Novel combinations of vancomycin plus ceftaroline or oxacillin against methicillin-resistant vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA.

We demonstrated a significant inverse correlation between vancomycin and beta-lactam susceptibilities in vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) isolates. Using time-kill assays, vancomycin plus oxacillin or ceftaroline was synergistic against 3 of 5 VISA and 1 of 5 hVISA isolates or 5 of 5 VISA and 4 of 5 hVISA isolates, respectively. Beta-lactam exposure reduced overall vancomycin-Bodipy (dipyrromethene boron difluoride [4,4-difluoro-4-bora-3a,4a-diaza-s-indacene] fluorescent dye) binding but may have improved vancomycin-cell wall interactions to improve vancomycin activity. Further research is warranted to elucidate the mechanism behind vancomycin and beta-lactam synergy.

Using a belly board device to reduce the small bowel volume within pelvic radiation fields in women with postoperatively treated cervical carcinoma.

OBJECTIVE: The purpose of this study was to attempt to reduce the small bowel volume in cervical cancer patients undergoing radiation therapy using the belly board device and a four-field technique. METHODS: From 1994 through 1997, twenty-one patients with cervical cancer were referred to the University of Minnesota Medical Center and underwent surgical staging with or without radical hysterectomy followed by postoperative external beam radiotherapy for various indications including positive nodal disease (n = 11), lymph-vascular space invasion (n = 2), poor histology (n = 3), parametrial disease (n = 4), and positive vaginal margin (n = 1). RESULTS: The median age of the 21 patients was 42 years (25-54 years) and a median external beam pelvic radiation dose of 4775 cGy (range, 4200-5075 cGy) was administered. All patients were evaluated for amount of small bowel in the field in both the supine and prone positions, with and without the belly board device (BBD), using a four-field technique. With a full bladder, abdominal radiographs with contrast were obtained to evaluate the volume of small bowel within the radiation fields. In most patients, the BBD was effective at minimizing the amount of small bowel in the lateral fields, whereas a prone position on the treatment table (without the BBD) spared the most small bowel with the AP/PA fields. Therefore over a 2-day cycle, the most small bowel sparing was obtained with the patients treated prone on the BBD for the lateral fields on Day 1 and prone on the table for the AP/PA fields on Day 2. Patients had FIGO stage IB (n = 18), IA2 (n = 1), and IIA (n = 2). The median follow-up was 37 months (24-65 months). No significant acute gastrointestinal or genitourinary toxicity was experienced and no patients have experienced a bowel obstruction to date. CONCLUSIONS: The BBD may offer a means for positioning the mobile small intestine out of the radiation field and improving the tolerance of radiotherapy. The BBD provides a noninvasive technique for reduction of acute and chronic gastrointestinal morbidity.

The implementation of critical pathways in gynecologic oncology in a managed care setting: a cost analysis.

OBJECTIVES: The aim of the study is to determine whether critical pathways can be implemented at an academic institution to limit cost, without compromising patient satisfaction and quality of care. PATIENTS AND METHODS: Patients undergoing a hysterectomy with either cervical or endometrial cancer were placed on specific critical pathways consecutively for an 18-month study period. Preoperative teaching was intensified to educate the patient regarding expectations during the postoperative period. All patients were started on early feeding and patients were also placed on separate care pathways addressing pain and deep vein thrombosis prophylaxis. Total direct costs and patient satisfaction were obtained throughout the study period. During the year prior to care pathway implementation, patient data and direct costs were obtained for the preintervention group utilized for comparison. Postintervention groups were summarized every 6 months during the study period. RESULTS: From January 1997 through June 1998, 63 patients with cervical carcinoma undergoing a radical hysterectomy (DRG 353) and 21 patients with endometrial cancer who underwent a hysterectomy and lymph node sampling (DRG 355) were utilized as the preintervention group. During the 18-month study period (July 1998-December 1999), 42 patients (DRG 353) and 25 patients (DRG 355) were accrued. The average length of stay was reduced from 5.2 (DRG 353) and 4.7 days (DRG 355) prior to implementation of pathways to 3.4 days in both groups. In addition, total direct costs were reduced by 29 (DRG 353) and 32% (DRG 355) after implementation of care pathways. Patient satisfaction data recorded during the study did not demonstrate any change throughout the study period nor were there any higher rates of readmission after implementation of the care pathways. CONCLUSIONS: Critical pathways in gynecologic oncology can be implemented in a managed care environment in order to maintain high quality of care, maintain outcomes, and help reduce costs.

