRH 48 h later on Day 9 (Ovsynch-P) and FTAI 16 h later on Day 10 (64.9+/-3.3 h from PGF2(alpha)) or 100 microg of GnRH on Day 10 (CO-Synch-P) at the time of AI (63.2+/-4.2 h from PGF2(alpha)). Pregnancy rates were 48.8% (180/369) for Ovsynch-P and 44.7% (163/365) for CO-synch-P groups, respectively (P = 0.11). In both experiments, there was a locationxtreatment interaction (P<0.05); pregnancy rates between locations were different (P < 0.05) in the Ovsynch-P group. In conclusion, in a CIDR-based Ovsynch synchronization protocol, delaying administration of prostaglandin and CIDR removal by 12 h, or timing of the second GnRH by 16 h, did not affect pregnancy rates to FTAI. Therefore, there may be an opportunity to make changes in synchronization protocols with out adversely affecting FTAI pregnancy rates.

Magnetic resonance imaging of muscle electroporation injury.

Low frequency electrical currents traversing the body during electrical shock can produce tissue damage by effects of electrical forces on cellular organelles and proteins as well as by Joule heating beyond thermotolerance. Treatment for these different injuries are quite distinct. Therefore, it is important to accurately diagnose the form of injury. Here we discuss the use of MRI for this purpose.

Selective lymphoscintigraphy: a necessary adjunct to dye-directed sentinel node biopsy for breast cancer?

BACKGROUND: Dye-directed sentinel node biopsy (SNB) for breast cancer provides accurate staging with low morbidity, but for tumors distant from the axilla, its use has been questioned. HYPOTHESIS: Can preoperative breast lymphoscintigraphy (BL) applied selectively to medial hemisphere tumors predict a subset of patients who may not require surgical staging of the axilla? DESIGN: Prospective cohort study. SETTING: Tertiary, multidisciplinary breast center. PATIENTS: Thirty-two women with breast tumors located in the medial hemisphere (30) or inframammary crease (2). INTERVENTION: Peritumoral injection of 500 microCi of technetium Tc 99m sulfur colloid and biplanar imaging. Nonpalpable lesions were localized with ultrasound or mammography. At the time of definitive breast surgery, isosulfan blue dye-directed SNB was performed. Axillary dissection was performed when the SN contained a tumor or could not be identified. MAIN OUTCOME MEASURES: Regional nodal basins identified by BL; success rate of SNB. RESULTS: Preoperative BL demonstrated axillary drainage in 28 patients (88%); 2 patients (6%) had isolated internal mammary radionuclide uptake, and 2 patients had no nodal uptake. Dye-directed axillary SNB succeeded in 27 (87%) of 31 patients, including both patients with failed BL. Breast lymphoscintigraphy had predicted isolated internal mammary drainage in 2 of 4 patients whose SNs could not be identified. Metastases were found in 5 patients (16%). CONCLUSIONS: Axillary radionuclide uptake predicts but does not augment dye-directed SN identification. In those few patients with isolated internal mammary drainage, BL may obviate the need for surgical staging of the axilla.

Antineoplastic agents 430. Isolation and structure of cribrostatins 3, 4, and 5 from the republic of maldives cribrochalina species.

Continued investigation of cancer-cell growth-inhibitory constituents of the blue marine sponge Cribrochalina sp. has led to discovery of cribrostatins 3 (4a), 4 (5), and 5 (4b) in 10(-5) to 10(-7) % of the wet weight. The structure of cribrostatin 3 (4a) was determined by results of high field (500 MHz) (1)H and (13)C NMR and HRMS interpretations. The same general approach to the structures of cribrostatins 4 (5) and 5 (4b) was completed by X-ray crystal structure determinations. Cribrostatins 3, 4, and 5 provided significant cancer cell line inhibitory activities. Cribrostatins 1 and 2(2) and the newly isolated cribrostatins 3-5 displayed antibacterial and/or antifungal activities.

Common bile duct stone characteristics: correlation with treatment choice during laparoscopic cholecystectomy.

