Looking beyond the ovary for oncofertility care in women: uterine injury as a potential target for fertility-preserving treatments.

Treatment for cancer has the potential to significantly diminish fertility and, further, to negatively impact the obstetrical outcomes of pregnancies that do occur. Cancer survivors have decreased rates of fertility and increased rates of pregnancy complications, such as preterm birth and low birth weight, after exposure to chemotherapy. To date, research on the impact of chemotherapy and radiotherapy on fertility and pregnancy outcomes has focused largely on the gonadotoxic effect of cancer treatments on ovaries, while the uterus and endometrium have not been extensively studied. It is intuitive, however, that decreased fertility and poorer obstetrical outcomes may be substantially mediated through injury to a highly mitotic tissue like the endometrium, which is also central to embryo implantation and utero-placental exchange. Pregnancy complications in cancer survivors might be due to compromised blood supply to the endometrium and myometrium affecting placentation or altered remodeling of the pregnant uterus secondary to radiation fibrosis. Alterations in endometrial receptivity at the molecular level could affect pregnancy implantation and early pregnancy loss, but later complications also can occur. This review focuses on understanding the unintended effects of chemotherapy and radiotherapy on uterine function in female cancer survivors and the impact on pregnancy, and summarizes mechanisms to protect and treat the uterus before and after cancer chemotherapy and radiotherapy.

Antral follicle count recovery in women with menses after treatment with and without gonadotropin-releasing hormone agonist use during chemotherapy for breast cancer.

PURPOSE: After chemotherapy for breast cancer, most women will recover some ovarian function, but the timing and extent of this recovery are poorly understood. We studied post-chemotherapy ovarian recovery in women with and without a history of ovarian suppression during chemotherapy. METHODS: Reproductive age breast cancer patients who were seen prior to chemotherapy for fertility preservation consult were consented for follow-up ovarian function assessment (every 3-6 months after chemotherapy) with antral follicle count (AFC) in this prospective cohort study. We restricted our analysis to those with menses present after chemotherapy. Box plots were used to demonstrate the change in follow-up AFC versus time elapsed after chemotherapy. A mixed effects regression model was used to assess differences in AFC. RESULTS: Eighty-eight patients with a history of newly diagnosed breast cancer were included. Forty-five patients (51%) had ovarian suppression with GnRH agonist (GnRHa) during chemotherapy. AFC recovery appeared to plateau at 1 year after completing chemotherapy at a median of 40% of pre-chemotherapy AFC. After adjustment for age, initial AFC, cyclophosphamide exposure, combined hormonal contraceptive (CHC) use, and tamoxifen use, AFC recovered faster and to a greater degree for those women who underwent GnRHa therapy for ovarian protection during chemotherapy (P = 0.032). CONCLUSIONS: Women with menses after chemotherapy for breast cancer appear to recover their full potential AFC 1 year after their last chemotherapy dose. Treatment with GnRHa during chemotherapy is associated with a higher degree of AFC recovery. The findings of this study can aid in counseling patients prior to chemotherapy about expectations for ovarian recovery and planning post-treatment fertility preservation care to maximize reproductive potential when pre-treatment fertility preservation care is not possible or has limited oocyte yield.

The role of in-depth reproductive health counseling in addressing reproductive health concerns in female survivors of nongynecologic cancers.

The purpose of this study was to characterize reproductive concerns among female cancer survivors and determine the role of targeted counseling in improving overall reproductive quality of life (QOL). A survey was administered to women from the California Cancer Registry, ages 18-40, with nongynecologic cancers diagnosed from 1993 to 2007, who received fertility-compromising treatments. In total, 356 women completed the survey, which included questions regarding their reproductive health counseling history and the reproductive concerns scale (RCS), a validated reproductive QOL tool. Factors independently associated with higher RCS scores included a desire for children at the time of diagnosis, posttreatment infertility, treatment with chemoradiation or bone marrow transplant, and income less than $100,000 per year at diagnosis. Among the highest reported reproductive concerns were those related to loss of control over one's reproductive future and concerns about the effect of illness on one's future fertility. Across our population and independent of age, in-depth reproductive health counseling prior to cancer treatment was associated with significantly lower RCS scores. Our findings highlight the importance of early counseling and targeting high-risk groups for additional counseling after completion of cancer treatment. This approach may be an effective strategy for optimizing long-term reproductive QOL in this vulnerable population.

