Modeling of relationships between pharmacokinetics and blockade of agonist-induced elevation of intraurethral pressure and mean arterial pressure in conscious dogs treated with alpha(1)-adrenoceptor antagonists.

Fiduxosin is a new alpha(1)-adrenoceptor antagonist targeted for the treatment of symptomatic benign prostatic hyperplasia. The purpose of this study was to determine and compare the potencies of the alpha(1)-adrenoceptor antagonists terazosin, doxazosin, tamsulosin, and fiduxosin, based on relationships between plasma drug concentrations and blockade of phenylephrine (PE)-induced intraurethral (IUP) and mean arterial pressure (MAP) responses after single oral dosing in conscious male beagle dogs. Magnitude of blockade and plasma concentrations were evaluated at selected time points over 24 h. All drugs produced dose-dependent antagonism of PE-induced IUP and MAP responses. When IUP and MAP blockade effects were plotted against drug plasma concentrations, direct relationships were observed that were well described by the sigmoidal maximal effect model. IUP IC(50) values for terazosin, doxazosin, tamsulosin, and fiduxosin were 48.6, 48.7, 0.42, and 261 ng/ml, respectively. MAP IC(50) values were 12.2, 13.8, 1.07, and 1904 ng/ml, respectively. Uroselectivity index values, defined as MAP IC(50)/IUP IC(50), were 0.25, 0.28, 2.6, and 7.3, respectively. These results extend previous observations with terazosin in this model, showing that doxazosin exhibits a uroselectivity index comparable to terazosin, consistent with the lack of alpha(1)-adrenoceptor subtype selectivity or uroselectivity of these drugs. Tamsulosin, an alpha(1a)-/alpha(1d)-subtype selective agent, had an index value approximately 10-fold greater than the nonselective drugs. Based on its pharmacokinetic profile and a relative uroselectivity 29-fold greater than the nonselective drugs, fiduxosin is expected to exhibit greater selectivity for urethral compared with vascular alpha(1)-adrenoceptors in human and should be a novel, long-acting, uroselective alpha(1)-adrenoceptor antagonist.     

Diet and premenopausal bilateral breast cancer: A case-control study

We investigated associations between diet and premenopausal bilateral breast cancer in a familial matched case-control study. We studied 140 cases from population-based registries in Los Angeles County (California) and Connecticut, and from the major hospitals in the southern parts of the Province of Quebec. Unaffected sisters of the cases served as matched controls (222 total). Dietary intake were assessed with a food frequency questionnaire. Total fat, monounsaturated fat, polyunsaturated fat, oleic acid, and linoleic acid intake was inversely associated with premenopausal bilateral breast cancer risk. Consumption of carbohydrates (and sweetened beverages) was associated with an increased risk. We observed no associations for dietary fiber, antioxidants, or major food groupings, but we did observe inverse associations for intake of low fat dairy products and tofu. These findings suggest that monounsaturated and polyunsaturated fats, as well as soy foods, might reduce the risk of premenopausal bilateral breast cancer.     

Chirurgie der differenzierten Schilddrüsenkarzinome

Die 5-Jahres-überlebensrate von differenzierten Schilddrüsenkarzinomen ist generell sehr gut und betr?gt 80 – 95%. Hierbei bestehen Abh?ngigkeiten zum Alter des Patienten [15], zum prim?ren Tumorstadium, zur histologischen Differenzierung und zum Ausma? der region?ren und Fernmetastasierung [6]. Patienten mit Tumorfreiheit haben ebenfalls eine bessere Prognose gegenüber denen mit einem Resttumor. Dies spricht für ein konsequentes Vorgehen beim Prim?reingriff mit Thyreoidektomie und Entfernung der Lymphknoten des zentralen Kompartments. Stadienadaptiert schlie?t sich eine Radiojodtherapie oder die Kombination mit einer externen Radiatio an. Bei der Reoperation differenzierter Schilddrüsenkarzinome mu? zwischen der individuellen Prognose des Patienten, dem Ziel der Operation und der postoperativen Morbidit?t/Mortalit?t entschieden werden. Aufgrund des hohen Risikos sollten diese Operationen in Zentren durchgeführt werden, so da? postoperative Komplikationen (permanente Recurrensparese/Hypoparathyreoidismus) vertretbar gering gehalten werden k?nnen (Tabelle 11). Dennoch sollte nicht au?er Acht gelassen werden, da? individuell bei differenzierten Schilddrüsenkarzinomen im Stadium pT1 auch ein eingeschr?nkt radikales Vorgehen (Hemithyreoidektomie) ohne Verschlechterung der Prognose m?glich scheint. Strenge Nachuntersuchungsergebnisse und Ergebnisse weiterer klinischer Studien müssen hierzu abgewartet werden.     

Chaos and predicting varix hemorrhage

Despite a wide array of mechanisms implicated in esophagogastric varix hemorrhage, predicting the onset of bleeding or even identifying the dominant factor in its causation has proved elusive. In this article we re-examine variceal pathophysiology and hypothesize that bleeding is rooted in turbulent portal system flow, a phenomenon embodied in the 'new' science of chaos and the principles of non-linear, rhythmic fluid dynamics. Analogous to forecasting the weather, predicting turbulent flow hinges on defining the initial physical conditions, and, like the field theory of quantum physics, depends on probabilities and instabilities rather than direct proportional analysis. Based on the complex regional and systemic hemodynamic forces and local physical properties underlying formation and perpetuation of esophagogastric varices, we propose, as with climatologic events, that a relatively minor or remote physiologic adjustment may set into motion a sequence of destabilizing splanchnic blood flow kinetics that ultimately causes a varix to erupt. In other words, the onset of varix bleeding derives from a sudden, erratic switch from disorganized but stable to disruptive turbulent variceal blood flow, and as a 'chaotic' phenomenon, is likely to remain for the foreseeable future highly unpredictable.     