Morphologic characterization of the ice worm Mesenchytraeus solifugus.

Ice worms occupy a unique position in metazoan phylogeny in that they are the only known annelid that completes its life cycle in ice. The mechanism(s) associated with this adaptation are likely to occur at different levels, ranging from modification of their metabolism to changes in morphology. In this study, we examined specimens of Mesenchytraeus solifugus by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) in an effort to identify morphologic structures that may aid in its glacial habitation. We report that M. solifugus contains an elongated head pore at the tip of its prostomium, numerous sensory structures, and differentially oriented setae that curve abruptly at their distal end.

Expression of complement regulatory proteins-CD 35, CD 46, CD 55, and CD 59-in benign and malignant endometrial tissue.

OBJECTIVE: Complement system plays an important role in host defense mechanisms against microorganisms and tumor cells. To protect themselves from autologous complement-mediated damage, normal host tissues express cell membrane-associated complement regulatory proteins (CRPs). To investigate whether neoplastic endometrial tissues overexpress these proteins to escape complement damage, we examined the distribution of complement receptor type 1 (CR1, CD35), membrane cofactor protein (MCP, CD46), decay-accelerating factor (DAF, CD55), and protectin (MACIF, CD59) on frozen endometrial tissue samples. METHODS: A total of 54 endometrial tissue samples were collected. Cryosections were obtained of 31 benign and 23 malignant tissue specimens. Tissue sections were stained by immunohistochemical staining procedure using specific antibodies and employing the avidin-biotin technique. Quantitation of the protein content of these CRPs was determined using the Samba 4000 image analysis system. RESULTS: For all four of the CRPs studied, a statistically significant difference in protein expression between the benign and malignant endometrial tissue specimens (P < 0.0001) was observed. CONCLUSIONS: Overexpression of all the CRPs studied (CD35, CD46, CD55, CD59) was observed in the malignant as compared with the benign endometrial tissues. The upregulation of these CRPs may promote resistance of the endometrial malignant tissue to complement-mediated damage, thereby allowing the tumor cells to escape from cytolysis and thus promoting carcinogenesis.

Clinical pathway implementation improves outcomes for complex biliary surgery.

BACKGROUND: Complex biliary surgery is associated with significant morbidity, prolonged hospital stay, and high cost. Clinical pathway implementation has the potential to standardize treatment and improve outcomes. Therefore the aim of this analysis was to determine whether clinical pathway implementation and/or feedback of outcome data would alter hospital stay, charges, and mortality rates for complex biliary surgery at an academic medical center METHODS: Pre- and postoperative length of stay, hospital charges, and mortality rates were monitored for 36 months before (period 1) and for 2 18-month periods (periods 2 and 3) after implementation of a clinical pathway for hepaticojejunostomy. Outcome data were provided to the surgeons 18 months after pathway implementation to determine whether further clinical practice improvement was possible. RESULTS: From 1991 to 1997, 339 patients underwent hepaticojejunostomy at The Johns Hopkins Hospital for malignant and benign biliary obstruction. Total length of stay was 13.3 +/- 0.9 days for period 1 compared with 12.5 +/- 0.8 days for period 2 (not significant) and 10.1 +/- 0.3 days for period 3 (P < .01 vs period 1; P < .03 vs period 2). Hospital charges averaged $24,446 during period 1 compared with $23,338 during period 2 and $20,240 during period 3 (P < .01 vs periods 1 and 2). Hospital mortality rate was 4.5% during period 1 compared with 0.7% during periods 2 and 3 (P < .05). CONCLUSIONS: These data suggest that implementation of a clinical pathway for hepaticojejunostomy reduces hospital mortality rates and that feedback of outcome data to surgeons results in further clinical practice improvement. Thus clinical pathway implementation and feedback are effective methods to control costs at an academic medical center.

