Fetal intervention for severe lower urinary tract obstruction: a multicenter case-control study comparing fetal cystoscopy with vesicoamniotic shunting.

OBJECTIVE: To evaluate the efficacy of fetal intervention using fetal cystoscopy or vesicoamniotic shunting in the treatment of severe lower urinary obstruction (LUTO). METHODS: A cohort of 111 fetuses with severe LUTO attending two centers between January 1990 and August 2013 were included retrospectively. Fetuses were categorized into three groups based on the method of intervention: (1) fetal cystoscopy, (2) vesicoamniotic shunting or (3) no intervention. Multivariate analyses were performed to determine the probability of survival and normal renal function until 6 months of age by comparing fetal cystoscopy and vesicoamniotic shunting to no fetal intervention. RESULTS: Of the 111 fetuses with severe LUTO that were included in the analysis, fetal cystoscopy was performed in 34, vesicoamniotic shunting was performed in 16 and there was no fetal intervention in 61. Gestational age at diagnosis, method of fetal intervention and cause of bladder obstruction were associated with prognosis. In multivariate analysis and after adjustment for potential confounders (considering all causes of LUTO) the overall probability of survival was significantly higher with fetal cystoscopy and vesicoamniotic shunting when compared to no intervention (adjusted relative risk (ARR), 1.86 (95% CI, 1.01-3.42; P = 0.048) and ARR, 1.73 (95% CI, 1.01-3.08; P = 0.04) respectively). A clear trend for normal renal function was present in the fetal cystoscopy group (ARR, 1.73 (95% CI, 0.97-3.08; P = 0.06)) but was not observed in the vesicoamniotic shunt group (ARR, 1.16 (95% CI, 0.86-1.55; P = 0.33)). In cases in which there was a postnatal diagnosis of posterior urethral valves, fetal cystoscopy was effective in improving both the 6-month survival rate and renal function (ARR, 4.10 (95% CI, 1.75-9.62; P < 0.01) and 2.66 (95% CI, 1.25-5.70; P = 0.01) respectively) while vesicoamniotic shunting was associated only with an improvement in the 6-month survival rate (ARR, 3.76 (95% CI, 1.42-9.97; P < 0.01)) with no effect on renal function (ARR, 1.03 (95% CI, 0.49-2.17, P = 0.93)). CONCLUSION: Fetal cystoscopy and vesicoamniotic shunting improve the 6-month survival rate in cases of severe LUTO. However, only fetal cystoscopy may prevent impairment of renal function in fetuses with posterior urethral valves. Our data support the idea of performing a subsequent randomized controlled trial to compare the effectiveness of fetal cystoscopy vs vesicoamniotic shunting for severe fetal LUTO.

Baculoviruses in populations of western spruce budworm.

Population studies of western spruce budworm, Choristoneura occidentalis, revealed that a baculovirus, ChocNPV, was widespread in outbreak populations over a broad geographical area of British Columbia, Canada although the rate of mortality was usually low (<5%). Elevated levels of ChocNPV-related mortality (≈20%) were found when western spruce budworm populations reached high densities (≈300 larvae per kg of Douglas-fir foliage) and contributed to declines in population densities in these areas. A subsample from budworm collections examined using a multiplex-PCR assay showed ChocNPV was the most prevalent virus but also often occurred in combination with a granulovirus, ChocGV and a cypovirus, CoCPV.

Prognostic Significance of the Microenvironment in Human Papillomavirus Oropharyngeal Carcinoma: A Systematic Review.

