Circulating microRNAs predict biochemical recurrence in prostate cancer patients.

BACKGROUND: Circulating microRNAs (miRNAs) are emerging as promising biomarkers for prostate cancer. Here, we investigated the potential of these molecules to assist in prognosis and treatment decision-making. METHODS: MicroRNAs in the serum of patients who had experienced rapid biochemical recurrence (BCR) (n=8) or no recurrence (n=8) following radical prostatectomy (RP) were profiled using high-throughput qRT-PCR. Recurrence-associated miRNAs were subsequently quantitated by qRT-PCR in a validation cohort comprised of 70 patients with Gleason 7 cancers treated by RP, 31 of whom had undergone disease progression following surgery. The expression of recurrence-associated miRNAs was also examined in tumour tissue cohorts. RESULTS: Three miRNAs - miR-141, miR-146b-3p and miR-194 - were elevated in patients who subsequently experienced BCR in the screening study. MiR-146b-3p and miR-194 were also associated with disease progression in the validation cohort, as determined by log-rank tests and Cox proportional hazards regression. Multivariate analysis revealed that miR-146b-3p possessed prognostic information beyond standard clinicopathological parameters. Analysis of tissue cohorts revealed that miR-194 was robustly expressed in the prostate, elevated in metastases, and its expression in primary tumours was associated with a poor prognosis. CONCLUSION: Our study suggests that circulating miRNAs, measured at the time of RP, could be combined with current prognostic tools to predict future disease progression in men with intermediate risk prostate cancers.

Migrating birds respond to Project Seafarer's electromagnetic field.

Radar tracking of individual migrating birds flying over a large alternating-current antenna system showed that the birds turned or changed altitude more frequently when the antenna system was operating than when it was not. These results suggest that birds sense low-intensity alternating-current electromagnetic fields during nocturnal migratory flight.

Elevated levels of peritumoral chondroitin sulfate are predictive of poor prognosis in patients treated by radical prostatectomy for early-stage prostate cancer.

The disease course of localized prostate cancer is highly variable, and patients potentially curable by aggressive management are not readily identified by current clinical practice. Chondroitin sulfate (CS) glycosaminoglycan is a candidate biomarker as elevated levels of CS in peritumoral stroma of prostate cancer have been associated with prostate-specific antigen (PSA) failure. Immunoreactive CS was measured using image analysis of archived radical prostatectomy tissues, obtained from 157 men with a median of 47 months (range, 16-111 months) clinical follow-up. CS level, Gleason score, and preoperative serum PSA levels were independent predictors of PSA failure by Cox's multivariate analysis. Patients with low CS levels had significantly fewer PSA failures after radical prostatectomy than patients with high levels of CS (Kaplan-Meier plot; 32% PSA failures at 5 years for CS mean integrated absorbance cut point < 7.0 versus 50% for CS > or = 7.0, P = 0.0001). In the subgroup of patients with preoperative serum PSA levels < 10 ng/ml, CS was particularly useful in discriminating retrospectively those patients most suited for surgery (Kaplan-Meier plot; 14% PSA failures at 5 years for CS mean integrated absorbance cut point < 7.0 versus 47% for CS > or = 7.0, P = 0.0001). We conclude that measurements of CS level can assist in predicting patient outcome after surgery. Additionally, our data suggest that the combination of CS and PSA measurements may improve outcome prediction for patients with intermediate Gleason scores.

Plasminogen activator inhibitor and the risk of cardiovascular disease: The Framingham Heart Study.