Iron deficiency enhances cholesterol gallstone formation.

BACKGROUND: Cholesterol gallstones occur most commonly in multiparous women, but the causes for this phenomenon remain unclear. This same patient population is prone to chronic iron deficiency anemia. In addition, iron is known to play an important role in hepatic enzyme metabolism. Therefore, we tested the hypotheses that iron deficiency would alter hepatic cholesterol metabolism and enhance gallstone formation. METHODS: Forty adult prairie dogs were fed either a control iron-supplemented (200 ppm), an iron-deficient (8 ppm), a 0.4% cholesterol iron-supplemented (200 ppm), or a 0.4% cholesterol iron-deficient (8 ppm) diet. After 8 weeks gallbladder bile, serum, and liver were harvested. Gallbladder bile was examined for cholesterol crystals and gallstones. Bile lipids and hepatic enzymes were measured, and a cholesterol saturation index (CSI) was calculated. RESULTS: Animals receiving the iron-deficient diet were more likely to have cholesterol crystals in their bile than were animals on the control diet (80% vs. 20%; p < 0.05). Animals on the 0.4% cholesterol iron-deficient diet had more cholesterol crystals per high-powered field (79 +/- 10 vs. 49 +/- 9; p = 0.07), a higher molar % cholesterol (6.0 +/- 0.3 vs 4.4 +/- 0.5; p < 0.05), and a higher CSI (1.27 +/- 0.10 vs. 0.91 +/- 0.07; p < 0.05) compared to animals receiving the 0.4% cholesterol iron supplemented diet. The 7 alpha-hydroxylase levels were lower in the animals on the iron-deficient diet compared to those receiving the control diet (0.42 +/- 0.08 vs 1.17 +/- 0.40 pmol/mg per minute; p = 0.07). CONCLUSIONS: These data suggest that an iron-deficient diet (1) alters hepatic enzyme metabolism, which, in turn, (2) increases gallbladder bile cholesterol and promotes cholesterol crystal formation. We conclude that iron deficiency plays a previously unrecognized role in the pathogenesis of cholesterol gallstone formation in women.

Conservative management of chemotherapeutic-induced thrombocytopenia in women with gynecologic cancers.

During the course of four recent dose-intense chemotherapy trials, the routine practice of transfusing patients with platelet counts < 20,000/microliters was changed to a more conservative style of management limiting prophylactic transfusions to patients with platelet counts < 5000/microliters. One hundred seventy-nine episodes of thrombocytopenia in 46 patients enrolled in four dose-intense chemotherapy trials were evaluated. Thirty-two patients had advanced carcinoma of the ovary, 10 had pelvic sarcomas, and 4 had cervical cancer. Of the 179 episodes of thrombocytopenia evaluated, 100 exhibited severe thrombocytopenia (platelet count < 20,000/microliters). Of these 100 episodes, 30 received prophylactic platelet transfusions while 70 did not. Thirty-eight episodes of thrombocytopenia were 5000-10,000/microliters, 24 of which received prophylactic platelet transfusions while 14 did not. Eighteen episodes (10%) of thrombocytopenia resulted in minor bleeding and all occurred during severe thrombocytopenia. Minor bleeding occurred in 27% of episodes of severe thrombocytopenia receiving prophylactic platelet transfusions versus 14% not transfused (P = 0.2). Of the 38 episodes of thrombocytopenia 5000-10,000/microliters, minor bleeding occurred in 17% receiving prophylactic platelet transfusions versus 24% not transfused (P = 0.95). None of the 179 episodes of thrombocytopenia resulted in major bleeding, including 70 episodes of thrombocytopenia < 20,000/microliters not receiving prophylactic platelet transfusions which included 14 episodes of thrombocytopenia between 5000-10,000/microliters. In conclusion, in women with gynecologic cancer and chemotherapy-induced thrombocytopenia, we safely limited prophylactic platelet transfusions for episodes of thrombocytopenia < 5000/microliters. We hope our study will prompt prospective, randomized trials evaluating the need of prophylactic platelet transfusions for chemotherapy-induced thrombocytopenia in patients with solid tumors.