Physicochemical characterization of D-mannitol polymorphs: the challenging surface energy determination by inverse gas chromatography in the infinite dilution region.

Nowadays, it is well known that surface interactions play a preponderant role in mechanical operations, which are fundamental in pharmaceutical processing and formulation. Nevertheless, it is difficult to correlate surface behaviour in processes to physical properties measurement. Indeed, most pharmaceutical solids have multiple surface energies because of varying forms, crystal faces and impurities contents or physical defects, among others. In this paper, D-mannitol polymorphs (α, ß and δ) were studied through different characterization techniques highlighting bulk and surface behaviour differences. Due to the low adsorption behaviour of ß and δ polymorphs, special emphasis has been paid to surface energy analysis by inverse gas chromatography, IGC. Surface energy behaviour has been studied in Henry's domain showing that, for some organic solids, the classical IGC infinite dilution zone is never reached. IGC studies highlighted, without precedent in literature, dispersive surface energy differences between α and ß mannitol, with a most energetically active α form with a γ(s)(d) of 74.9 mJ·m⁻². Surface heterogeneity studies showed a highly heterogeneous α mannitol with a more homogeneous ß (40.0 mJ·m⁻²) and δ mannitol (40.3 mJ·m⁻²). Moreover, these last two forms behaved similarly considering surface energy at different probe concentrations.

[The daily public health nursing practice: the Montreal infectious diseases unit as an example]. / La pratique quotidienne des infirmières d'une direction de santé publique: l'exemple de l'unité maladies infectieuses à Montréal.

The health of urban populations depends on multiple factors, among them access to health and social services. The Montreal Public Health Department (PHD) is part of such services, where a number of nurses are working within a multidisciplinary team. It is through the description of the work accomplished by the team for infectious diseases control and prevention, and the vignettes of real life events related to the follow-up of syphilis, tuberculosis and hepatitis A cases, as well as quarantined individual exposed to SARS that the authors want to illustrate the work of the urban public health nurses. The examples are preceded by a description of the socio-demographic characteristics of the city of Montreal, that influence health problems, and therefore nurses' work.

Scrotal sonography: a valuable tool in the evaluation of complications following inguinal hernia repair.

PURPOSE: The aim of this study was to determine the utility of scrotal sonography in the evaluation of patients with scrotal pain or swelling following inguinal hernia repair. METHODS: From our database, we identified patients who were referred for sonographic evaluation because of persistent scrotal pain or swelling after inguinal hernia repair between July 1994 and February 1996. Sonograms and medical charts were reviewed retrospectively. RESULTS: Eight patients were included in this study. Doppler sonography demonstrated evidence of testicular infarction in 2 patients and absence of intratesticular diastolic flow in 1 patient. Five patients had postoperative fluid collections with sonographically normal testes. CONCLUSIONS: Scrotal sonography can diagnose testicular infarction following hernia repair and distinguish postoperative fluid collections from recurrent hernias.

Characterization and expression of the mouse endonuclease G gene.

Endonuclease G (Endo G) is a nuclease of prokaryotic lineage found in the mitochondria of vertebrates that has been suggested to play a role in mitochondrial DNA (mtDNA) replication. We have isolated and sequenced the entire mouse endo G gene, determined the limits of the mRNA, and mapped the promoter region. The coding sequence of the single copy gene is interrupted by two introns and analysis of the transcripts does not support a model by which more than one Endo G isoform could be produced by alternative splicing. We have also characterized a full-length human Endo G cDNA and comparison at the protein level of the human, bovine, and murine nucleases indicates a high degree of conservation except in the respective mitochondrial targeting signals. Endo G is ubiquitously expressed and the steady-state levels of its mRNA vary by a factor greater than seven between different tissues. The relationship between the mtDNA copy number and Endo G mRNA levels is not strictly proportional but tissues richer in mtDNA have higher amounts of the mRNA and vice versa.

Duplex Doppler estimation of resistive index in arcuate arteries of sedated, normal female dogs: implications for use in the diagnosis of renal failure.