OBJECTIVE: The immune microenvironment of HPV-associated (HPV+) oropharyngeal squamous cell carcinomas (OPSCCs) (HPV+OPSCCs) differs from that of HPV-independent oropharyngeal cancers (HPV-independent OPSCCs). The literature on the subject is very abundant, demanding an organized synthesis of this wealth of information to evaluate the hypothesis associating the favorable prognosis of HPV+OPSCC patients with a different immune microenvironment. A systematic review of the literature was conducted regarding the microenvironment of HPV+OPSCCs. DATA SOURCE: MEDLINE/PubMed, Embase, and Cochrane Library databases. REVIEW METHODS: A literature search was performed following PRISMA guidelines (Moher D. PLoS Med. 2009). The PEO (Population, Exposure, and Outcome) framework is detailed as follows: P: patients with oropharyngeal squamous cell carcinomas, E: human papillomavirus (HPV), and O: histological and immunological composition of the tumoral microenvironment (TME). No meta-analysis was performed. RESULTS: From 1,202 studies that were screened, 58 studies were included (n = 6,474 patients; n = 3,581 (55%) HPV+OPSCCs and n = 2,861(45%) HPV-independent OPSCCs). The presence of tumor-infiltrating lymphocytes (TIL), CD3+ in 1,733 patients, CD4+ in 520 patients, and CD8+ (cytotoxic T lymphocytes (CTL)) in 3,104 patients, and high levels of PD-L1 expression in 1,222 patients is strongly correlated with an improved clinical outcome in HPV+OPSCCs. CONCLUSION: This systematic review provides the most comprehensive information on the immune microenvironment of HPV+OPSCCs to date. Tumor-infiltrating lymphocytes and PD-L1 expression are associated with a favorable prognosis. B, CD8+ and resident memory cells densities are higher in HPV+OPSCCs. The importance of myeloid lineages is still a matter of debate and research. LEVEL OF EVIDENCE: NA Laryngoscope, 134:1507-1516, 2024.

Economic Incentives in the Socially Optimal Management of Infectious Disease: When [Formula: see text] is Not Enough.

Does society benefit from encouraging or discouraging private infectious disease-risk mitigation? Private individuals routinely mitigate infectious disease risks through the adoption of a range of precautions, from vaccination to changes in their contact with others. Such precautions have epidemiological consequences. Private disease-risk mitigation generally reduces both peak prevalence of symptomatic infection and the number of people who fall ill. At the same time, however, it can prolong an epidemic. A reduction in prevalence is socially beneficial. Prolongation of an epidemic is not. We find that for a large class of infectious diseases, private risk mitigation is socially suboptimal-either too low or too high. The social optimum requires either more or less private mitigation. Since private mitigation effort depends on the cost of mitigation and the cost of illness, interventions that change either of these costs may be used to alter mitigation decisions. We model the potential for instruments that affect the cost of illness to yield net social benefits. We find that where a disease is not very infectious or the duration of illness is short, it may be socially optimal to promote private mitigation effort by increasing the cost of illness. By contrast, where a disease is highly infectious or long lasting, it may be optimal to discourage private mitigation by reducing the cost of disease. Society would prefer a shorter, more intense, epidemic to a longer, less intense epidemic. There is, however, a region in parameter space where the relationship is more complicated. For moderately infectious diseases with medium infectious periods, the social optimum depends on interactions between prevalence and duration. Basic reproduction numbers are not sufficient to predict the social optimum.

Long-term outcome of surgically-treated habitual patellar dislocation in children with coexistent patella alta. Minimum follow-up of 11 years.

We retrospectively reviewed the operative treatment carried out between 1988 and 1994 of eight patients with habitual patellar dislocation. In four the condition was bilateral. All patients had recurrent dislocation with severe functional disability. The surgical technique involved distal advancement of the patella by complete mobilisation of the patellar tendon, lateral release and advancement of vastus medialis obliquus. The long-term results were assessed radiologically, clinically and functionally using the Lysholm knee score, by an independent observer. The mean age at operation was 10.3 years (7 to 14) with a mean follow-up of 13.5 years (11 to 16). One patient required revision. At the latest follow-up, all patellae were stable and knees functional with a mean Lysholm knee score of 98 points (95 to 100). In those aged younger than ten years at operation there was a statistically significant improvement in the sulcus angle at the latest follow-up (Student's t-test, p = 0.001). Two patients developed asymptomatic patella infera as a late complication. This technique offers a satisfactory treatment for the immature patient presenting with habitual patellar dislocation associated with patella alta. If performed early, we believe that remodelling of the shallow trochlea may occur, adding intrinsic patellofemoral stability.