Determining the most appropriate management approach for patients with unsuspected choledocholithiasis may be difficult because of the subjective nature of this decision in the absence of clinical data. Treatment of incidental choledocholithiasis during laparoscopic cholecystectomy was reviewed during a 25-month period. Operative cholangiograms were analyzed retrospectively to determine if associations exist between common bile duct stone characteristics and the intraoperative treatment selected by the operating surgeon. Cholangiographic data included quantification of common bile duct stones, stone dimension, position, and presence of radiopaque contrast flow into the duodenum. Two hundred thirty-six laparoscopic cholecystectomy patients underwent operative cholangiography; 25 (11%) demonstrated choledocholithiasis. Seven patients were converted to open common bile duct exploration (group I), 16 patients were referred for postoperative endoscopic retrograde cholangiopancreatography (group II), and two patients were observed (group III). Evaluation of the operative cholangiograms revealed multiple common bile duct stones (>1) in 86% (6 of 7) in group I, 25% (4 of 16) in group II, and none in group III. All patients in group I had at least one stone larger than 5 ml in greatest diameter, whereas only 33% (6 of 18) in groups II and III combined had stones larger than 5 ml. Group I had significantly (P = 0.027) more representation of delayed or no contrast flow during operative cholangiography compared to groups II and III. The intraoperative decision to proceed with laparoscopic cholecystectomy and rely on postoperative endoscopic retrograde cholangiopancreatography for stone retrieval rather than open common bile duct exploration was associated with (1) a single common bile duct stone, less than or equal to 5 ml in size on operative cholangiogram and (2) normal contrast flow into the duodenum. Open common bile duct exploration was more frequently associated with the demonstration of multiple or large (>5 ml) stones. A periampullary stone did not discriminate among treatment choices.

Distributing working versions of published mathematical models for biological systems via the Internet.

Mathematical models are useful tools for investigating complex systems. By representing physiological systems as models, theories can be tested quantitatively against data from the system. Models can be used to explore new theories prior to experimentation and to design studies to optimize experimental resources. They can also be used as teaching tools to illustrate physiochemical principles. In spite of their usefulness and the time invested in developing models, published models are often underused due to the difficulty in obtaining working versions of the model. To address this problem we have designed a library for mathematical models of biological systems on the Internet. The library contains published models of biological systems in formats compatible with several modeling packages, from the fields of physiology, metabolism, endocrinology, biochemistry, and chemistry. The models can be viewed graphically, model solutions can be viewed as plots against data, and models can be downloaded to be run with software on the user's own system. The address of the library is: http://biomodel.georgetown.edu/model/ Investigators are invited to submit working versions of published models to the library. Models can be submitted electronically at the time a manuscript is accepted for publication. As journals go online, articles containing models can be linked to working versions of the models in the library. By increasing access to working versions of models, more of the investment in kinetic studies and model development can be realized.

Partial portacaval shunt for variceal hemorrhage: longitudinal analysis of effectiveness.

OBJECTIVE: To determine rates of survival, long-term patency, and recurrent variceal hemorrhage among patients with alcoholic cirrhosis treated by partial portacaval shunt. DESIGN: Single-institution cohort follow-up study of 72 consecutive patients who underwent small-diameter portacaval H-graft shunt with collateral ablation during a 10-year period (1981 through 1990). Subjects were enrolled and followed up for up to 15 years. Shunt patency was assessed by portography and/or ultrasonography. We performed 7-year Kaplan-Meier analyses of survival (in 65 patients in Child classes A and B), shunt patency, and absence of variceal bleeding. SETTING: Tertiary academic referral center of the US Department of Veterans Affairs. PATIENTS: Patients with alcoholic cirrhosis were considered for operation after at least 1 proven episode of variceal hemorrhage. Patients with portal vein thrombosis were excluded; patients in Child class C underwent operation only for compelling indications. Of the 72 who underwent partial shunting, 38 were in Child class A, 27 were in class B, and 7 were in class C. INTERVENTIONS: Partial portacaval shunt (6-, 8- or 10-mm polytetrafluoroethylene H-graft with collateral ablation) and serial follow-up. MAIN OUTCOME MEASURES: Study end points were death, recurrent variceal hemorrhage, and unavailability for follow-up. Other measures included graft patency and nonvariceal rebleeding. RESULTS: Cumulative probability of 7-year patency for grafts at risk was 95%. The 7-year probability for absence of variceal bleeding in patients at risk was 92%. In 65 patients in Child classes A and B, operative mortality was 7.7% and the cumulative probability of 7-year survival was 54%. CONCLUSION: For variceal bleeding associated with alcoholic cirrhosis, the small-diameter polytetrafluoroethylene portacaval H-graft with collateral ablation affords durable patency and protection against variceal rebleeding.