Occurrence of quinolone resistance in Staphylococcus aureus from nosocomial infection.

Among 63 Staphylococcus aureus isolates (one isolate per one patient) counted from infections (from August to November 1991) in hospital T., eight exhibited resistance to fluoroquinolones. Seven of these quinolone-resistant isolates were multiply- and methicillin-resistant S. aureus (QR-MRSA). The results of phage-, plasmid- and genotyping (pulsed field electrophoresis) revealed that six different strain-clones of these MRSA were spread in the hospital. In vitro spontaneous mutants resistant to fluoroquinolones are 10-100-fold more frequent in MRSA than in other S. aureus when selected on isosensitest-agar containing 1 microgram/ml of ciprofloxacin. However, the same mutant frequencies were found in strain 8325-4 with and without the mecA-determinant. The resistance phenotype was stable over 30 generations of subculture in nutrient broth as well in natural quinolone resistant MRSA as in mutants of other types of S. aureus selected in vitro. The phenotypic association of quinolone resistance and MRSA is rather likely due to a higher frequency of spontaneous resistant mutants which are present in natural populations of MRSA. Data of chemotherapy prior to the isolation of S. aureus show that three of seven patients from whom QR-MRSA were isolated were treated with a quinolone. In eight cases of infections with non-MRSA and quinolone treatment the isolated S. aureus strains were in vitro sensitive to quinolones.     

False-Positive Computed Tomographic Findings in a Series of 525 Patients with Acoustic Neuromas

In our series of 525 patients operated on for acoustic neuroma, there were three false-positive computed tomography findings resulting in unnecessary surgery. The histories and results of laboratory investigations and surgery are presented. Discussion of the outcome had gadolinium-enhanced magnetic resonance imaging been performed is presented.     

Effects of Rapid Increases of Desflurane and Sevoflurane to Concentrations of 1.5 MAC on Systemic Vascular Resistance and Catecholamine Response during Cardiopulmonary Bypass

Background: Airway irritation was hypothesized to trigger the transient cardiovascular stimulation associated with desflurane. The authors administered desflurane during cardiopulmonary bypass (CPB), thus avoiding airway contact, and compared the effects of rapid increases of desflurane to 1.5 MAC on systemic vascular resistance index (SVRI) and catecholamine response to those of 1.5 MAC sevoflurane.

Methods: Forty-eight patients, undergoing elective coronary bypass surgery, were randomly allocated to receive either desflurane or sevoflurane during hypothermic (32-33 [degree sign] Celsius) nonpulsatile CPB at exhaust gas concentrations of 1.5 MAC for 15 min. SVRI was calculated at baseline, 1, 2, 3, 4, 5, 7, 9, 12, and 15 min after starting volatile anesthetics' delivery. Plasma catecholamine concentrations were determined in 12 desflurane-treated patients and 12 sevoflurane-treated patients at baseline, 5, and 15 min.

Results: The time-course of Delta SVRI, (changes in SVRI from baseline), from baseline to 5 min was significantly different between desflurane- and sevoflurane-treated patients, whereas there was no difference from 7 to 15 min. In the desflurane group, SVRI from 1 to 7 min remained unchanged to baseline level, thereafter declining to significantly lower values at 9, 12, and 15 min compared with values from 0 to 5 min, whereas sevoflurane produced an immediate and significant reduction in SVRI. With desflurane, catecholamine concentrations remained unchanged to baseline level at 5 and 15 min; with sevoflurane, they decreased with time.     

Epidemiology of AIDS in Florida.

Florida is third in the nation in the cumulative number of AIDS cases. The epidemic in the state has grown steadily since 1981, clustering initially in metropolitan South Florida but dispersing to other urban and nonurban areas. Heterosexually transmitted AIDS is fast increasing and is more than twice as common in Florida than the United States; however, homosexual/bisexual men and intravenous drug-using men and women continue to represent the majority of new cases. Special serologic studies of the prevalence of HIV infection provide a timely view of the dynamics and characteristics of the epidemic in various segments of the state's population. Data from a large, ongoing serosurvey suggest that about one in every 220 childbearing women is HIV-infected, a finding consistent with Florida's rank of second nationally in the number of pediatric AIDS cases.     

Liver resection without hilus preparation and with selective intrahepatic hilus stapling for benign tumors and liver metastasis

Background Nowadays, liver resection is a routine operative procedure in surgical centers, and strategies must be aimed at avoiding additional risk factors. Extrahepatic isolation of portal vein, hepatic artery and hepatic duct, as well as lymphadenectomy of the liver hilum are generally accepted steps of liver resection, even for metastatic and benign indications. Our primary aim was to analyze the feasibility, blood loss, blood transfusion requirements, incidence of complications, and outcome using the approach for intrahepatic devascularization leaving the extrahepatic hilus untouched. Materials and methods Thirty-eight consecutive patients with resection for metastases and benign liver tumors were selected. After hilar examination, the extrahepatic structures remain intact, and during parenchyma dissection, the whole right or left or the appropriate bi-segmental pedicle is isolated intrahepatically and then transected using a stapler device. Results The used technique was feasible in all cases, and no intra- or postoperative surgical complications were observed. To date, no tumor recurrence was found in the hilum during the follow-up period. Conclusion The intrahepatic pedicle stapling technique appears to be feasible and safe in liver resection. Hilar dissection can, thus, be avoided in liver metastasis and benign liver tumors.