[Results of resection for ductal adenocarcinoma of the pancreatic head]. / Résultats carcinologiques de l'exérèse chirurgicale du cancer glandulaire céphalique du pancréas.

INTRODUCTION: Pancreaticoduodenectomy (PD) is the only curative treatment for adenocarcinoma of the pancreatic head but is associated with a significant early morbidity and a poor long term survival. Therefore, its value is still debated. The aim of this study was to evaluate early and distant results of PD for pancreatic adenocarcinoma, and to identify prognostic factors. SUMMARY: Seventy-nine patients who underwent PD with curative intent for adenocarcinoma of the pancreatic head from 1982 to 2002 were studied retrospectively. The following data were evaluated: operative mortality, long-term survival, prognostic factors (through univariate and multivariate analysis), and characteristics of 5-year survivors. RESULTS: Mortality rate was 1.3%. Survival at 1, 3 and 5 years was 46%, 26% and 11%. The median survival was 12 months. The prognostic factors were the T stage (T.N.M. classification) and radicality of resection. After multivariate analysis, radicality of resection was the only independent prognostic factor. Five patients survived for more than 5 years. They did not differ of the other patients but none had positive margin or venous invasion. CONCLUSIONS: These results (low mortality, significant distant survival including some long term survivors) suggest that PD for pancreatic adenocarcinoma must be indicated in most low-risk patients. PD remains the only curative treatment allowing prolonged survival.

Heterodimerization between the glucocorticoid receptor and the unrelated DNA-binding protein, Xenopus glucocorticoid receptor accessory factor.

The adrenal steroid hormones, glucocorticoids, control many physiological responses to trauma, including elevated synthesis of fibrinogen, a major blood-clotting protein. Glucocorticoid regulation of the gamma-fibrinogen subunit gene in Xenopus laevis is mediated by a binding site for Xenopus glucocorticoid receptor accessory factor (XGRAF) and a contiguous glucocorticoid response element (GRE) half-site. Here, we characterize the protein:DNA complex formed by a cooperative interaction between XGRAF, GR, and the DNA. We demonstrate that the complex contains XGRAF by competition in a gel shift assay. The presence of GR is established by two criteria: 1) size dependence of the XGRAF:GR:DNA complex on the size of the GR component and 2) interference with complex formation by GR antibody. Cooperative binding of XGRAF and GR to the DNA was quantitated, showing that GR favors binding to XGRAF:DNA compared with free DNA by a factor of 30. The cooperative interaction between XGRAF and GR can occur on nicked DNA but is disrupted when 1 bp is inserted between the XGRAF binding site and half-GRE. Significantly, this loss of physical association in vitro correlates with loss of XGRAF amplification of GR activity in transiently transfected primary Xenopus hepatocytes. The simplest explanation for cooperativity between XGRAF and GR is formation of a DNA-bound heterodimer of these two proteins. This mechanism represents a new mode of transcriptional regulation in which GR and a nonreceptor protein form a heterodimer, with both partners contacting their specific DNA sites simultaneously.

Effect of chronic renal failure on the expression of erythropoietin message in a murine model.

The anemia of chronic renal failure (CRF) is largely due to decreased production of erythropoietin (EPO) by the kidney. A small amount of EPO also originates from extra-renal sources, and this would be expected to assume a more important role in maintaining erythropoiesis when renal production is impaired. In this study, we examined the production of EPO mRNA by RT-PCR in kidney, liver, and bone marrow tissues isolated from normal mice, mice rendered acutely anemic by phlebotomy, and from mice with surgically induced CRF. The induction of acute anemia results in an expected increase in the expression of EPO mRNA in renal and hepatic tissue. In contrast, while the expression of EPO mRNA was expectedly reduced in the kidney from CRF mice, it was completely absent in the liver of these same animals. EPO mRNA expression was also absent in the bone marrow in both states of acute anemia and CRF. These results show that CRF can directly or indirectly can suppress the extrarenal production of EPO by the liver and that this effect may further aggravate the anemia of CRF.

Cardiovascular effects of two new calcium antagonists, PY 108-068 and PN 200-110, in conscious spontaneously hypertensive rats.