Modeling of arterial and cardiopulmonary baroreflex control of heart rate.

We evaluated R-R interval changes (delta R-R interval) in 13 subjects (27 +/- 6 yr; 7 men and 6 women) as a function of blood pressure changes at the carotid sinus and aortic arch and central venous pressure changes at the cardiopulmonary receptors. Neck chamber pressure and suction were used to change pressure at the carotid sinus while lower body negative pressure, phenylephrine infusion, and nitroprusside infusion were used to change pressure at the carotid sinus (delta CSP), aortic arch (delta AAP), and cardiopulmonary receptors (delta CPP). Random effects regression analysis showed a significant linear relationship for delta R-R interval (-1.75 + 1.64 delta CSP + 15.40 delta AAP + 29.02 delta CPP + error), and the correlation (r) between the observed and predicted delta R-R interval was 0.82 (P < 0.00001). Sixty-seven percent of the delta R-R interval variability observed in the study is explained by the model. delta AAP accounts for approximately 63%, delta CSP for 14%, and delta CPP for 23% of the explained delta R-R interval.

Managing choledocholithiasis in the laparoscopic era.

BACKGROUND: Management options for common bile duct stones have explained in the era of laparoscopic cholecystectomy (LC), and selecting the most appropriate method for each patient can be problematic due to the difficulty of predicting accurately which patients have choledocholithiasis (CDL). In order to improve selection of appropriate treatment for CDL, treatment options were analyzed for outcome retrospectively during a 25-month period beginning June 1, 1992. PATIENTS AND METHODS: Four hundred four patients underwent LC; 48 (12%) had CDL identified at preoperative endoscopic retrograde cholangiopancreatography (ERCP) or intraoperative cholangiogram (IOCG). Forty-seven patients were referred for preoperative ERCP for suspected CDL, 23 (49%) of whom had proven duct stones and underwent endoscopic sphincterotomy and stone retrieval with an 87% success rate. RESULTS: Of 357 patients scheduled for LC without preoperative ERCP, 236 had IOCG, of which 25 (11%) demonstrated CDL. Seven patients had open common bile duct exploration (CBDE). Sixteen patients had postoperative ERCP after positive IOCG, 7 (44%) of which were positive for CDL and whose stones were removed with 100% success. Two patients were observed, anticipating spontaneous passage of a small stone. CONCLUSIONS: Preoperative ERCP should be applied selectively. For the large majority of patients without preoperative evidence of CDL, we recommend routine IOCG; if CDL is demonstrated, an intraoperative decision can be made to proceed to postoperative ERCP in the usual case or to open CBDE for very large or multiple stones. Observation in anticipation of spontaneous passage may be appropriate for small, solitary common duct stones. Continuing advances in laparoscopic CBDE are likely to reduce further the need to rely on ERCP in managing CDL.

Surgical management of breast masses in pregnant women.

