A novel early-stage orthotopic model for ovarian cancer in the Fischer 344 rat.

The purpose of our study was to ascertain the progression of metastases in a novel ovarian cancer model designed to mimic early-stage disease by utilizing an orthotopic injection technique. Female Fischer 344 rats were injected with either 10(4) or 10(5) NuTu-19 cells by intraperitoneal or orthotopic injection. Peritoneal washings and histologic specimens were examined to correlate the incidence and extent of tumor growth. In a second phase, orthotopic injections of 10(2) and 10(3) cells were compared to that of 10(4) cells. Progression of ovarian cancer was observed by gross and microscopic examinations in both intraperitoneal and orthotopic models. Pelvic extension and abdominal adhesions uniquely characterized the orthotopically injected animals. Numbers of identifiable metastases declined with lower cell inocula, confirming that early-stage disease was extended to at least 14 days with 10(2) NuTu-19 cells. The orthotopic ovarian cancer model emulates early disease with the initiation of a primary tumor that is localized within the inherent microenvironment. The orthotopic model offers a clinically relevant alternative for future cancer research that allows for the investigation of therapeutic strategies against early stages of the disease process.

Increased transperitoneal bacterial translocation in laparoscopic surgery.

BACKGROUND: The indications for laparoscopic surgery have expanded to include diseases possibly associated with peritonitis such as appendicitis, perforated peptic ulcers, and diverticulitis. The safety of carbon dioxide (CO2) pneumoperitoneum in the presence of peritonitis has not been proved. Our previous investigations demonstrated increased bacteremia associated with CO2 insufflation. In effort to clarify the relative effects of intraabdominal pressure and type of gas, this study was designed to measure bacterial translocation with different gases at different pressures of pneumoperitoneum. METHODS: For this study, 110 rats were given intraperitoneal bacterial innoculations with Escherichia coli and equally divided into five groups of 20 animals each. The study groups included a control group with no pneumoperitoneum administered (n = 30), insufflation at a commonly used pressure of 14 mmHg with helium (n = 20) and CO2 (n = 20), and low insufflation at 3 mmHg with helium (n = 20) and CO2 (n = 20) in an effort to minimize influences related to pressure. Blood cultures were checked at 15-min intervals for the first 45 min, then hourly thereafter for a total of 165 min after peritoneal inoculation with 2 x 10(7) E. coli. RESULTS: There is increased risk of bacterial translocation in comparing groups that underwent pneumoperitoneum with those that did not in the rat peritonitis model. Furthermore, these findings are dependent on the presence or absence of gas, but not necessarily on the type of gas used for insufflation. In the low-pressure groups of both gases (helium and CO2), bacterial translocation was significantly increased, as compared with the control group. Low pressure also was associated with increased bacterial translocation, as compared with high pressure, but beyond 30 min of insufflation, no significant differences were apparent. CONCLUSIONS: The risk of bacterial translocation in the E. coli rat peritonitis model is increased with insufflation using CO2 or helium, and this effect is more significant at lower pressures (3 mmHg) than at higher pressures (14 mmHg). However, no clinically applicable conclusions regarding the relative effects from type of gas or insufflation pressures could be confirmed.

Tetracycline delivery from fibrin controls peritoneal infection without measurable systemic antibiotic.

The addition of antibiotics to an adhesive haemostat results in an ideal system for the treatment of a localized infectious disease. Fibrin sealant (FS) is a biocompatible, resorbable, adherent haemostat that can deliver antibiotics. Previous use of fibrin to deliver antibiotics resulted in rapid release and limited bioactivity. We have reported previously that poorly soluble antibiotics significantly retard release from FS, resulting in extended delivery in vitro, and overcome antibiotic-resistant infection. We now report that localized antibiotic delivery from FS controls peritoneal infection without measurable systemic antibiotic. Rats and mice were implanted with preformed FS discs containing tetracycline free-base to evaluate control of peritoneal sepsis and to measure serum tetracycline levels. Infection was initiated with Staphylococcus aureus. Morbidity and mortality were evaluated for 14 days. Serum was isolated from jugular vein blood with subsequent evaluation for antimicrobial activity. Mice prophylactically treated with FS-tetracycline (FS-TET) 500 mg/kg 2 days before infection cleared the S. aureus infection, resulting in 100% survival. Mice treated with FS-TET 500 mg/kg 7 days before infection survived. Mice treated with FS-TET 1750 mg/kg 35 days before infection also survived. Rats treated with FS-TET 500 mg/kg had undetectable serum tetracycline levels, whereas in vitro release of tetracycline from FS-TET pellets in rat serum was readily detected. We conclude that fibrin is an excellent vehicle for extended delivery of low solubility tetracycline. Tetracycline delivered from FS is an appropriate chemotherapy for S. aureus peritonitis. FS-TET controls localized infection without a measurable concentration of systemic tetracycline.