1. The acute cardiovascular effects of PY 108-068 and PN 200-110 were studied by means of a computerized analysis of the intra-aortic blood pressure (BP) recorded continuously for 26 h in conscious unrestrained spontaneously hypertensive rats. Both compounds were studied at three doses (50, 100 and 200 micrograms kg-1) and each dose was administered intravenously 5 times (09 h 00 min, 14 h 00 min, 19 h 00 min, 24 h 00 min and 09 h 00 min). Baroreflex sensitivity was measured 1 h following the last injection. 2. The two compounds were found to induce rapid (3 min) and dose-dependent falls in BP. After the first administration, these decreases reached -20% and -35% for systolic BP (SBP) and diastolic BP (DBP) respectively with PY 108-068 (200 micrograms kg-1) and -25% and -45% for SBP and DBP respectively with PN 200-110 (200 micrograms kg-1). 3. The duration of the reduction in BP increased with the dose and was much longer for PN 200-110 (180 min for SBP) than for PY 108-068 (20 min for SBP). 4. A tachycardia was associated with the decrease in BP which did not differ at 200 micrograms kg-1 between PY 108-068 (+ 108 beats min-1) and PN 200-110 (+ 103 beats min-1). Baroreflex sensitivity was not significantly increased by either drug. 5. The 5 repeated injections of PY 108-068 and PN 200-110 evoked similar responses. 6. In conclusion, both compounds exhibited marked hypotensive properties. PN 200-110 appeared to be more suitable for further development since its effects were found to be greater and much longer lasting than those of PY 108-068.

Benzophenone photosensitization of 2'-deoxyguanosine: characterization of the 2R and 2S diastereoisomers of 1-(2-deoxy-beta-D-erythro-pentofuranosyl)- 2-methoxy-4,5-imidazolidinedione. A model system for the investigation of photosensitized formation of DNA-protein crosslinks.

Benzophenone-mediated photosensitization of 2'-deoxyguanosine and its 3',5'-di-O-acetyl derivative, used as DNA model compounds, in oxygen-saturated water-methanol (1:1) solution results in the nucleophilic addition of methanol to the guanine base. The resulting modified nucleosides have been isolated by reverse-phase high-performance liquid chromatography and characterized by extensive spectroscopic measurements including 13C and 1H nuclear magnetic resonance, fast atom bombardment mass spectrometry and circular dichroism as the 2R and 2S diastereoisomers of 1-(2-deoxy-beta-D-erythro-pentofuranosyl)-2-methoxy-4,5-imidazolinedione and their related 3',5'-di-O-acetyl derivates. Information concerning the absolute configuration of the two pairs of diastereoisomers was inferred from detailed nuclear Overhauser effect experiments. A reaction mechanism, involving guanine radical intermediates, is proposed to explain the generation of these new guanine photoproducts.

Adolescent cocaine and injection stress effects on the estrous cycle.

Chronic cocaine exposure during critical periods of development induces short- and long-term effects. During the pubertal period, the hypothalamic-pituitary-gonadal (HPG) axis undergoes many dynamic changes. The present study investigated whether chronic periadolescent cocaine alters reproductive maturity in the rat. Sixty female Long-Evans hooded rats were randomly assigned to one of three conditions (20 mg cocaine/kg/day, saline injected and uninjected), for dosing from postnatal day 21 (P21) through P60. Several indicators of reproductive maturation and functioning were assessed during and following treatment. Cocaine exposure had no effect on the onset of puberty or on the date of first ovulation. The number of proestrus-estrus transitions was significantly lower in cocaine-exposed females compared to uninjected females, but not compared to saline-injected controls. This reduction was observed during exposure to cocaine, as well as after the cessation of injections. During the dosing period, cocaine-exposed rats also exhibited a greater number of cycles that had no clear P-E transition than did UN subjects; this effect disappeared once injections stopped. These alterations suggest immediate, and possibly persisting, alterations in the control of ovulation after chronic cocaine exposure throughout adolescence. Interestingly, during the injection period, the saline-injected females had a significantly greater number of diestrus days compared to uninjected and cocaine-injected animals, as well as a lower proportion of regular 4- and 5-day cycles. These differences disappeared once injections stopped. These results suggest a stress-induced irregularity of the estrous cycle, possibly attenuated by cocaine and recoverable after exposure. The present findings indicate that the HPG axis is susceptible to short-term, and possibly to long-term, alterations induced by cocaine exposure throughout the adolescent period.