The resistive index (RI), an ultrasonographic method of evaluating intrarenal resistance to blood flow, may be used to aid in diagnosis of renal failure. Values for arcuate artery RI, expressed as mean +/- two standard deviations, were obtained in clinically normal female dogs sedated with atropine, acepromazine maleate, diazepam, and ketamine hydrochloride. No statistically significant differences were noted between the values for the right kidney (0.33 to 0.57) versus the left kidney (0.32 to 0.56); however, the values were statistically significantly lower than values reported for nonsedated, normal dogs.

Estimation of arcuate artery resistive index as a diagnostic tool for aminoglycoside-induced acute renal failure in dogs.

OBJECTIVE: To determine the potential clinical usefulness of duplex Doppler estimation of arcuate artery resistive index (a measure of intrarenal blood flow impedance) for diagnosis of aminoglycoside-induced nephrotoxicosis. ANIMALS: 30 adult, female, mixed-breed dogs, allotted to 3 groups of 10 dogs each as: toxic dosage of gentamicin, therapeutic dosage of gentamicin, and saline solution sham equivalent in volume to that of the toxic dosage of gentamicin. PROCEDURE: After baseline screening to establish normalcy (serum biochemical analysis, endogenous creatinine clearance determination, urinalysis, urine protein-to-creatinine ratio, urine culture, gray-scale sonography, and percutaneous ultrasound-guided renal biopsy), results of arcuate artery resistive index determination were compared with serum creatinine and urine specific gravity values on a Monday-Wednesday-Friday data collection schedule for 10 days. Endogenous creatinine clearance determination, ultrasound-guided renal biopsy, and urine culture were repeated at the end of data collection in all 3 groups. RESULTS: Significant differences in resistive index measurements were not observed, despite clinicopathologic and renal biopsy results compatible with severe acute tubular necrosis in dogs of the toxic dosage group. CONCLUSIONS: Duplex Doppler sonography of arcuate artery blood flow impedance, expressed as the resistive index, appears to have poor clinical usefulness as a diagnostic tool in this disorder. CLINICAL RELEVANCE: Normal arcuate artery resistive index values obtained in dogs for which aminoglycoside-induced nephrotoxicosis is suspected do not exclude the disorder. If abnormal arcuate artery resistive index values are obtained for such dogs, further evaluation for nephropathies other than aminoglycoside-induced nephrotoxicosis may be considered.

Gray-scale sonographic characterization of aminoglycoside-induced nephrotoxicosis in a canine model.

RATIONALE AND OBJECTIVES: The diagnostic usefulness of gray-scale sonography was evaluated in a canine model of aminoglycoside-induced nephrotoxicosis. METHODS: Sonography was performed before and during the onset and progression of nephrotoxicosis induced by administration of a toxic dosage of gentamicin. Subjective visualization of increased renal cortex echogenicity (IRCE) was objectified with digital image analysis methods. Results of both subjective and objective evaluation were correlated with clinicopathologic tests and renal cortex biopsy obtained concurrently. RESULTS: Subjective visualization of IRCE was associated with significant nephrotoxicosis and was superior to serum creatinine elevation in nephrotoxicity detection. Objective detection of IRCE improved nephrotoxicity detection sensitivity to that of increased urine enzymuria. CONCLUSIONS: Based on the above results, subjective visualization of IRCE in patients with aminoglycoside-induced nephrotoxicity may occur before azotemia and is suggestive of significant renal dysfunction; application of digital image analysis methods may lead to earlier sonographic recognition of nephrotoxicity.

Sonographic evaluation of acute intrascrotal pathology.

High-resolution, real-time sonography is commonly used for the evaluation of acute scrotal pathology. Pulsed and color Doppler techniques enhance diagnostic accuracy [1, 2]. However, extensive distortion of intrascrotal anatomy can occur with advanced inflammation, infarction, or trauma, leading to decreased specificity of the sonographic examination.

Duplex sonography after transjugular intrahepatic portosystemic shunts (TIPS): normal hemodynamic findings and efficacy in predicting shunt patency and stenosis.