INTRODUCTION: Although plasminogen activator inhibitor (PAI-1) plays a key regulatory role in fibrinolysis, it has not been clearly shown to independently predict cardiovascular disease (CVD) among individuals without prior CVD. We investigated, in the Framingham Heart Study offspring cohort, whether PAI-1 predicted CVD risk among individuals without prior CVD. METHODS: Plasma PAI-1 antigen and tissue plasminogen activator (TPA) antigen were measured in 3203 subjects without prior CVD between 1991 and 1995; average follow-up of 10 years. PAI-1 was remeasured 4 years after baseline, to determine the effect of serial change on risk. RESULTS: PAI-1 levels (mean ± SD) were 29.1 ng/ml (19.2) versus 22.1 (16.5) for those and without incident CVD; p<0.001, and TPA levels were 12.0 ng/ml (5.7) versus 9.0 (4.7); p<0.001. PAI-1 and TPA antigen levels had a strong unadjusted linear relation with incident CVD (p<0.001). After adjustment for conventional risk factors, the hazard ratios (HRs) for higher quartiles of PAI-1, compared with the lowest, were 1.9, 1.9, 2.6 (linear trend p=0.006), and 1.6, 1.6, 2.9 (p<0.001) for TPA antigen. The adjusted HRs for increasing quartiles of serial change in PAI-1 at 4 years, compared with the lowest, were 0.9, 0.8, 1.3 (p=0.050). C statistic assessment showed that adding PAI-1 or TPA to conventional risk factors resulted in small increases in discrimination and modest reclassification of risk, which was statistically significant for TPA (net reclassification 6.8%, p=0.037) but not PAI-1 (4.8%, p=0.113). CONCLUSION: PAI-1 and TPA antigen levels are predictive of CVD events after accounting for established risk factors. A serial increase in PAI-1 is associated with a further increase in risk. These findings support the importance of fibrinolytic potential in CVD.

Studies on the luminescent response of the Ca2+-activated photoprotein, obelin.

1. The kinetics and stoicheiometry of the Ca2+-activated luminescent reaction of the photoprotein obelin were studied at different temperatures and in the presence of various substances, including the physiologically occurring cations K+, Na+, Ca+, Mg2+ and H+. 2. The results suggest Ca2+-independent rates of rise and fall in obelin luminescence following sudden changes in [Ca2+] and indicate that changes in [Ca2+] over the range 1 x 10(-6) - 3 x 10(-4) M are followed significantly faster by the obelin response (approx. 3 ms delay at 20 degrees C) than by the aequorin response (approx. 10 ms delay at 20 degrees C). 3. Obelin was found to emit low-intensity light (less than 10(-6) of the maximum Ca2+-activated response), which was independent of Ca2+ at concentrations below about 10(-7) M. The level of this Ca2+-independent light emission is sensitive to temperature and the ionic composition of the solution. 4. The log-log plot of light intensity against ionized Ca indicates a maximum slope of 2.5, suggesting the involvement of three Ca ions in the luminescent reaction. 5. Increase in the concentration of K+, Na+, Mg2+ and H+ generally shift the Ca2+ activation curve for obelin toward higher Ca2+ concentrations. These cations can also affect the maximum rate of obelin utilization at more extreme concentrations. 6. The maximal rate of obelin utilization was also affected to varying degrees by the presence of uncharged substances such as glucose, sucrose and polyvinylpyrrolidone. However, neither the sensitivity of obelin to Ca2+ nor the quantum yield were modified by the substances. 7. Caffeine (less than 20 mM), procaine (less than 20 mM) and sodium dantrolene (saturated solution), substances known to modify cellular Ca2+ movements, had little effect on the Ca2+-induced luminescent reaction. The general anaesthetics chlorpromazine and halothane appeared to lower greatly the quantum yield without, however, modifying the maximum rate of obelin utilization. 8. A scheme of reaction for obelin activation by Ca2+ is presented which adequately explains the experimental observations and allows one to make accurate predictions regarding the relative obelin response under a variety of ionic conditions at room temperature.

Genetic and environmental contributions to platelet aggregation: the Framingham heart study.