Surgical treatment of anterolateral rotatory instability. A follow-up study.

Anterolateral rotatory instability in 31 acutely injured knees and 31 chronically unstable knees was surgically stabilized with a previously unreported method of iliotibial band tenodesis. The anterior cruciate ligament was stretched, torn, or absent in all 62 knees. Thirty-one patients, 20 with acute injury and 11 with chronic instability, were reviewed at a minimum of 2 years. A meniscal tear was present in 80% of the acute and in 91% of the chronic injuries. The anterior cruciate ligament was repaired, in addition to the iliotibial band tenodesis in 16 of the 20 acute injuries; there was no difference in the overall results between those repaired and not repaired. The evaluation of the patients was based on four subjective criteria (including functional parameters) and five objective criteria. Ninety-three percent of the patients had returned to competitive or recreational athletic activities involving cutting or pivoting movements. Both subjective and objective results were excellent or good in 93.6% of the patients. These results, based on our evaluation, warrant continued use of this procedure, according to the prescribed indications and technique.

Management of fibular hemimelia: amputation or limb lengthening.

We reviewed retrospectively 22 patients (23 limb segments) with fibular hemimelia treated by amputation or limb lengthening to evaluate these methods of treatment. There were 12 boys and 10 girls, all with associated anomalies in the lower limbs. Twelve patients (13 limb segments) had early amputation and prosthetic fitting and ten had tibial lengthening using the Ilizarov technique. At the latest follow-up, the twelve patients who had amputation were functioning well and had few complications. The ten patients who had lengthening had suffered numerous complications, and all had needed either further corrective surgery or to wear braces or shoe-raises. Two of the ten lengthened limbs required late amputation for poor function or cosmesis. There were fewer hospital admissions, clinic visits, and periods of absence from school in the amputation group. Our findings suggest that amputation is a more effective method of management than limb-lengthening in severe fibular hemimelia. The Ilizarov method is an attractive alternative for selected patients, but its exact role is not yet established. One problem is that families often have unrealistic expectations of the surgical and prosthetic technology available and may refuse amputation when this has been recommended.

Characterization of Nuclear Polyhedrosis Viruses from Three Subspecies of Lambdina fiscellaria

The eastern hemlock looper (EHL), Lambdina fiscellaria fiscellaria, the western hemlock looper (WHL), L. fiscellaria lugubrosa, and the western oak looper (WOL), L. fiscellaria somniaria, are closely related insects that are pests in Canadian forests. We have used restriction endonuclease (REN) and Southern blot analyses to characterize DNA of nuclear polyhedrosis viruses (NPVs) isolated from each of the three subspecies of L. fiscellaria. REN analysis of EHL-NPV, WHL-NPV, and WOL-NPV DNAs revealed that they have nonidentical REN-banding patterns. NPV DNA extracted from WOL larvae collected from Douglas fir trees had a different REN pattern than NPV DNA extracted from WOL larvae collected from Garry oak trees. Hybridization of radiolabeled EHL-NPV genomic DNA revealed that the EHL- and WHL-NPVs share considerable DNA sequence similarity, as radiolabeled EHL-NPV DNA hybridized strongly with all WHL-NPV DNA bands. The EHL-NPV polyhedrin gene hybridized strongly with WHL-NPV DNA, but the hybridization patterns of the two NPVs were different. Very weak hybridization was detected between the EHL-NPV polyhedrin gene and DNAs of the two WOL-NPVs. Nucleotide sequence analysis revealed that the polyhedrin genes of EHL-NPV and WHL-NPV differ in sequence by only eight nucleotide substitutions (five third position and three second position changes, resulting in four amino acid substitutions). Phlyogeneitc analysis using the polyhedrin genes of EHL-NPV and WHL-NPV indicate that these two viruses cluster with the Group II NPVs as described by Zanotto, Kessing, and Maruniak (1993, J. Invertebr. Pathol. 62, 147).