OBJECTIVE: Portal hemodynamics are altered by placement of a transjugular intrahepatic portosystemic shunt (TIPS). Normal duplex sonographic findings after TIPS placement and hemodynamic alterations indicating shunt failure have not yet been well described. The purposes of this study were to determine normal hemodynamic changes on duplex sonography after TIPS placement and to assess the efficacy of duplex sonography in detecting shunt dysfunction. SUBJECTS AND METHODS: Forty patients underwent TIPS placement and were entered into a study that included routine sonographic evaluation and portal venography at regular intervals. Portal venography was also performed if shunt velocities on duplex sonography changed from the baseline, which raised the question of shunt stenosis or occlusion. The pre-TIPS duplex sonographic study included determination of patency, velocity, and flow direction in the main, right, and left portal veins and in the hepatic artery. Follow-up sonography included the pre-TIPS examination in addition to velocity determinations in three segments of the shunt. Correlation was made between 82 concurrent sonographic and portal venographic studies. RESULTS: High-velocity blood flow (mean peak velocity, 135-200 cm/sec) was consistently seen within patent, well-functioning shunts. Hepatic artery peak systolic velocities increased from 79 cm/sec before TIPS placement to 131 cm/sec after TIPS placement (p < .001). Main portal vein velocities increased from 21.8 cm/sec before TIPS placement to 41.5 cm/sec after TIPS placement (p < .001). When compared with portal venography, duplex sonography was 98% sensitive and 100% specific in predicting the presence of blood flow within the stent. Sonography was highly sensitive and specific for detecting stent stenosis. Final sonographic criteria for shunt stenosis in angiographically documented cases were low-velocity shunt flow (< or = 60 cm/sec) in the entire stent, or low-velocity shunt flow with an associated focal velocity elevation. CONCLUSION: Consistent changes in portal venous and hepatic arterial hemodynamics are normally seen on duplex sonography after placement of a TIPS. Duplex sonography accurately predicts shunt patency and dysfunction when compared with portal venography. Duplex sonography is an effective, noninvasive method of evaluating shunt function and should be considered for use as the primary imaging technique in routine follow-up after TIPS placement.

Arteriohepatic dysplasia (Alagille's syndrome): unusual hepatic architecture and function.

BACKGROUND: Alagille's syndrome, also called arteriohepatic dysplasia, is a congenital anomaly consisting of hepatic, ocular, skeletal, and cardiac anomalies. The abdominal imaging findings were reviewed in eight patients with biopsy-proven Alagille's syndrome. One patient also had coexistent hepatocellular carcinoma. METHODS: Seven right upper quadrant sonograms, six hepatic CT studies, five hepatobiliary imaging studies, two hepatic MRI examinations, and two sulphur colloid liver spleen radionuclide studies were reviewed. RESULTS: The most striking abnormality was gross distortion of hepatic architecture. Five patients (63%) had marked external hepatic contour abnormalities, usually with either the entire liver or lobe having a predominately spherical shape. The portal vein was displaced by the spherical parenchymal component in four cases. Three other patients demonstrated marked hepatomegaly with no external contour abnormality. Hepatobiliary imaging studies demonstrated markedly prolonged excretion of the radiopharmaceutical in three of four patients examined. CONCLUSIONS: A diagnosis of Alagile's syndrome is suggested when a large, deformed and somewhat spherical liver is encountered, especially when hepatobiliary imaging studies demonstrate delayed excretion of radiopharmaceutical.

Endothelium-dependent vasodilation of peripheral conduit arteries in patients with heart failure.

Endothelium-dependent vasodilation of peripheral resistance vessels is abnormal in patients with heart failure, but there are little in vivo data on endothelium-dependent vasodilation of peripheral conduit vessels. This study assessed endothelium-dependent vasodilation of forearm conduit and resistance vessels in normal subjects and patients with heart failure. The effects of intraarterial endothelium-dependent and endothelium-independent vasodilators on both forearm conduit (brachial artery) and resistance vessels were assessed in 9 patients with New York Heart Association class II-III heart failure and 11 normal subjects of similar age. Brachial artery diameter was measured by two-dimensional, moderate-frequency (8 MHz) ultrasound, and forearm blood flow was measured by strain gauge plethysmography. The endothelium-dependent vasodilator, methacholine (0.3 and 1.5 micrograms/min), increased brachial artery diameter by 7.6 +/- 1.3% and 12.2 +/- 1.5% in normal subjects as compared to 6.9 +/- 2.1% and 10.4 +/- 2.4% in patients with heart failure (P = NS, normal vs heart failure). The endothelium-independent vasodilator, nitroglycerin (0.15 microgram), also produced similar increases in brachial artery diameter in the two groups (8.2 +/- 1.3% in normal subjects vs 11.1 +/- 1.4% in patients with heart failure, P = NS). In contrast, forearm blood flow responses to methacholine were significantly (P < .05) greater in normal subjects (4.1 +/- 0.5 and 9.2 +/- 1.4 mL/min/100 mL forearm volume) than in patients with heart failure (2.0 +/- 0.8 and 5.1 +/- 1.3 mL/min/100 mL forearm volume). Forearm blood flow responses to the endothelium-independent vasodilator, sodium nitroprusside, were similar between the two groups. This study suggests that endothelium-dependent and endothelium-independent vasodilation of the brachial artery is not impaired in patients with class II-III heart failure. This finding contrasts with abnormal endothelium-dependent vasodilation of forearm resistance vessels. These data suggest that there are regional differences in endothelial function in patients with heart failure.