BACKGROUND: Platelet aggregation plays an important role in arterial thrombosis in coronary heart disease, stroke, and peripheral arterial disease. However, the contribution of genetic versus environmental influences on interindividual variation in platelet aggregability is poorly characterized. METHODS AND RESULTS: We studied the heritability of platelet aggregation responses in 2413 participants in the Framingham Heart Study. The threshold concentrations of epinephrine and ADP required to produce biphasic platelet aggregation and collagen lag time were determined. Mixed-model linear regression was used to calculate correlation coefficients within sibships and within spouse pairs. Variance and covariance component methods were used to estimate the proportion of platelet aggregation attributable to measured covariates versus additive genetic effects. After accounting for environmental covariates, the adjusted sibling correlations for epinephrine, ADP, and collagen lag time were 0.24, 0.22, and 0.31, respectively (P=0.0001 for each). In contrast, adjusted correlations for spouse-pairs were -0.01, 0.05, and -0.02, respectively (all P>0.30). The estimated heritabilities were 0.48, 0.44, and 0.62, respectively. Measured covariates accounted for only 4% to 7% of the overall variance in platelet aggregation, and heritable factors accounted for 20% to 30%. The platelet glycoprotein IIIa Pl(A2) polymorphism and the fibrinogen Hind III beta-148 polymorphism contributed <1% to the overall variance. CONCLUSIONS: In our large, population-based sample, heritable factors play a major role in determining platelet aggregation, and measured covariates play a lesser role. Future studies are warranted to identify the key genetic variants that regulate platelet function and to lay the groundwork for rational pharmacogenetic approaches.

Association of blood pressure with fibrinolytic potential in the Framingham offspring population.

BACKGROUND: Hypertension is an established risk factor for acute coronary events. Because fibrinolytic and hemostatic factors are also associated with cardiovascular disease, we examined the relations of systolic and diastolic blood pressures (SBP and DBP) to levels of plasminogen activator inhibitor antigen, tissue plasminogen activator antigen, fibrinogen, factor VII, von Willebrand factor, fibrinogen, and plasma viscosity in subjects of the Framingham Offspring Study. METHODS AND RESULTS: We studied 1193 men and 1459 women after the exclusion of subjects with known cardiovascular disease and those receiving anticoagulant or antihypertensive therapy. Linear regression models were used to evaluate SBP and DBP as predictors of fibrinolytic and hemostatic factor levels in separate sex models, with adjustment for age, body mass index, smoking, diabetes, total cholesterol, HDL, triglycerides, alcohol intake, and estrogen use (in women). In both sexes, levels of plasminogen activator inhibitor and tissue plasminogen activator antigen were positively related to SBP and DBP (P<0.001). Plasma viscosity was positively related to SBP (P=0.008) and DBP (P=0.001) in women only. There was no association between SBP or DBP and fibrinogen, factor VII, or von Willebrand factor in either sex. CONCLUSIONS: These data suggest that impaired fibrinolysis may play an important role in the pathogenesis of cardiovascular disease in hypertensive patients.

Association of fibrinogen with cardiovascular risk factors and cardiovascular disease in the Framingham Offspring Population.

BACKGROUND: Fibrinogen has been identified as an independent risk factor for cardiovascular disease and associated with traditional cardiovascular risk factors. Also, the role of elevated fibrinogen in thrombosis suggests that it may be on the causal pathway for certain risk factors to exert their effect. These associations remain incompletely characterized. Moreover, the optimal fibrinogen assay for risk stratification is uncertain. METHODS AND RESULTS: In 2632 subjects from cycle 5 of the Framingham Offspring Population, fibrinogen levels were determined with a newly developed immunoprecipitation test (American Biogenetic Sciences) and the functional Clauss method. With the immunoprecipitation method, there were significant linear trends across fibrinogen tertiles (P:<0.001) for age, body mass index, smoking, diabetes mellitus, total cholesterol, HDL cholesterol, and triglycerides in men and women. The Clauss method had significant results (P:<0.030), except for triglycerides in men. Fibrinogen levels were higher for those with compared with those without cardiovascular disease. After covariate adjustment, fibrinogen remained significantly higher in those with cardiovascular disease with the use of the immunoprecipitation test (P:=0.035 and P:=0.018 for men and women, respectively) but not with the Clauss method. CONCLUSIONS: Fibrinogen was associated with traditional cardiovascular risk factors. Elevation of fibrinogen may provide a mechanism for risk factors to exert their effect. Also, fibrinogen levels were higher among subjects with cardiovascular disease compared with those without disease. The immunoprecipitation test showed a stronger association with cardiovascular disease than the Clauss method, suggesting that it may be a useful screening tool to identify individuals at increased thrombotic risk.