Learning through simulation: the next dimension in quality improvement.

Simulation modeling offers several distinct gains in learning opportunities beyond traditional quality improvement tools. A simulation model captures complex, multivariate system components and replicates system operation in compressed time. The visual aspect enables workers to "see" the effect of proposed changes and thus eliminates much of the fear of failure typically associated with change. Most important, simulation permits design of a total solution, addressing interactions of all system components.

[Risks and median-term results of aortic valve replacement for calcifying aortic stenosis in 100 patients more than 70 years old]. / Risques et résultats à moyen terme du remplacement valvulaire aortique pour sténose calcifiée chez 100 sujets de plus de 70 ans.

100 patients with poorly tolerated calcific aortic stenosis underwent aortic valve replacement by the same surgical team (Starr-Edwards prosthesis: 52 cases, Bjäork prosthesis: 43 cases, Lillehei-Kaster prosthesis: 2 cases, and Hancock bioprosthesis: 3 cases) between July 1971 and April 1978. The hospital mortality was 17% and acute pulmonary oedema and cardiomegaly were poor preoperative prognostic factors. The late mortality was 14.5% with an average follow-up period of 25 months (range: 2 to 74 months). The survival rate expressed as an actuarial graph was 63.1 +/- 4% at 4 years. 90% of the patients operated move up at least one class in the New York Heart Association classification and 2/3 return to Stage I. The cardiothoracic ratio improved from 0.58 +/- 0.06 to 0.51 +/- 0.03 (p less than 0.02) and the Soko low-Lyon index from 40 +/- 13 to 25 +/- 6 (p less than 0.001). The main complication encountered at middle term was haemorrhage, observed in 17.5% patients. Comparison of the spontaneous outcome of the disease with the results of surgery favour surgical treatment of patients over 70 years old with poorly tolerated calcific aortic stenosis. The valve of choice should be the bioprosthesis when dependance on anticoagulant therapy and the associated risks of haemorrhage are taken into consideration.

[Physiological variations of arterial pressure and heart rate in the first 5 minutes after moving from a supine to an upright position]. / Variations physiologiques de la pression artérielle et de la fréquence cardiaque dans les cinq premières minutes qui suivent le passage de la position couchée à la position debout.

The physiological variations of blood pressure and heart rate were studied in the first five minutes of orthostatism in conditions identical to those encountered in clinical medicine. An increase in heart rate and diastolic blood pressure was observed from the first minute. The value of systolic blood pressure decreased as the subject got up and then rose to the value measured when lying down. At the fourth and fifth minute the three parameters were stable at significantly higher values than observed when lying down for the heart rate and diastolic blood pressure, but at an identical level for the systolic blood pressure. This study shows the necessity of measuring the orthostatic blood pressure using a precise technique which detects postural abnormalities when measured in the minute of orthostatism and which gives an assessment of the standing blood pressure when measured at the fifth minute.

[Evaluation of an automatic device for arterial blood pressure determination : the Arteriosonde 1217]. / Evaluation d'un appareil automatique de la pression artérielle, l'Artériosonde 1217.

The reproductibility and reliability of measurements made with an automatic device for measuring blood pressure was assessed with reference to the results obtained by indirect auscultation with a mercury manometer. The results of the study of the average values of the correlation between successive values, and of the variability of the values of the systolic and diastolic blood pressure show that the measurement obtained by this method are very reproducible.

[Automatic measure of arterial pressure using the oscillometric method (Dynamap 845)]. / Mesure automatique de la pression artérielle par méthode oscillométrique (Dynamap 845).

The reproducibility and reliability of measurements performed with an automatic blood pressure measuring device based on the oscillometric method were assessed by comparison with the results obtained by the indirect auscultation using a mercury manometer. The results of the mean values, of the correlation between successive values and of the variation of the values of systolic and diastolic blood pressure show that the readings obtained by the automatic method are very reproducible.