Color Doppler sonography of transjugular intrahepatic portosystemic shunts (TIPS).

Transjugular intrahepatic portosystemic shunts (TIPS) have largely replaced surgically created shunts in the treatment of life-threatening sequelae of portal venous hypertension [1-5]. Conventional duplex and color Doppler sonography are proving to be useful tools in the assessment of the stents and their associated hemodynamic changes [2-5]. A thorough Doppler survey before and immediately after TIPS placement provides a baseline for evaluation of shunt function and procedure-related complications. Routine follow-up studies at regular intervals after the procedure provide noninvasive assessment of shunt patency and late complications. This pictorial essay illustrates the anatomic and hemodynamic abnormalities present with portal hypertension before TIPS and discusses the expected duplex and color Doppler findings after TIPS. The sonographic characteristics of immediate and delayed complications, as well as potential diagnostic pitfalls, are discussed.

Duplex and color Doppler sonography of complications after percutaneous interventional vascular procedures.

Duplex and color Doppler sonography have proved to be excellent noninvasive modalities for evaluating complications of percutaneous interventional vascular procedures. Complications including hematoma, pseudoaneurysm, arteriovenous fistula, thrombosis, stenosis, and vessel occlusion are routinely diagnosed with Doppler sonography. Hematomas exhibit variable echogenicity and internal complexity but never demonstrate internal blood flow. A pseudoaneurysm is a contained extravasation of blood that, unlike a hematoma, maintains a patent vascular connection with the injured vessel. Puncture-related arteriovenous fistulas are false vascular channels between an adjacent artery and vein that demonstrate low-resistance arterial signal, high-velocity venous outflow, and variable flow patterns within themselves. Narrowing in a stent demonstrates high-velocity turbulent flow with conventional Doppler and color aliasing with color Doppler techniques. Thrombus can be seen directly as a mural-based or luminal defect; however, it is often alterations in color flow dynamics, waveform characteristics, and flow velocities that permit conclusive diagnosis. Early experience in evaluation of stent stenosis in patients with transjugular intrahepatic portosystemic shunts suggests that low-velocity shunt flow indicates stenosis, likely related to the presence of low-resistance collateral pathways. Familiarity with both the interventional procedures and their possible complications facilitates prompt diagnosis and treatment.

Surveillance of infrainguinal vein grafts with duplex sonography.

This review considers the relative roles of traditional noninvasive vascular tests and conventional duplex and color flow Doppler sonography in the surveillance of infrainguinal autologous vein grafts. The purpose of surveillance is to identify significant anatomic or flow abnormalities that predispose to thrombosis, but can be repaired before graft thrombosis occurs. Although a few authors believe that serial measurements of the ankle-brachial index and other noninvasive vascular tests can serve as the primary method of surveillance for infrainguinal grafts, most authors do not concur. After the first postoperative month, stenosis caused by intimal hyperplasia is the most common cause of graft failure, usually occurring within 18 months after placement. Duplex sonography is both highly sensitive and specific for detection of such stenoses. Specific duplex sonographic criteria have been established for grading of stenoses and for the diagnosis and classification of arteriovenous fistulas. A large body of evidence suggests that graft thrombosis can occur without prior warning symptoms and that long-term graft patency improves if the asymptomatic lesions detected with duplex sonography are repaired before symptoms develop.