Platelet glycoprotein IIIa Pl(a) polymorphism, fibrinogen, and platelet aggregability: The Framingham Heart Study.

BACKGROUND: Recent data suggest that the Pl(A2) allele of the platelet glycoprotein IIIa receptor may be a genetic risk factor for cardiovascular disease. We previously reported that the Pl(A2) allele was associated with increased platelet aggregability, as indicated by lower epinephrine threshold concentrations. Paradoxically, however, it has been reported that Pl(A2)-positive platelets have reduced fibrinogen binding. Because fibrinogen mediates platelet aggregability, we hypothesized that plasma fibrinogen levels may interact with Pl(A) genotype in modulating platelet aggregability. Methods and Results-- Glycoprotein IIIa Pl(A) genotype, fibrinogen level, and platelet aggregability were ascertained in 1340 subjects enrolled into the Framingham Offspring Study. Platelet aggregability was evaluated by the Born method. Higher fibrinogen levels were associated with increased epinephrine-induced aggregation (P=0.002) and a trend for ADP-induced aggregation (P=0.07). The fibrinogen effect was genotype specific, however, in that the increase in platelet aggregability with higher fibrinogen was present for the Pl(A1/A1) genotype (P=0.0005 and P=0.03 for epinephrine- and ADP-induced aggregation, respectively) but not for the Pl(A2)-positive genotype (P>0.90). CONCLUSION: Higher fibrinogen levels were associated with increased platelet aggregability. However, the association between fibrinogen and platelet aggregability was genotype specific. This interaction may be responsible for the conflicting findings regarding Pl(A) genotype and platelet aggregability. Further study of this gene-environment interaction may provide insight into cardiovascular disease risk.

Alcohol consumption and hemostatic factors: analysis of the Framingham Offspring cohort.

BACKGROUND: Moderate alcohol consumers have lower rates of cardiovascular disease than abstainers. One proposed mechanism is a beneficial effect on hemostatic parameters, but previous studies have provided conflicting results. METHODS AND RESULTS: We measured levels of fibrinogen, plasma viscosity, von Willebrand factor, factor VII, plasminogen activator inhibitor antigen-1, and tissue plasminogen activator antigen in a cross-sectional analysis of 3223 adults free of cardiovascular disease enrolled in the Framingham Offspring Study. We assessed their alcohol consumption with a standardized questionnaire. Light-to-moderate alcohol consumption was associated with lower levels of fibrinogen, plasma viscosity, von Willebrand factor, and factor VII. This association was most pronounced for consumers of 3 to 7 drinks weekly for viscosity and 7 to 21 drinks weekly for the other hemostatic measures. Alcohol intake of 7 to 21 drinks weekly or more was associated with impaired fibrinolytic potential, reflected by higher levels of plasminogen activator inhibitor antigen-1 and tissue plasminogen activator antigen. Wine drinkers had lower plasminogen activator inhibitor antigen-1 levels than other drinkers, particularly at 3 to 21 drinks weekly, but beverage type did not otherwise consistently affect the results. CONCLUSIONS: Light-to-moderate alcohol consumption is associated with lower levels of coagulatory factors, but higher intake is associated with impaired fibrinolytic potential. These findings are consistent with the hypothesis that a balance between hemostatic and fibrinolytic activity may contribute to the complex relation of alcohol use with coronary heart disease.

Sexual relationships between physicians and patients.

In the face of evidence suggesting that there is a substantial incidence of sexual contact between physicians of all specialties and their patients, the medical profession and the courts have not yet reached a consensus regarding appropriate responses. Some commentators, including the American Medical Association, have urged bans on sexual contact during treatment and extensive restriction of posttreatment sexual relationships. Others favor looser restrictions, particularly after termination of the physician-patient relationship. These differences in approach stem from the varying importance given the two conflicting values involved: (1) protecting patients from being harmed by unfair manipulation by physicians and (2) insulating choices about intimate relationships from intrusion by society. We propose a model for balancing these interests that would bar sexual contact during the physician-patient relationship and for a fixed period after termination; thereafter, in most cases, sexual relationships would not be proscribed. A waiting-period approach of this sort is likely to diminish most of the harms that might result from physician-patient sexual contact and may constitute a template for the resolution of similar issues elsewhere in society.

