Initial ethanol exposure results in decreased heart rate variability in ethanol-naive rhesus monkeys.

Ethanol's effects on heart rate variability may contribute to the increased cardiac disease and mortality observed in alcoholics. We assessed cardiac response to ethanol in seven previously ethanol-naive monkeys given a standard dose of ethanol, or saline. Ethanol exposure reduced cardiac signal complexity [mean+/-S.D. (ethanol: Hurst parameter=0.39+/-0.02; saline: Hurst parameter=0.32+/-0.06)] and increased the spectral exponent (ethanol: beta=1.36+/-0.35; saline: beta=1.12+/-0.35) when compared to saline, while heart rate itself was unaffected (saline: interbeat interval=303.57+/-24.57; ethanol: interbeat interval=308.14+/-20.45). Taken together with data that show autonomic disregulation in alcoholics, these findings provide further evidence of deleterious ethanol effects on cardiac signal dynamics.     

Ethanol Exposure Results in a Transient Decrease in Human Platelet cAMP Levels: Evidence for a Protein Kinase C Mediated Process

At concentrations between 2 and 32 mM, ethanol is shown to depress human platelet cAMP levels. The effect is biphasic, maximal at 30 sec, with platelet concentrations of cAMP returning to baseline values at higher ethanol concentrations and at longer incubation times. The cAMP lowering effect of ethanol can be blocked by a phosphodiesterase (PPDE) inhibitor, 3-isobutyl-1-methyl-xanthine (IBMX), at a concentration of 2 mM, suggesting that an increase in PPDE activity may be responsible for this effect. Exposure of platelets to 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), a protein kinase C (PKC) inhibitor, blocks the ethanol-induced decrease in platelet cAMP, suggesting ethanol may be acting through activation of PKC.     

Histopathologic score predicts recurrence free survival after radical surgery in patients with stage IA2-IB1-2 cervical carcinoma

BACKGROUND: The authors evaluated clinical and pathologic factors that predicted for recurrence after patients underwent radical surgery for International Federation of Gynecology and Obstetrics (FIGO) Stage IA(2)-IB(1-2) cervical carcinoma and developed a simple method of scoring those predictive factors to quantify outcome. METHODS: An analysis was conducted of a prospective radical surgery cervical carcinoma data base. A Cox proportional hazards regression analysis was done for each of the individual factors to estimate individual risk ratios using all available data for each factor. Stepwise and best-model options were used to identify the best combinations as predictors and to calculate adjusted risk ratios. Based on the information obtained, each patient was assigned a categorical score to predict recurrence. The variables used for the score were dichotomized. The differences between the scores in time to recurrence were evaluated using the log-rank test to compare the time to recurrence curves that were generated with the Kaplan-Meier method. RESULTS: Eight hundred seventy-one patients were included in the study, and 66 patients who developed recurrent disease after a median follow-up of 49 months. Tumor size, maximum depth of invasion, pelvic lymph node status, tumor grade, and capillary lymphatic space (CLS) were single predictors for recurrence, and the score, which was based on combinations of these factors, predicted the disease free survival. Maximum depth of invasion, pelvic lymph node status, and CLS were the best combined predictors for recurrence, and they were used to form a second, precise scoring system to predict disease free survival (P < 0.0001; log-rank test). CONCLUSIONS: The scoring system based on maximal depth of invasion, CLS, and pelvic lymph node metastases identified four strata of patients with distinct recurrence free survival. The incremental presence of each factor decreased recurrence free survival after patients underwent radical surgery. Patients with the presence of all three factors had a 5-year recurrence free survival rate of 65%. These patients would be suitable for studies of postoperative adjuvant therapy to improve outcome.     

Does histology influence prognosis in patients with early-stage cervical carcinoma?

BACKGROUND: The objective of this study was to examine the influence of histology on the outcome of patients with surgically treated, Stage IA-IB carcinoma of the uterine cervix. METHODS: All patient information was collected prospectively and was extracted subsequently from the University of Toronto cervical carcinoma surgery data base. Selection criteria for surgery were based on tumor size and were independent of histology. Patients with adenocarcinoma were separated into two groups: those with mucinous/endometrioid adenocarcinoma (M/E AC) and those with adenosquamous/clear cell adenocarcinoma (AS/CC AC). Statistical analysis used Wilcoxon rank tests, Mantel-Hanzel tests, chi-square tests, and Cox regression analyses. RESULTS: Between July 1984 and January 2000, 880 patients with Stage IA-IB cervical carcinoma underwent radical surgery, including pelvic lymphadenectomy, as the primary treatment. Two hundred fifty-five patients had M/E AC (29%), 81 patients had AS/CC AC (9%), and 544 patients had squamous cell carcinoma (SCC; 62%). Compared with patients who had SCC, patients with M/E AC had significantly more favorable prognostic characteristics: age (median, 39 years vs. 41 years; P < 0.03), depth of invasion (3.7 mm vs. 5.5 mm; P < 0.001), vascular space involvement (24% vs. 57%; P < 0.0001), Grade 2-3 tumor (40% vs. 78%; P < 0.0001), and pelvic lymph node metastases (4% vs. 8%; P < 0.04), respectively. Characteristics among patients with AS/CC AC tended have values similar to the median values for patients with SCC (or intermediate between the values for patients with M/E AC and the values for patients with SCC): age (38 years), depth of invasion (6 mm), vascular space involvement (40%), Grades 2-3 (70%), and pelvic lymph node metastases (6%). The 2-year and 5-year recurrence free survival rate was similar between patients with M/E AC and patients with SCC (95% vs. 94% and 90% vs. 90%, respectively); however, both were significantly superior to the rates for patients with AS/CC AC (2-year recurrence free survival rate: 86%, P < 0.03; 5-year recurrence free survival rate: 81%, P % 0.03). There were no differences in the pattern of first recurrence by histology. CONCLUSIONS: Patients with surgically treated Stage IA-IB cervical carcinoma with M/E AC and SCC histology have a similar prognosis. For patients with disease with AS/CC AC histology, the current results and the literature indicate that patients with uncommon histologies have an inferior recurrence free survival rate. Although the optimal therapy for these patients remains undefined, there is no obvious rationale for altering the treatment strategies from those currently employed for patients with M/E AC and SCC.     