OBJECTIVE: The goal of this study was to review the outcomes of breast biopsies in pregnant women in order to plan optimum management strategies for pregnant women with breast masses. STUDY DESIGN: From January 1990 to October 1992, 17 pregnant women underwent breast biopsy at a university hospital. Parameters evaluated were (1) trimester at presentation, (2) timing of biopsy, (3) mode of anesthesia, (4) requirements for tocolytics, and (5) histology of the lesion. RESULTS: Antepartum biopsy was performed on all 11 patients who presented in the first or second trimester. Biopsy was accomplished postpartum in four of five patients presenting in the third trimester. Only one patient required tocolysis (associated with biopsy followed by immediate mastectomy). Histologic diagnosis was predominantly lactating adenoma (13 of 17 patients). CONCLUSION: These results demonstrate that breast biopsy can be safely performed on pregnant women. We recommend that women presenting with breast masses in the first or second trimester undergo antepartum biopsy. We recommend postpartum excision for masses presenting in the latter half of the third trimester. For those presenting in the first half of the third trimester, fine needle aspiration biopsy may be a suitable alternative, particularly for the mass suspicious for cancer.

Collateral ablation improves portal perfusion after partial portacaval shunt.

Small-diameter portacaval H-grafts (partial shunts) effectively abolish bleeding from esophageal varices. Goals are 1) to prevent variceal hemorrhage by subtotal portal decompression, and 2) to minimize postshunt encephalopathy by maintaining substantial residual pressure and prograde flow in the portal vein. To reduce spontaneous shunting of portal blood away from the liver, we advocate ablation of collateral vessels after partial shunts. Others have performed partial shunts without collateral ablation. We postulated that ablation of collateral vessels would augment portal perfusion pressure and preserve prograde portal flow after partial shunts. In 15 patients undergoing 8 or 10 mm portacaval H-grafts, portal pressure was measured intraoperatively before and after ligation of principal venous collaterals. In another 13 patients, collateral embolization was performed during postoperative portography. The degree of portal perfusion was scored. Pressure measurements demonstrated a mean rise in portal pressure of 2.8 cm saline after ligation (P = 0.025). Angiographic perfusion scores after embolization improved by a mean of 0.57 points on a 4 point scale (P = 0.032). We conclude that intraoperative collateral ligation augments residual portal pressures and that postoperative collateral embolization improves portal flow patterns. Since both observed effects have been associated with decreased postshunt encephalopathy rates, ablation of collateral vessels must be an integral component of the partial portacaval shunt.

Surgical management of portal hypertension.

Portal hypertension is frequently complicated by upper gastrointestinal tract bleeding and ascites. Hemorrhage from esophageal varices is the most common cause of death from portal hypertension. Medical treatment, including resuscitation, vasoactive drugs, and endoscopic sclerosis, is the preferred initial therapy. Patients with refractory hemorrhage frequently are referred for immediate surgical intervention (usually emergency portacaval shunt). An additional cohort of patients with a history of at least 1 episode of variceal hemorrhage is likely to benefit from elective shunt operations. Shunt operations are classified as total, partial, or selective shunts based on their hemodynamic characteristics. Angiographically created shunts have been introduced recently as an alternative to operative shunts in certain circumstances. Devascularization of the esophagus or splenectomy is done for specific indications. Medically intractable ascites is a separate indication for surgical intervention. Liver transplantation has been advocated for patients whose portal hypertension is a consequence of end-stage liver disease. In the context of an increasingly complex set of treatment options, we present an overview of surgical therapy for complications of portal hypertension.

Narrow-diameter portacaval shunts for management of variceal bleeding.

Over the past decade, we have developed and refined a method for partial portosystemic shunting for the control of bleeding esophageal varices in alcoholic cirrhotic patients. The narrow-diameter interposition portacaval H-graft using 8 mm polytetrafluoroethylene has been performed in 32 patients at our institution with low operative mortality (6.3%) and nearly complete cessation of variceal bleeding (96.7%) over a mean follow-up period of 43 months. In comparison with total shunts, diminished rates of postshunt encephalopathy (13% versus 40%) have been observed. Prograde portal blood flow has been preserved in 90% of 30 patients studied by perioperative portography. Shunt patency with continued prograde flow has been demonstrated at up to 9 years of follow-up. Investigators at three other centers have studied partial shunting using substantially similar techniques, with similar findings. Based on these results, we conclude that narrow-diameter shunts provide effective, long-lasting treatment for variceal hemorrhage due to portal hypertension in the alcoholic.