Dark green islands in plant virus infection are the result of posttranscriptional gene silencing.

Dark green islands (DGIs) are a common symptom of plants systemically infected with a mosaic virus. DGIs are clusters of green leaf cells that are free of virus but surrounded by yellow, virus-infected tissue. We report here on two lines of evidence showing that DGIs are caused by posttranscriptional gene silencing (PTGS). First, transcripts of a transgene derived from the coat protein of Tamarillo mosaic potyvirus (TaMV) were reduced in DGIs relative to adjacent yellow tissues when the plants were infected with TaMV. Second, nontransgenic plants coinfected with TaMV and a heterologous virus vector carrying TaMV sequences showed reduced titers of the vector in DGIs compared with surrounding tissues. DGIs also were compared with recovered tissue at the top of transgenic plants because recovery has been shown previously to involve PTGS. Cytological analysis of the cells at the junction between recovered and infected tissue was undertaken. The interface between recovered and infected cells had very similar features to that surrounding DGIs. We conclude that DGIs and recovery are related phenomena, differing in their ability to amplify or transport the silencing signal.

Cell-to-cell movement of potexviruses: evidence for a ribonucleoprotein complex involving the coat protein and first triple gene block protein.

The triple gene block proteins (TGBp1-3) and coat protein (CP) of potexviruses are required for cell-to-cell movement. Separate models have been proposed for intercellular movement of two of these viruses, transport of intact virions, or a ribonucleoprotein complex (RNP) comprising genomic RNA, TGBp1, and the CP. At issue therefore, is the form(s) in which RNA transport occurs and the roles of TGBp1-3 and the CP in movement. Evidence is presented that, based on microprojectile bombardment studies, TGBp1 and the CP, but not TGBp2 or TGBp3, are co-translocated between cells with viral RNA. In addition, cell-to-cell movement and encapsidation functions of the CP were shown to be separable, and the rate-limiting factor of potexvirus movement was shown not to be virion accumulation, but rather, the presence of TGBp1-3 and the CP in the infected cell. These findings are consistent with a common mode of transport for potexviruses, involving a non-virion RNP, and show that TGBp1 is the movement protein, whereas TGBp2 and TGBp3 are either involved in intracellular transport or interact with the cellular machinery/docking sites at the plasmodesmata.

Hyperhomocysteinemia and traditional cardiovascular disease risk factors in end-stage renal disease patients on dialysis: a case-control study.

Hyperhomocysteinemia occurs frequently in end-stage renal disease (ESRD), but its prevalence in comparison with traditional cardiovascular disease (CVD) risk factors is unknown. Fasting total plasma homocysteine, potential determinants of plasma homocysteine (i.e., plasma B-vitamins and serine), total and HDL cholesterol, glucose, and creatinine, were determined in 24 ESRD patients on dialysis, and 24 age, gender, and race matched Framingham Offspring Study controls with normal renal function. Presence of clinical CVD and CVD risk factors was established by standardized methods. Mean plasma homocysteine was markedly higher in the ESRD patients versus controls (22.7 vs. 9.5 mumol/l). ESRD patients were 33 times more likely than controls to have hyperhomocysteinemia (> 15.8 mumol/l) (95% confidence interval, 5.7-189.6). Hyperhomocysteinemia persisted in the ESRD patients despite normal to supernormal B-vitamin status. Plasma serine levels below the tenth percentile of the control distribution were found in 75% of the ESRD patients. Oral serine supplementation caused a 37% increase in mean plasma serine, but had no effect on plasma homocysteine in four ESRD patients with supernormal plasma folate, low plasma serine, and hyperhomocysteinemia. Given its unusually high prevalence, improved management of hyperhomocysteinemia might reduce CVD sequelae in ESRD.

Hyperhomocysteinemia, hyperfibrinogenemia, and lipoprotein (a) excess in maintenance dialysis patients: a matched case-control study.