Surface fractal computation and its application to immunofluorescent histochemical studies of calpain and calpastatin in PC12 cells

The purpose of this report is to present a method which can be used to parameterize patterns of immunofluorescent staining in cultured neural cells. The algorithm is based on the observation that the variance in pixel intensity of the image is a power function of the magnitude of the area in immunofluorescently stained PC12 cells. This property is used to derive the fractal dimension (D) of the region of interest (ROI), and corresponds to the complexity of the pixel intensity associated with the ROI, which is analogous to a fractal surface. We show that the measure is useful in characterizing immunofluorescent staining patterns, and apply this measure to study the effects of ethanol exposure on mu-calpain and calpastatin-associated immunoreactivity. Exposure of PC12 cells to ethanol (80 mM)x48 h resulted in alterations in immunofluorescent signal (Control vs ethanol) associated with actin, calpastatin and mu-calpain: 2289+/-166 vs 1709+/-69, P<0.01; 1681+/-38 vs 2224+/-95, P<0.001; 1823+/-39 vs 2841+/-68, P<0.0001 respectively, magnitudes being pixel intensity units on a scale of 0-4095. D-values for the three proteins in the same order were: 2.32+/-0.01 vs 2.31+/-0.03, NS; 2.31+/-0.01 vs 2.32+/-0.01, NS; 2.16+/-0.03 vs 2. 24+/-0.02, P<0.01, with a possible D-value range of 2-3.     

Differential effects of MK801 and lorazepam on heart rate variability in adolescent rhesus monkeys (macaca mulatta)

Previous research shows that ketamine significantly alters cardiac signal regulation in rhesus monkeys, however relatively little is known about the mechanism for this effect. In the study reported here the relative contributions of NMDA receptor activation on cardiac signal dynamics were determined by administering a specific NMDA antagonist, MK801, to rhesus monkeys. The general effects of sedation were assessed by measuring cardiac response to lorazepam, a sedative drug without direct NMDA receptor activity. Electrocardiographic signal dynamics were examined before and after I.V. administration of either MK801 (0.16 mg/kg) or lorazepam (0.48 mg/kg). Inter-beat interval time series data were analyzed in the frequency domain after Fourier transform, and a nonlinear measure of autocorrelation, the Hurst exponent (H), was derived. After MK801 administration, log [HF /Total power] increased post-infusion (M = 1.11, SD = 0.45) compared with pre-infusion values [M = -0.19, SD = 0.32, F(1,4) = 19.49, P = 0.01] while H decreased, mean pre versus post 0.52+/-S.D. 0.10 versus 0.01+/- 0.05, P = 0.0002. Lorazepam administration did not significantly alter heart rate variability measures obtained in the frequency or nonlinear domains. To our knowledge, this is the first study that has defined the effects of peripherally administered MK801 on cardiovascular dynamics in primates and establishes that peripheral administration of NMDA antagonists result in large increases the high-frequency components of cardiac rhythm and increased heart rate variability compatible with MK801-associated increases in parasympathetic outflow.     

Physicians' perspective on quality of life: An exploratory study of oncologists

There is an implicit assumption that physicians incorporate quality of life (QOL) information in clinical decision-making. However, very limited data exists on how physicians view QOL information and how they actually use it. To explore this issue, an in-depth study was conducted using a semistructured interview guide, with 60 oncologists in Canada and the USA. While the majority of respondents perceived QOL as important they reported a tendency to use it informally and not in all situations. Key findings include the belief expressed by 88% of respondents that the term QOL could be defined, although they differed in their definitions. Although 85% stated that QOL can be formally measured, only a third perceived that the current instruments provide valid and reliable data. Respondents noted a number of significant benefits and drawbacks of using QOL data in their clinical practice that had not been previously noted in the literature. For example, its use as an endpoint in clinical trials was generally perceived to enhance both physician and patient participation. A drawback noted was that including QOL might adversely affect the decision-making process. These findings have been used to develop a self-administered questionnaire (MD-QOL) which will test the generalizability of these findings.     

Adenocarcinoma in a cecal neovagina--complication of irradiation: report of a case and review of literature

A 42-year-old woman is presented with her fifth primary pelvic carcinoma, occurring in an irradiated cecal neovagina. Previously reported neovaginal carcinomas are reviewed. The possible etiologies are examined. This is the first case of radiation-induced carcinoma arising in a cecal neovagina. Long-term follow-up is important in all patients with neovaginas.