The role of AT1 angiotensin receptor activation in the pathogenesis of preeclampsia.

OBJECTIVES: Preeclampsia is characterized by an increase in vascular tone associated with reduced uteroplacental flow. The nature of hypertension arising in pregnancy suggests that the abnormal increase in blood pressure is dependent on some humoral factor that mediates vasospasm. There is evidence that preeclampsia results from a breakdown in the balance between vasodilators such as prostacyclin and prostaglandin E2 and nitric oxide and the vasoconstrictors angiotensin II, thromboxane A2, serotonin, and endothelin. Furthermore, vascular reactivity to angiotensin II is greatly enhanced in preeclampsia as opposed to normal pregnancies. The increased vascular tone and the enhanced thromboxane production noted in preeclampsia may be mediated by the increased sensitivity to angiotensin II because angiotensin II coupled to an AT1 receptor is a potent vasoconstrictor and stimulates the accumulation of free arachidonic acid, the precursor of thromboxane and the prostaglandins. STUDY DESIGN: We used a rat model that has been shown to express the relevant clinical features of human preeclampsia to investigate the involvement of the AT1 angiotensin receptor in this pathologic condition. Pregnant rats were divided into three groups that were either infused with saline or endotoxin on the 14th day of pregnancy. One of the endotoxin-infused groups was further treated with the AT1-selective antagonist losartan from day 11 until day 19 of pregnancy. RESULTS: Perinatal outcome, blood pressure, and urine protein were monitored for each group. We observed that endotoxin infusion resulted in a decrease in pup weight and number of pups and caused an increase in mean arterial pressure as well as increased proteinuria when compared with saline solution-infused animals. In contrast, endotoxin-infused rats receiving losartan exhibited no change in number or weight of pups when compared with control, and losartan tended to diminish the rise in mean arterial pressure. In addition, the increase in urinary protein excretion was completely blocked by losartan. CONCLUSIONS: Endotoxin infusion in pregnant rats appears to be a suitable model for the study of preeclampsia. Moreover, the angiotensin II-dependent activation of an AT1 receptor appears to mediate a portion of the pathophysiologic features associated with preeclampsia.

Psychoanalytic interpretation of the Rorschach: do we have better hieroglyphics?

Schafer (1954) advanced the "Psychoanalytic Interpretation in Rorschach Testing" and asserted that thoughtful interpretation involved more than translating hieroglyphics or scores. In this book, he presented his thesis by describing four defensive styles (repression, denial, projective, and obsessive-compulsive) at various levels of severity of psychopathology. To investigate whether the Structural Summary data from Exner's (1986) Comprehensive System, with its improved reliability and validity and additional scores, allow one to make similar distinctions among the types of defense and severity of disturbance, we rescored the Schafer records. The results of this conservative test of Exner's system suggest that (a) the Comprehensive System reliably distinguishes the repressive style from the other styles, and (b) scores alone may provide adequate measures of severity of disturbance even with form quality excluded. We concluded that Rorschach scores must be understood as complex products of multiple psychological operations and may correspond to different subjective experiences in various contexts.

Usefulness of structural Rorschach data in identifying inpatients with depressive symptoms: a preliminary study.

To explore the usefulness of various structural Rorschach data in identifying psychiatric inpatients with symptoms of depression, 54 adult inpatients were administered a Rorschach. Results indicated that the Comprehensive System, Rorschach Depression Index did not identify many of these individuals as depressed, but did identify most of the extratensive depressed individuals. Each variable included in the Depression Index and other potential, Rorschach correlations of depression were also investigated. Most of them were found to occur more often among these depressed patients than among nonpatients. Furthermore, adding other variables and using more liberal cutoffs may result in more accurate identification of patients with depressive symptoms.

The reliability of Rorschach variables for inpatients presenting symptoms of depression and/or helplessness.

Fifty newly admitted patients presenting symptoms of depression and/or helplessness were recruited to participate in a study concerning depression and randomized into two groups. Rorschachs were administered shortly after admission and then three or four days later. The subjects in the experimental group were instructed to give responses different than they had in the first test. Approximately two-thirds of the responses given by the experimental group in test 2 were different from those in test 1, whereas the control subjects repeated 66% of their test 1 answers in test 2. Retest correlations for 28 variables critical to interpretation show that the two groups differed significantly for four. The retest correlations for four of five variables often used as indices of depressive features were significantly high for both groups. Unusual findings are noted in the retest correlations for FM and m for the Control group and questions are raised concerning the modest retest correlations for CF and C + Cn versus the more commonplace summation of CF + C.