Maintenance dialysis patients experience an exceedingly high incidence of arteriosclerotic cardiovascular disease (CVD) events that are poorly predicted by traditional CVD risk factor indices. We evaluated the prevalence of three non-traditional CVD risk factors, i.e. hyperhomocysteinemia, hyperfibrinogenemia, and lipoprotein (a) Lp(a)) excess, and combined hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess, in maintenance dialysis patients. Fasting total plasma homocysteine (Hcy), fibrinogen, Lp(a), glucose, and total and HDL cholesterol levels, and traditional CVD risk factor (i.e. glucose tolerance, smoking, hypertension, dyslipidemia) prevalences were assessed in 71 dialysis patients and 71 age, sex, and race matched Framingham Study controls free of clinical renal disease, with normal serum creatinine (< or = 1.5 mg/dl). Mean plasma Hcy 23.7 vs. 9.9 microM, P = 0.0001), fibrinogen (457 vs. 309 mg/dl, P = 0.0001), and Lp(a) (30 vs. 17 mg/dl, P = 0.0070) levels were substantially increased in the dialysis patients. Matched odds ratios (with 95% confidence intervals), dialysis patients/controls, for hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess, alone or combined, were markedly greater in the dialysis patients, with no evidence of confounding by the traditional CVD risk factors: hyperhomocysteinemia, 105.0 (29.9-368.9); hyperfibrinogenemia, 16.6 (6.6-42.0); Lp(a) excess, 3.5 (1.5-8.4); all three combined 35.0 (5.7-199.8). Given in vitro evidence that Hcy, Lp(a), and fibrinogen interact to promote atherothrombosis, combined hyperhomocysteinemia, hyperfibrinogenemia, and Lp(a) excess may contribute to the high incidence of vascular disease sequelae experienced by dialysis patients, which is inadequately explained by traditional CVD risk factors. Controlled, prospective studies of well-characterized maintenance dialysis cohorts are urgently required to substantiate this hypothesis.

Folate status is the major determinant of fasting total plasma homocysteine levels in maintenance dialysis patients.

Limited data are available on the determinants of homocysteinemia or the association between plasma homocysteine (Hcy) levels and prevalent cardiovascular disease (CVD) in maintenance dialysis patients. We assessed etiology of renal failure, residual renal function and dialysis adequacy-related variables, and vitamin status, as determinants of fasting total plasma homocysteine (Hcy) in 75 maintenance dialysis patients. We also assessed the potential interactive effect on plasma Hcy of folate status and a common mutation (ala to val; homozygous val-val frequency approximately 10%) in methylenetetrahydrofolate reductase (MTHFR), a folate-dependent enzyme crucial for the remethylation of homocysteine (Hcy) to methionine. Lastly, we evaluated whether the Hcy levels differed amongst these patients in the presence or absence of prevalent CVD, after adjustment for the traditional CVD risk factors. Fasting total plasma Hcy, folate, pyridoxal 5'-phosphate (PLP; active B6), B12, creatinine, glucose, total and HDL cholesterol levels, and presence of the ala to val MTHFR mutation were determined, and clinical CVD and CVD risk factor prevalence were ascertained. General linear modelling/analysis of covariance revealed: (1) folate status and serum creatinine were the only significant independent predictors of fasting Hcy; (2) there was a significant interaction between presence of the val mutation and folate status, i.e., among patients with plasma folate below the median (< 29.2 ng/ml), geometric mean Hcy levels were 33% greater (29.0 vs. 21.8 microM, P = 0.012) in the pooled homozygotes (val-val) and heterozygotes (ala-val) for the ala to val mutation, vs. normals (ala-ala); (3) there was no association between prevalent CVD and plasma Hcy. Given potentially intractable survivorship effects, prospective cohort studies will be required to clarify the relationship between plasma Hcy or any putative CVD risk factor, and incident CVD in dialysis patients. If a positive association between plasma Hcy and incident CVD can be established in maintenance dialysis patients, the current data provide a rationale for additional folic acid supplementation in this patient population.

Pregnancies after ultrasound-guided fallopian insemination with cryostored donor semen.

Twenty-nine patients, previously treated unsuccessfully with a median 9.5 cycles of conventional intracervical donor insemination, were offered fallopian catheterization on the side of the dominant follicle and direct insemination at the presumed site of fertilization, the ampullary-isthmic junction. Forty-five of 50 cycles were associated with successful tubal catheterization and 6 of these cycles were conceptional. Five viable intrauterine pregnancies resulted. We conclude: (1) that direct sperm transfer to the fallopian tubes is possible without the need for anesthesia or operation; and (2) that at the time of ovulation, the fallopian tube isthmus can be catheterized without later interfering with ovum or embryo transport to the uterus. Optimum timing for fallopian catheterization in relation to ovulation and the risk of side effects both remain to be established.

The influence of Org 10172, an antithrombotic heparinoid, on urinary blood loss after transurethral prostatectomy.

We have measured the effects of Org 10172 (a mixture of naturally occurring glycosaminoglycans derived from hog intestinal mucosa) on blood loss after transurethral prostatectomy (TURP), using doses which are likely to prevent postoperative venous thrombosis (VT). 48 patients entered a double-blind randomised pilot study: 18 were given subcutaneous (sc) injections of a placebo and 30 received sc Org 10172 (750 anti-Xa units/day, 500 units twice daily (bid), or 750 units bid, starting just before TURP and continued until discharge; 10 patients per group). No Org 10172 regimen increased peroperative blood loss but all caused a similar trend towards increased urinary bleeding after surgery. Since there was no apparent dose effect gradient, it was decided to pool the data from all three dosing blocks: this analysis showed that Org 10172 increased geometric mean blood loss during the first 2 days after surgery from 10.4 gm hemoglobin (Hgb; range = 3.2-71) to 20.5 gm Hgb (range = 1.9-147) (p = .005), an effect which retained its significance after allowing for two other major determinants of postoperative bleeding, the weight of prostate resected and the length of surgery, and also when pooling was restricted to the twice daily Org 10172 injection groups and their corresponding controls. Bleeding was not severe, but our results indicate a need for caution when considering the use of Org 10172 in this setting.

Improved accuracy of the occlusion technique for assessing total respiratory compliance in infants.

The occlusion technique to measure total respiratory system compliance (Cocc) was used in 28 sedated infants with a variety of cardiopulmonary diseases and 14 anaesthetised infants during the first 2 years of life. In this report, we describe some of the potential problems in the technique and how to avoid them. Invalidation of the occlusion technique because of consistent failure to relax during brief airway occlusions occurred in only four of 42 infants despite the fact that only four infants were studied during the first month of life and 17 were between 12 and 26 months old. The technique was invalidated in two intubated infants because of persistent leaks around the endotracheal tube. In the remaining 36 infants, data sometimes had to be excluded as a result of instability and end-expiratory volume, intermittent leaks, or failure to relax during occlusions performed at low lung volumes or during inspiration. However, by performing 15-25 occlusions per infant, it was possible to obtain sufficient reliable data for accurate analysis of Cocc in all these infants. Providing that the potential errors and limitations of the occlusion technique are recognized, it appears to be applicable to a wide range of healthy and sick infants.

Nellcor Stat Cap differentiates oesophageal from tracheal intubation.

A trial of the Nellcor Stat Cap, which detects exhaled carbon dioxide, as an aid to determining whether endotracheal tubes are placed in the oesophagus or the trachea, was carried out in the neonatal unit of this hospital. Twenty five neonates, with a mean (range) gestational age of 33 (24-42) weeks and a mean (range) birthweight of 2.17 (0.54-4.1) kg were studied over two months. These babies underwent a total of 58 intubations and 20 suspected self-extubations. The Nellcor Stat Cap was easy to use. It confirmed clinical findings on 20/20 occasions when the endotracheal tube was in the oesophagus and on 57/58 (98%) occasions when it was in the trachea. On 14/78 (19%) occasions the machine provided helpful additional information in reaching a decision on the adequacy of tube placement. Failure to detect rapidly accidental oesophageal intubation or unintentional tracheal extubation can result in rapid deterioration of the condition of ventilated newborns. The machine is a valuable aid to intubation and rapid diagnosis of self-extubation.